Antioxidants

25 pages, 36389 KiB

Open AccessArticle

Carica papaya Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats

by Jeane Rebecca Roy, Coimbatore Sadagopan Janaki, Selvaraj Jayaraman, Vijayalakshmi Periyasamy, Thotakura Balaji, Madhavan Vijayamalathi and Vishnu Priya Veeraraghavan

Antioxidants 2022, 11(10), 2081; https://doi.org/10.3390/antiox11102081 - 21 Oct 2022

Cited by 12 | Viewed by 3795

Abstract

In the management of type 2 diabetes, oral antidiabetic drugs have several side effects, which in turn have led the pharmaceutical industry to search for good therapeutic, non-toxic and reliable drugs. Carica papaya (C. papaya) is one of several plants in nature that [...] Read more.

In the management of type 2 diabetes, oral antidiabetic drugs have several side effects, which in turn have led the pharmaceutical industry to search for good therapeutic, non-toxic and reliable drugs. Carica papaya (C. papaya) is one of several plants in nature that have been found to possess anti-diabetic properties. Despite studies being focused on the antidiabetic activity of C. papaya, the molecular mechanism against high fat diet induced insulin resistance is yet to be identified. The role of C. papaya was evaluated on insulin signaling molecules, such as the insulin receptor (IR) and glucose transporter-4 (GLUT4) in high fat, diet-streptozotocin induced type 2 diabetic rats, and analyzed the bioactive compounds of C. papaya against IR and GLUT4 via molecular docking and dynamics. The ethanolic extract of C. papaya leaves (600 mg/kg of body weight) was given daily to male wistar rats for 45 days and we observed the various biochemical parameters, gene expression analysis and histopathology of skeletal muscle. Molecular docking and dynamics were undertaken to understand the bioactive compounds with the greatest hit rate. C. papaya treatment was able to control blood glucose levels, the lipid profile and serum insulin, but it facilitated tissue antioxidant enzymes and IR and GLUT4 levels. The in-silico study showed that kaempferol, quercitin and transferulic acid were the top three ligands with the greatest hit rate against the protein targets. Our preliminary findings, for the first time, showed that C. papaya reinstates the glycemic effect in the diabetic skeletal muscle by accelerating the expression of IR and GLUT4. Full article

(This article belongs to the Special Issue Frontiers in Oxidative Stress and Metabolic Diseases)

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21 pages, 5387 KiB

Open AccessArticle

Mechanisms of Epithelial-Mesenchymal Transition and Prevention of Dispase-Induced PVR by Delivery of an Antioxidant αB Crystallin Peptide

by Iori Wada, Parameswaran G Sreekumar, Christine Spee, Andrew J MacKay, Michael Ip and Ram Kannan

Antioxidants 2022, 11(10), 2080; https://doi.org/10.3390/antiox11102080 - 21 Oct 2022

Cited by 4 | Viewed by 2428

Abstract

Proliferative Vitreoretinopathy (PVR) is a refractory retinal disease whose primary pathogenesis involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. At present, there is no effective treatment other than surgery for PVR. The purpose of this study was to investigate the [...] Read more.

Proliferative Vitreoretinopathy (PVR) is a refractory retinal disease whose primary pathogenesis involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. At present, there is no effective treatment other than surgery for PVR. The purpose of this study was to investigate the effect of αB crystallin peptide (αBC-P) on EMT in PVR. We have previously shown that this peptide is antiapoptotic and regulates RPE redox status. Subconfluent primary human RPE (hRPE) cells were stimulated by TGFβ2 (10 ng/mL) with or without αBC-P (50 or 75 μg/mL) for 48 h and expression of EMT/mesenchymal to epithelial transition (MET) markers was determined. Mitochondrial ROS (mtROS) generation in hRPE cells treated with TGFβ2 was analyzed. The effect of TGFβ2 and αBC-P on oxidative phosphorylation (OXPHOS) and glycolysis in hRPE was studied. RPE cell migration was also assessed. A PVR-like phenotype was induced by intravitreal dispase injection in C57BL/6J mice. PVR progression and potential therapeutic efficiency of αBC-Elastin-like polypeptides (ELP) was studied using fundus photography, OCT imaging, ERG, and histologic analysis of the retina. αSMA, E-cadherin, Vimentin, Fibronectin and, RPE65, and CTGF were analyzed on Day 28. Additionally, the amount of VEGF-A in retinal cell lysates was measured. The EMT-associated αSMA, Vimentin, SNAIL and SLUG showed a significant upregulation with TGFβ2, and their expression was significantly suppressed by cotreatment with αBC-P. The MET-associated markers, E-cadherin and Sirt1, were significantly downregulated by TGFβ2 and were restored by αBC-P. Incubation of hRPE with TGFβ2 for 24 h showed a marked increase in mitochondrial ROS which was noticeably inhibited by αBC-ELP. We also showed that after TGFβ2 treatment, SMAD4 translocated to mitochondria which was blocked by αBC-ELP. Mitochondrial oxygen consumption rate increased with TGFβ2 treatment for 48 h, and αBC-P co-treatment caused a further increase in OCR. Glycolytic functions of RPE were significantly suppressed with αBC-P (75 μg/mL). In addition, αBC-P significantly inhibited the migration from TGFβ2 treatment in hRPE cells. The formation of proliferative membranes was suppressed in the αBC-ELP-treated group, as evidenced by fundus, OCT, and H&E staining in dispase-induced PVR in mice. Furthermore, ERG showed an improvement in c-wave amplitude. In addition, immunostaining showed significant suppression of αSMA and RPE65 expression. It was also observed that αBC-ELP significantly reduced the expression level of vimentin, fibronectin, and CTGF. Our findings suggest that the antioxidant αBC-P may have therapeutic potential in preventing PVR by reversing the phenotype of EMT/MET and improving the mitochondrial function in RPE cells. Full article

(This article belongs to the Special Issue Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Eye Diseases)

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12 pages, 925 KiB

Open AccessArticle

Oxidative Potential in Exhaled Air (OPEA) as a Tool for Predicting Certain Respiratory Disorders in the General Adult Population: Cross-Sectional Analysis Nested in the Swiss Health Study

by Irina Guseva Canu, Maud Hemmendinger, Antonio Toto, Pascal Wild, Caroline Veys-Takeuchi, Murielle Bochud and Guillaume Suárez

Antioxidants 2022, 11(10), 2079; https://doi.org/10.3390/antiox11102079 - 21 Oct 2022

Cited by 2 | Viewed by 1963

Abstract

In a pilot clinical study, OPEA allowed for distinguishing participants with and without chronic obstructive pulmonary disease. This study aimed to assess whether abnormal spirometry parameters and immunity against SARS-CoV-2 are associated with increased OPEA and estimating the OPEA reference interval. Swiss adult [...] Read more.

In a pilot clinical study, OPEA allowed for distinguishing participants with and without chronic obstructive pulmonary disease. This study aimed to assess whether abnormal spirometry parameters and immunity against SARS-CoV-2 are associated with increased OPEA and estimating the OPEA reference interval. Swiss adult residents of the Vaud Canton aged 20–69 years randomly selected from the Federal Statistical Office’s registries, speaking French or German, were included and examined between 1 October 2020 and 31 December 2021. General health status and presence of respiratory diseases were assessed by questionnaire and spirometry. Spirometric results were compared with the predicted values and their lower limits of norms of the Global Lung Function Initiative. SARS-CoV-2-seroprevalence was assessed using the Luminex-based test of IgG. Statistical analysis consisted of unilateral t-tests and ANOVA. Lower and upper limit of OPEA reference interval with associated 90%-confidence interval (90%CI) were estimated for the sub-sample of healthy adults by bootstrap, after excluding outliers. The study sample included 247 participants. SARS-CoV-2-seropositive participants and those with an obstructive syndrome had a significantly higher OPEA than seronegative and healthy participants. The estimated reference interval was: −0.0516 (90%CI = −0.0735; −0.0316); −0.0044 (90%CI = −0.0224; 0.0153). OPEA could predict inflammatory-based respiratory disorders, but needs further validation in different settings and for other pathologies. Full article

(This article belongs to the Special Issue Redox Regulation in Pulmonary Diseases)

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12 pages, 860 KiB

Open AccessReview

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

by Virgile Clergue-Duval, Laurent Coulbault, Frank Questel, Nicolas Cabé, Alice Laniepce, Clément Delage, Céline Boudehent, Vanessa Bloch, Shailendra Segobin, Mickael Naassila, Anne-Lise Pitel and Florence Vorspan

Antioxidants 2022, 11(10), 2078; https://doi.org/10.3390/antiox11102078 - 21 Oct 2022

Cited by 6 | Viewed by 5392

Abstract

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders [...] Read more.

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke’s encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments. Full article

(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease and the Role of Antioxidants)

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16 pages, 2975 KiB

Open AccessArticle

Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability

by Marilina Mascaró, Exequiel G. Alonso, Karen Schweitzer, Martín E. Rabassa, Jessica A. Carballido, Agustina Ibarra, Eliana N. Alonso, Vicente Bermúdez, Lucía Fernández Chavez, Georgina P. Coló, María Julia Ferronato, Pamela Pichel, Sergio Recio, Valentina Clemente, Maria Eugenia Fermento, María Marta Facchinetti and Alejandro C. Curino

Antioxidants 2022, 11(10), 2077; https://doi.org/10.3390/antiox11102077 - 21 Oct 2022

Cited by 2 | Viewed by 2107

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1. Full article

(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1 2022)

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20 pages, 1343 KiB

Open AccessArticle

Phytochemical Profile, Preliminary Toxicity, and Antioxidant Capacity of the Essential Oils of Myrciaria floribunda (H. West ex Willd.) O. Berg. and Myrcia sylvatica (G. Mey) DC. (Myrtaceae)

by Ângelo Antônio Barbosa de Moraes, Oberdan Oliveira Ferreira, Leonardo Souza da Costa, Lorena Queiroz Almeida, Everton Luiz Pompeu Varela, Márcia Moraes Cascaes, Celeste de Jesus Pereira Franco, Sandro Percário, Lidiane Diniz do Nascimento, Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade

Antioxidants 2022, 11(10), 2076; https://doi.org/10.3390/antiox11102076 - 21 Oct 2022

Cited by 19 | Viewed by 3453

Abstract

The essential oils (EOs) of Myrciaria floribunda (Mflo) and Myrcia sylvatica (Msyl) (Myrtaceae) were obtained by hydrodistillation. The analysis of volatile constituents was performed by GC/MS. Preliminary toxicity was assessed on Artemia salina Leach. The antioxidant capacity was measured by the ABTS^•+ [...] Read more.

The essential oils (EOs) of Myrciaria floribunda (Mflo) and Myrcia sylvatica (Msyl) (Myrtaceae) were obtained by hydrodistillation. The analysis of volatile constituents was performed by GC/MS. Preliminary toxicity was assessed on Artemia salina Leach. The antioxidant capacity was measured by the ABTS^•+ and DPPH^• radical inhibitory activities. The results indicate that the Mflo EO had the highest yield (1.02%), and its chemical profile was characterized by high levels of hydrocarbon (65.83%) and oxygenated (25.74%) monoterpenes, especially 1,8-cineole (23.30%), terpinolene (22.23%) and α-phellandrene (22.19%). Regarding the Msyl EO, only hydrocarbon (51.60%) and oxygenated (46.52%) sesquiterpenes were identified in the sample, with (Z)-α-trans-bergamotene (24.57%), α-sinensal (13.44%), and (Z)-α-bisabolene (8.33%) at higher levels. The EO of Mflo exhibited moderate toxicity against A. salina (LC₅₀ = 82.96 ± 5.20 µg.mL⁻¹), while the EO of Msyl was classified as highly toxic (LC₅₀ = 2.74 ± 0.50 µg.mL⁻¹). In addition, relative to Trolox, the EOs of Mflo and Msyl showed significant inhibitory effects (p < 0.0001) against the DPPH^• radical. This study contributes to the expansion of chemical and biological knowledge on the EOs of Myrtaceae species from the Amazon region. Full article

(This article belongs to the Special Issue Antioxidant Activity of Essential Oils)

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14 pages, 3617 KiB

Open AccessArticle

Comparative Study of Antiviral, Cytotoxic, Antioxidant Activities, Total Phenolic Profile and Chemical Content of Propolis Samples in Different Colors from Turkiye

by Nazli Boke Sarikahya, Ekin Varol, Gaye Sumer Okkali, Banu Yucel, Rodica Margaoan and Ayse Nalbantsoy

Antioxidants 2022, 11(10), 2075; https://doi.org/10.3390/antiox11102075 - 21 Oct 2022

Cited by 5 | Viewed by 2533

Abstract

Propolis is a valuable natural substance obtained by honey bees after being collected from the bark, resin of trees, plant leaves and mixed with their saliva, and has been widely used for various biological activities. The properties of propolis can vary widely by [...] Read more.

Propolis is a valuable natural substance obtained by honey bees after being collected from the bark, resin of trees, plant leaves and mixed with their saliva, and has been widely used for various biological activities. The properties of propolis can vary widely by botanical origin, location of the hives and colony population. It is thought that the color of propolis is one of the main factors determining its acceptability and originates from the flower markers, pollen and nectar of some plants and is directly related to its chemical content. It is important to compare and standardize the colors, chemical content and biological activities of propolis in our country, which has a rich endemic plant diversity. Thus, in this study, the color indexes of 39 propolis samples from different locations in Turkiye were determined by Lovibond Tintometer, for the first time. The color index, total phenolic content, cytotoxic and antioxidant activities relationship of propolis and two commercial propolis samples were also investigated by HCA and PCA. Turkish propolis, which is defined by its color indices, chemical contents and many different activity potentials, such as antioxidant, antiviral and cytotoxic activity, will find use in many fields from medicine to cosmetics with this study. Full article

(This article belongs to the Special Issue Antioxidant Activity of Honey Bee Products)

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38 pages, 2791 KiB

Open AccessReview

Natural Active Ingredients for Poly (Lactic Acid)-Based Materials: State of the Art and Perspectives

by Andrea Lombardi, Andrea Fochetti, Pamela Vignolini, Margherita Campo, Alessandra Durazzo, Massimo Lucarini, Debora Puglia, Francesca Luzi, Marco Papalini, Monia Renzi, Andrea Cavallo and Roberta Bernini

Antioxidants 2022, 11(10), 2074; https://doi.org/10.3390/antiox11102074 - 20 Oct 2022

Cited by 9 | Viewed by 3524

Abstract

This review describes the state of the art in the field of poly (lactic acid) (PLA)-based materials activated by natural compounds and extracts (active ingredients, AIs) from plant sources for food and biomedical applications. With a multidisciplinary approach, after a description of the [...] Read more.

This review describes the state of the art in the field of poly (lactic acid) (PLA)-based materials activated by natural compounds and extracts (active ingredients, AIs) from plant sources for food and biomedical applications. With a multidisciplinary approach, after a description of the synthesis and properties of PLA, special attention was paid to the chemical properties and unconventional extraction technologies of AIs used for PLA activation. Innovative techniques for the incorporation of AIs into PLA; characterization and the antioxidant and antimicrobial properties of the novel materials were discussed. In view of future perspectives, this study has evidenced that some aspects need to be further investigated from joint research between academia and industry, according to the green chemistry principles and circular economy strategy. Full article

(This article belongs to the Special Issue 10th Anniversary of Antioxidants—Review Collection)

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14 pages, 2966 KiB

Open AccessArticle

Effects of Hyperbaric Oxygen Preconditioning on Doxorubicin Cardiorespiratory Toxicity

by Vivian Doerr, Ryan N. Montalvo, Branden L. Nguyen, Franccesco P. Boeno, Michael D. Sunshine, Victoria E. Bindi, David D. Fuller and Ashley J. Smuder

Antioxidants 2022, 11(10), 2073; https://doi.org/10.3390/antiox11102073 - 20 Oct 2022

Cited by 3 | Viewed by 2495

Abstract

Cardiorespiratory dysfunction resulting from doxorubicin (DOX) chemotherapy treatment is a debilitating condition affecting cancer patient outcomes and quality of life. DOX treatment promotes cardiac and respiratory muscle pathology due to enhanced reactive oxygen species (ROS) production, mitochondrial dysfunction and impaired muscle contractility. In [...] Read more.

Cardiorespiratory dysfunction resulting from doxorubicin (DOX) chemotherapy treatment is a debilitating condition affecting cancer patient outcomes and quality of life. DOX treatment promotes cardiac and respiratory muscle pathology due to enhanced reactive oxygen species (ROS) production, mitochondrial dysfunction and impaired muscle contractility. In contrast, hyperbaric oxygen (HBO) therapy is considered a controlled oxidative stress that can evoke a substantial and sustained increase in muscle antioxidant expression. This HBO-induced increase in antioxidant capacity has the potential to improve cardiac and respiratory (i.e., diaphragm) muscle redox balance, preserving mitochondrial function and preventing muscle dysfunction. Therefore, we determined whether HBO therapy prior to DOX treatment is sufficient to enhance muscle antioxidant expression and preserve muscle redox balance and cardiorespiratory muscle function. To test this, adult female Sprague Dawley rats received HBO therapy (2 or 3 atmospheres absolute (ATA), 100% O₂, 1 h/day) for 5 consecutive days prior to acute DOX treatment (20 mg/kg i.p.). Our data demonstrate that 3 ATA HBO elicits a greater antioxidant response compared to 2 ATA HBO. However, these effects did not correspond with beneficial adaptations to cardiac systolic and diastolic function or diaphragm muscle force production in DOX treated rats. These findings suggest that modulating muscle antioxidant expression with HBO therapy is not sufficient to prevent DOX-induced cardiorespiratory dysfunction. Full article

(This article belongs to the Special Issue Redox Control of Cardiac and Skeletal Muscle Function II)

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19 pages, 15018 KiB

Open AccessArticle

Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro

by Yan-Ning Chen, Chieh-Kai Chan, Ching-Yu Yen, Jun-Ping Shiau, Meng-Yang Chang, Cheng-Chung Wang, Jiiang-Huei Jeng, Jen-Yang Tang and Hsueh-Wei Chang

Antioxidants 2022, 11(10), 2072; https://doi.org/10.3390/antiox11102072 - 20 Oct 2022

Cited by 5 | Viewed by 1744

Abstract

A novel nitrated [6,6,6]tricycles-derived compound containing nitro, methoxy, and ispropyloxy groups, namely SK1, was developed in our previous report. However, the anticancer effects of SK1 were not assessed. Moreover, SK1 contains two nitro groups (NO₂) and one nitrogen-oxygen (N-O) bond exhibiting [...] Read more.

A novel nitrated [6,6,6]tricycles-derived compound containing nitro, methoxy, and ispropyloxy groups, namely SK1, was developed in our previous report. However, the anticancer effects of SK1 were not assessed. Moreover, SK1 contains two nitro groups (NO₂) and one nitrogen-oxygen (N-O) bond exhibiting the potential for oxidative stress generation, but this was not examined. The present study aimed to evaluate the antiproliferation effects and oxidative stress and its associated responses between oral cancer and normal cells. Based on the MTS assay, SK1 demonstrated more antiproliferation ability in oral cancer cells than normal cells, reversed by N-acetylcysteine. This suggests that SK1 causes antiproliferation effects preferentially in an oxidative stress-dependent manner. The oxidative stress-associated responses were further validated, showing higher ROS/MitoSOX burst, MMP, and GSH depletion in oral cancer cells than in normal cells. Meanwhile, SK1 caused oxidative stress-causing apoptosis, such as caspases 3/8/9, and DNA damages, such as γH2AX and 8-OHdG, to a greater extent in oral cancer cells than in normal cells. Siilar to cell viability, these oxidative stress responses were partially diminished by NAC, indicating that SK1 promoted oxidative stress-dependent responses. In conclusion, SK1 exerts oxidative stress, apoptosis, and DNA damage to a greater extent to oral cancer cells than in normal cells. Full article

(This article belongs to the Special Issue Mitochondrial Oxidative and Nitrosative Stress as a Therapeutic Target in Diseases II)

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17 pages, 23425 KiB

Open AccessReview

Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants

by Samukelisiwe C. Shabalala, Rabia Johnson, Albertus K. Basson, Khanyisani Ziqubu, Nokulunga Hlengwa, Sinenhlanhla X. H. Mthembu, Sihle E. Mabhida, Sithandiwe E. Mazibuko-Mbeje, Sidney Hanser, Ilenia Cirilli, Luca Tiano and Phiwayinkosi V. Dludla

Antioxidants 2022, 11(10), 2071; https://doi.org/10.3390/antiox11102071 - 20 Oct 2022

Cited by 34 | Viewed by 4714

Abstract

Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density [...] Read more.

Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q₁₀, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E. Full article

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18 pages, 333 KiB

Open AccessArticle

Effects of Dietary Vitamin E Supplementation on Reproductive Performance, Egg Characteristics, Antioxidant Capacity, and Immune Status in Breeding Geese during the Late Laying Period

by Zhenming Fu, Tao Zhong, Xiaoli Wan, Lei Xu, Haiming Yang, Houming Han and Zhiyue Wang

Antioxidants 2022, 11(10), 2070; https://doi.org/10.3390/antiox11102070 - 20 Oct 2022

Cited by 10 | Viewed by 2650

Abstract

This study aimed to tentatively evaluate the effects of dietary vitamin E (VE) on goose reproductive physiology through the investigation of reproductive performance, egg characteristics, antioxidant capacity, and immune status in breeding geese. A total of 480 female and 96 male Jiangnan White [...] Read more.

This study aimed to tentatively evaluate the effects of dietary vitamin E (VE) on goose reproductive physiology through the investigation of reproductive performance, egg characteristics, antioxidant capacity, and immune status in breeding geese. A total of 480 female and 96 male Jiangnan White breeding geese were randomly assigned to four treatments with four replicates, and each replicate had 30 females and six males. Four levels of VE were successively added to four treatment diets from 48 to 54 weeks of age, representing the effects of VE deficiency (0 IU/kg), basic-dose VE (40 IU/kg), middle-dose VE (200 IU/kg), and high-dose VE (2000 IU/kg). Neither the egg-laying rate nor the healthy-gosling rate were affected by any of the VE supplementations (p > 0.05). The qualified egg rate, hatchability of fertilized eggs, and spleen index were increased by each VE supplementation (p < 0.05). Egg fertility, the concentration of plasma reproductive hormones (i.e., the follicle-stimulating hormone, estradiol, and progesterone), follicular development, and antioxidant enzyme activities—i.e., the concentration of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)—in the liver and ovary were improved by 200 IU/kg of dietary VE (p < 0.05). Plasma VE concentration, immunoglobulin A, and immunoglobulin G content were increased, whereas plasma vitamin D₃ concentration was reduced by increasing dietary VE levels to 2000 IU/kg (p < 0.05). The VE deposition of yolk, the yolk color depth, and the albumen rate were increased by each VE supplementation (p < 0.05). Antioxidant enzyme activities (i.e., MDA concentration, T-AOC, SOD, and GSH) in yolk were improved by 200 IU/kg and 2000 IU/kg of dietary VE (p < 0.05), compared with 0 IU/kg. The VE deposition was significantly correlated with GSH activity and the MDA concentration in egg yolk (p < 0.05). However, the high intake of dietary VE (2000 IU/kg vs. 200 IU/kg) decreased egg fertility (p < 0.05) and reduced the antioxidant capacity in the liver and ovary (p < 0.05). The qualified egg rate was positively correlated to immunoglobulin production (p < 0.05). Egg fertility and hatchability were correlatively improved by increased antioxidant enzyme activity; decreased MDA in the liver and ovary; hatchability; and enhanced immune status (p < 0.05). To sum up, both VE deficiency and high-dose VE (2000 IU/kg) reduced reproductive performance, whereas a dose of 200 IU/kg VE achieved optimal fertility, possibly through enhancing antioxidant capacity and immune status. Full article

30 pages, 8743 KiB

Open AccessArticle

Is Caperatic Acid the Only Compound Responsible for Activity of Lichen Platismatia glauca within the Nervous System?

by Elżbieta Studzińska-Sroka, Aleksandra Majchrzak-Celińska, Monika Bańdurska, Natalia Rosiak, Dominik Szwajgier, Ewa Baranowska-Wójcik, Marcin Szymański, Wojciech Gruszka and Judyta Cielecka-Piontek

Antioxidants 2022, 11(10), 2069; https://doi.org/10.3390/antiox11102069 - 20 Oct 2022

Cited by 14 | Viewed by 2820

Abstract

Lichens are a source of various biologically active compounds. However, the knowledge about them is still scarce, and their use in medicine is limited. This study aimed to investigate the therapeutic potential of the lichen Platismatia glauca and its major metabolite caperatic acid [...] Read more.

Lichens are a source of various biologically active compounds. However, the knowledge about them is still scarce, and their use in medicine is limited. This study aimed to investigate the therapeutic potential of the lichen Platismatia glauca and its major metabolite caperatic acid in regard to their potential application in the treatment of central nervous system diseases, especially neurodegenerative diseases and brain tumours, such as glioblastoma. First, we performed the phytochemical analysis of the tested P. glauca extracts based on FT-IR derivative spectroscopic and gas chromatographic results. Next the antioxidant properties were determined, and moderate anti-radical activity, strong chelating properties of Cu²⁺ and Fe²⁺ ions, and a mild effect on the antioxidant enzymes of the tested extracts and caperatic acid were proved. Subsequently, the influence of the tested extracts and caperatic acid on cholinergic transmission was determined by in vitro and in silico studies confirming that inhibitory effect on butyrylcholinesterase is stronger than against acetylcholinesterase. We also confirmed the anti-inflammatory properties of P. glauca extracts and caperatic acid using a COX-2 and hyaluronidase inhibition models. Moreover, our studies show the cytotoxic and pro-apoptotic activity of the P. glauca extracts against T98G and U-138 MG glioblastoma multiforme cell lines. In conclusion, it is possible to assume that P. glauca extracts and especially caperatic acid can be regarded as the source of the valuable substances to finding new therapies of central nervous system diseases. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Bioactive Plant Compounds for Therapeutic Purpose)

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16 pages, 3592 KiB

Open AccessArticle

Folic Acid Improves Parkin-Null Drosophila Phenotypes and Transiently Reduces Vulnerable Dopaminergic Neuron Mitochondrial Hydrogen Peroxide Levels and Glutathione Redox Equilibrium

by Katherine L. Houlihan, Petros P. Keoseyan, Amber N. Juba, Tigran Margaryan, Max E. Voss, Alexander M. Babaoghli, Justin M. Norris, Greg J. Adrian, Artak Tovmasyan and Lori M. Buhlman

Antioxidants 2022, 11(10), 2068; https://doi.org/10.3390/antiox11102068 - 20 Oct 2022

Cited by 3 | Viewed by 2252

Abstract

Loss-of-function parkin mutations cause oxidative stress and degeneration of dopaminergic neurons in the substantia nigra. Several consequences of parkin mutations have been described; to what degree they contribute to selective neurodegeneration remains unclear. Specific factors initiating excessive reactive oxygen species production, inefficient antioxidant [...] Read more.

Loss-of-function parkin mutations cause oxidative stress and degeneration of dopaminergic neurons in the substantia nigra. Several consequences of parkin mutations have been described; to what degree they contribute to selective neurodegeneration remains unclear. Specific factors initiating excessive reactive oxygen species production, inefficient antioxidant capacity, or a combination are elusive. Identifying key oxidative stress contributors could inform targeted therapy. The absence of Drosophila parkin causes selective degeneration of a dopaminergic neuron cluster that is functionally homologous to the substantia nigra. By comparing observations in these to similar non-degenerating neurons, we may begin to understand mechanisms by which parkin loss of function causes selective degeneration. Using mitochondrially targeted redox-sensitive GFP2 fused with redox enzymes, we observed a sustained increased mitochondrial hydrogen peroxide levels in vulnerable dopaminergic neurons of parkin-null flies. Only transient increases in hydrogen peroxide were observed in similar but non-degenerating neurons. Glutathione redox equilibrium is preferentially dysregulated in vulnerable neuron mitochondria. To shed light on whether dysregulated glutathione redox equilibrium primarily contributes to oxidative stress, we supplemented food with folic acid, which can increase cysteine and glutathione levels. Folic acid improved survival, climbing, and transiently decreased hydrogen peroxide and glutathione redox equilibrium but did not mitigate whole-brain oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurological and Neurodegenerative Disorders)

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15 pages, 1137 KiB

Open AccessReview

The Nrf2 in Obesity: A Friend or Foe?

by Yudong Xia, Xiaoying Zhai, Yanning Qiu, Xuemei Lu and Yi Jiao

Antioxidants 2022, 11(10), 2067; https://doi.org/10.3390/antiox11102067 - 20 Oct 2022

Cited by 15 | Viewed by 3883

Abstract

Obesity and its complications have become serious global health concerns recently and increasing work has been carried out to explicate the underlying mechanism of the disease development. The recognized correlations suggest oxidative stress and inflammation in expanding adipose tissue with excessive fat accumulation [...] Read more.

Obesity and its complications have become serious global health concerns recently and increasing work has been carried out to explicate the underlying mechanism of the disease development. The recognized correlations suggest oxidative stress and inflammation in expanding adipose tissue with excessive fat accumulation play important roles in the pathogenesis of obesity, as well as its associated metabolic syndromes. In adipose tissue, obesity-mediated insulin resistance strongly correlates with increased oxidative stress and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been described as a key modulator of antioxidant signaling, which regulates the transcription of various genes coding antioxidant enzymes and cytoprotective proteins. Furthermore, an increasing number of studies have demonstrated that Nrf2 is a pivotal target of obesity and its related metabolic disorders. However, its effects are controversial and even contradictory. This review aims to clarify the complicated interplay among Nrf2, oxidative stress, lipid metabolism, insulin signaling and chronic inflammation in obesity. Elucidating the implications of Nrf2 modulation on obesity would provide novel insights for potential therapeutic approaches in obesity and its comorbidities. Full article

(This article belongs to the Special Issue Molecular Targets of Oxidative Stress: Focus on the Nrf2 Signaling Pathway in Health and Disease)

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15 pages, 656 KiB

Open AccessArticle

Phytobiotics from Oregano Extracts Enhance the Intestinal Health and Growth Performance of Pigs

by Marcos Elias Duarte and Sung Woo Kim

Antioxidants 2022, 11(10), 2066; https://doi.org/10.3390/antiox11102066 - 20 Oct 2022

Cited by 12 | Viewed by 3220

Abstract

This study aimed to investigate the effects of phytobiotics on the intestinal health and growth performance of pigs. Totals of 40 newly-weaned pigs with 6.4 ± 0.3 kg BW (Exp. 1) and 120 growing pigs with 27.9 ± 2.3 kg BW (Exp. 2) [...] Read more.

This study aimed to investigate the effects of phytobiotics on the intestinal health and growth performance of pigs. Totals of 40 newly-weaned pigs with 6.4 ± 0.3 kg BW (Exp. 1) and 120 growing pigs with 27.9 ± 2.3 kg BW (Exp. 2) were allotted in RCBD in a 2 × 2 factorial arrangement. The factors were: antibiotics as growth promoter (AGP) and phytobiotics (PHY). Pigs were fed experimental diets during 21 d (Exp. 1) and 42 d (Exp. 2). Growth performance, health parameters, and nutrient digestibility were evaluated. In Exp. 1, AGP diet increased (p < 0.05) ADG and G:F compared with a diet without AGP or PHY and a diet with AGP combined with PHY. PHY decreased (p < 0.05) TNF-α and IgG in the jejunum and protein carbonyl in plasma, whereas it increased (p < 0.05) the villus height. In Exp. 2, AGP or PHY diets increased (p < 0.05) ADG, ADFI, and G:F compared with a diet without AGP or PHY and a diet with AGP combined with PHY. PHY decreased (p < 0.05) IgG and PC in plasma. Collectively, AGP and PHY improved growth performance by reducing oxidative stress and enhancing immune status and jejunal morphology. However, the combinational use of phytobiotics with antibiotics suppressed their effect. Full article

(This article belongs to the Special Issue Oxidative Stress, Reactive Oxygen Species and Animal Nutrition)

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17 pages, 4018 KiB

Open AccessArticle

Determination of Redox Status in Different Tissues of Lambs and Kids and Their in-between Relationship

by Zoi Skaperda, Ioannis D. Kyriazis, Fotios Tekos, Maria V. Alvanou, Paraskevi-Maria Nechalioti, Sotiria Makri, Angeliki Argyriadou, Sotiria Vouraki, Theodoros Kallitsis, Maria Kourti, Valasi Irene, Georgios Arsenos and Demetrios Kouretas

Antioxidants 2022, 11(10), 2065; https://doi.org/10.3390/antiox11102065 - 20 Oct 2022

Cited by 3 | Viewed by 1790

Abstract

The objective of this study was to assess the resting values of the physiological oxidative stress exhibited by lambs and kids reared in Greece, and the potential correlations between redox biomarker levels in blood and other tissues (liver, diaphragm, quadriceps, psoas major muscle). [...] Read more.

The objective of this study was to assess the resting values of the physiological oxidative stress exhibited by lambs and kids reared in Greece, and the potential correlations between redox biomarker levels in blood and other tissues (liver, diaphragm, quadriceps, psoas major muscle). For this purpose, lambs and kids at different developmental stages (d.s.) were used. The latter corresponded to four live weight categories (LWC), each representing 25%, 35%, 70% and 100% of mature body weight. In each of the above tissues, the levels of five common redox biomarkers were determined: glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), thiobarbituric reactive substances (TBARS), and protein carbonyls (CARBS). The results revealed that lambs and kids belonging to the 35% LWC had weaker endogenous antioxidant pools, while animals in the 70% and 100% LWC had elevated intrinsic antioxidant defense systems. Blood redox biomarkers were associated with the respective ones measured in the diaphragm, liver, quadriceps, and psoas major of both species. Importantly, TBARS levels in blood of animals in the 25% and 100% LWC are correlated with the TBARS levels in all other tissues tested. Blood antioxidant parameters might be used as potential biomarkers to predict the antioxidant status of tissues that affect meat quality. The latter would facilitate quality assessment prior to slaughter, allowing for timely nutritional interventions that can improve meat products. Full article

(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry)

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16 pages, 656 KiB

Open AccessReview

Role of Nutrients and Foods in Attenuation of Cardiac Remodeling through Oxidative Stress Pathways

by Taline Lazzarin, Leonardo Rufino Garcia, Danilo Martins, Diego Aparecido Rios Queiroz, Carolina Rodrigues Tonon, Paola da Silva Balin, Bertha Furlan Polegato, Sergio Alberto Rupp de Paiva, Paula Schmidt Azevedo, Marcos Minicucci and Leonardo Zornoff

Antioxidants 2022, 11(10), 2064; https://doi.org/10.3390/antiox11102064 - 20 Oct 2022

Cited by 7 | Viewed by 2051

Abstract

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that manifest clinically as changes in the heart’s size, mass, geometry, and function after different injuries. Importantly, remodeling is associated with increased risk of ventricular dysfunction and heart failure. Therefore, [...] Read more.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that manifest clinically as changes in the heart’s size, mass, geometry, and function after different injuries. Importantly, remodeling is associated with increased risk of ventricular dysfunction and heart failure. Therefore, strategies to attenuate this process are critical. Reactive oxygen species and oxidative stress play critical roles in remodeling. Importantly, antioxidative dietary compounds potentially have protective properties against remodeling. Therefore, this review evaluates the role of nutrients and food as modulators of cardiac remodeling. Full article

(This article belongs to the Special Issue Role of Oxidative Stress in Cardiac Remodeling and Heart Failure)

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22 pages, 6391 KiB

Open AccessArticle

Prevention of Testicular Damage by Indole Derivative MMINA via Upregulated StAR and CatSper Channels with Coincident Suppression of Oxidative Stress and Inflammation: In Silico and In Vivo Validation

by Tayyaba Afsar, Suhail Razak, Janeen H. Trembley, Khushbukhat Khan, Maria Shabbir, Ali Almajwal, Nawaf W. Alruwaili and Muhammad Umar Ijaz

Antioxidants 2022, 11(10), 2063; https://doi.org/10.3390/antiox11102063 - 19 Oct 2022

Cited by 6 | Viewed by 2511

Abstract

Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were [...] Read more.

Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were treated with saline, DMSO, CDDP, CDDP + MMINA, or MMINA. Reproductive hormones, antioxidant enzyme activity, histopathology, daily sperm production, and oxidative stress markers were examined. Western blot analysis was performed to access the expression of steroidogenic acute regulatory protein (StAR) and inflammatory biomarker expression in testis, while expression of calcium-dependent cation channel of sperm (CatSper) in epididymis was examined. The structural and dynamic molecular docking behavior of MMINA was analyzed using bioinformatics tools. The construction of molecular interactions was performed through KEGG, DAVID, and STRING databases. MMINA treatment reversed CDDP-induced nitric oxide (NO) and malondialdehyde (MDA) augmentation, while boosting the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the epididymis and testicular tissues. CDDP treatment significantly lowered sperm count, sperm motility, and epididymis sperm count. Furthermore, CDDP reduced epithelial height and tubular diameter and increased luminal diameter with impaired spermatogenesis. MMINA rescued testicular damage caused by CDDP. MMINA rescued CDDP-induced reproductive dysfunctions by upregulating the expression of the CatSper protein, which plays an essential role in sperm motility, MMINA increased testosterone secretion and StAR protein expression. MMINA downregulated the expression of NF-κB, STAT-3, COX-2, and TNF-α. Hydrogen bonding and hydrophobic interactions were predicted between MMINA and 3β-HSD, CatSper, NF-κβ, and TNFα. Molecular interactome outcomes depicted the formation of one hydrogen bond and one hydrophobic interaction between 3β-HSD that contributed to its strong binding with MMINA. CatSper also made one hydrophobic interaction and one hydrogen bond with MMINA but with a lower binding affinity of -7.7 relative to 3β-HSD, whereas MMINA made one hydrogen bond with NF-κβ residue Lys37 and TNF-α reside His91 and two hydrogen bonds with Lys244 and Thr456 of STAT3. Our experimental and in silico results revealed that MMINA boosted the antioxidant defense mechanism, restored the levels of fertility hormones, and suppressed histomorphological alterations. Full article

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13 pages, 1483 KiB

Open AccessArticle

Genetic Mechanism for Antioxidant Activity of Endogenous Enzymes under Salinity and Temperature Stress in Turbot (Scophthalmus maximus)

by Xinan Wang, Aijun Ma, Zhihui Huang, Zhibin Sun and Zhifeng Liu

Antioxidants 2022, 11(10), 2062; https://doi.org/10.3390/antiox11102062 - 19 Oct 2022

Viewed by 1740

Abstract

Three antioxidant properties (corresponding to the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase) were measured in the livers of Scophthalmus maximus under different salinities/temperatures (5, 10, 20, 30, and 40‰/17, 20, 23, 25, and 28 °C). Split-plot (SP) analysis, additive main effects, [...] Read more.

Three antioxidant properties (corresponding to the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase) were measured in the livers of Scophthalmus maximus under different salinities/temperatures (5, 10, 20, 30, and 40‰/17, 20, 23, 25, and 28 °C). Split-plot (SP) analysis, additive main effects, and multiplicative interaction (AMMI) and genotype × environment interaction (GGE) biplots were used to analyze genotype × salinity/temperature interactions for antioxidant properties. The results of the SP analysis show that the activity of the three antioxidant properties was significantly (p < 0.01) affected by salinity/temperature, antioxidant, and salinity/temperature × antioxidant interaction. The results of the AMMI analysis for salinity reveal that the effect of genotype, salinity, and genotype × salinity interaction on antioxidant properties reached a significant level (p < 0.001); 92.1065%, 2.6256%, and 4.4360% of the total sum of squares for antioxidant property activity were attributable to the effects of genotype, salinity, and genotype × salinity interaction, respectively. The results of GGE biplot analysis for salinity reveal differences in the activity ranking of the three antioxidant properties under five salinities; this difference expands with an decrease or increase in salinity from 30‰ (optimum salinity). A salinity of 5‰ had the strongest ability to identify the three antioxidant properties. The five experimental salinities were divided into one region, and SOD activity was the highest in this region. In a comprehensive analysis of stability and activity, SOD had the best activity and stability. The results of AMMI analysis for temperature reveal that genotype, temperature, and genotype × temperature interaction had significant effects on the antioxidant properties (p < 0.001); 82.4720%, 4.0666%, and 12.0968% of the total sum of squares for antioxidant property activity were attributable to the effects of genotype, temperature, and genotype × temperature interaction, respectively. The results of GGE biplot analysis for temperature reveal a large difference in the activity ranking of antioxidant properties between 17 °C and the other four temperatures, while only small differences in the activity rankings were detected among the other four temperatures. The difference in the activity ranking of antioxidant properties was greatest between the temperatures of 17 and 20 °C. A temperature of 17 °C showed the strongest ability to distinguish the three antioxidant properties. Additionally, the five test temperatures were grouped into one region, and comprehensive analysis of activity and stability showed that SOD had the best activity and stability. Full article

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12 pages, 1687 KiB

Open AccessReview

Redox Status Is the Mainstay of SARS-CoV-2 and Host for Producing Therapeutic Opportunities

by Anand Thirupathi, Yaodong Gu, Zsolt Radak and Ricardo A Pinho

Antioxidants 2022, 11(10), 2061; https://doi.org/10.3390/antiox11102061 - 19 Oct 2022

Cited by 2 | Viewed by 2495

Abstract

Over hundreds of years, humans have faced multiple pandemics and have overcome many of them with scientific advancements. However, the recent coronavirus disease (COVID-19) has challenged the physical, mental, and socioeconomic aspects of human life, which has introduced a general sense of uncertainty [...] Read more.

Over hundreds of years, humans have faced multiple pandemics and have overcome many of them with scientific advancements. However, the recent coronavirus disease (COVID-19) has challenged the physical, mental, and socioeconomic aspects of human life, which has introduced a general sense of uncertainty among everyone. Although several risk profiles, such as the severity of the disease, infection rate, and treatment strategy, have been investigated, new variants from different parts of the world put humans at risk and require multiple strategies simultaneously to control the spread. Understanding the entire system with respect to the commonly involved or essential mechanisms may be an effective strategy for successful treatment, particularly for COVID-19. Any treatment for COVID-19 may alter the redox profile, which can be an effective complementary method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and further replication. Indeed, redox profiles are one of the main barriers that suddenly shift the immune response in favor of COVID-19. Fortunately, several redox components exhibit antiviral and anti-inflammatory activities. However, access to these components as support elements against COVID-19 is limited. Therefore, understanding redox-derived species and their nodes as a common interactome in the system will facilitate the treatment of COVID-19. This review discusses the redox-based perspectives of the entire system during COVID-19 infection, including how redox-based molecules impact the accessibility of SARS-CoV-2 to the host and further replication. Additionally, to demonstrate its feasibility as a viable approach, we discuss the current challenges in redox-based treatment options for COVID-19. Full article

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17 pages, 6661 KiB

Open AccessArticle

Integrated Physiological, Transcriptomic, and Proteomic Analyses Reveal the Regulatory Role of Melatonin in Tomato Plants’ Response to Low Night Temperature

by Xiaolong Yang, Yumeng Zhang, Ting Liu, Jiali Shi, Mingfang Qi, Yufeng Liu and Tianlai Li

Antioxidants 2022, 11(10), 2060; https://doi.org/10.3390/antiox11102060 - 19 Oct 2022

Cited by 5 | Viewed by 2477

Abstract

Melatonin is a direct free radical scavenger that has been demonstrated to increase plants’ resistance to a variety of stressors. Here, we sought to examine the effect of melatonin on tomato seedlings subjected to low night temperatures using an integrated physiological, transcriptomic, and [...] Read more.

Melatonin is a direct free radical scavenger that has been demonstrated to increase plants’ resistance to a variety of stressors. Here, we sought to examine the effect of melatonin on tomato seedlings subjected to low night temperatures using an integrated physiological, transcriptomic, and proteomic approach. We found that a pretreatment with 100 μM melatonin increased photosynthetic and transpiration rates, stomatal apertures, and peroxidase activity, and reduced chloroplast damage of the tomato plant under a low night temperature. The melatonin pretreatment reduced the photoinhibition of photosystem I by regulating the balance of both donor- and acceptor-side restriction of PSI and by increasing electron transport. Furthermore, the melatonin pretreatment improved the photosynthetic performance of proton gradient regulation 5 (SlPGR5) and SlPGR5-like photosynthetic phenotype 1 (SlPGRL1)-suppressed transformants under a low night temperature stress. Transcriptomic and proteomic analyses found that the melatonin pretreatment resulted in the upregulation of genes and proteins related to transcription factors, signal transduction, environmental adaptation, and chloroplast integrity maintenance in low night temperature-stressed tomato plants. Collectively, our results suggest that melatonin can effectively improve the photosynthetic efficiency of tomato plants under a low night temperature and provide novel insights into the molecular mechanism of melatonin-mediated abiotic stress resistance. Full article

(This article belongs to the Special Issue Antioxidant Mechanisms in Plants)

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15 pages, 2911 KiB

Open AccessArticle

Sustainable Dyeing and Functionalization of Different Fibers Using Orange Peel Extract’s Antioxidants

by Aleksandra Ivanovska, Ivana Savić Gajić, Jelena Lađarević, Marija Milošević, Ivan Savić, Katarina Mihajlovski and Mirjana Kostić

Antioxidants 2022, 11(10), 2059; https://doi.org/10.3390/antiox11102059 - 19 Oct 2022

Cited by 7 | Viewed by 2695

Abstract

A diluted ethanol orange peel extract was used for sustainable dyeing and functionalization of different fabrics. The extract analysis was performed using UPLC-ESI-MS/MS; its total flavonoid (0.67 g RE/100 g d.w.) and antioxidant (2.81 g GAE/100 g d.w.) contents and antioxidant activity (IC [...] Read more.

A diluted ethanol orange peel extract was used for sustainable dyeing and functionalization of different fabrics. The extract analysis was performed using UPLC-ESI-MS/MS; its total flavonoid (0.67 g RE/100 g d.w.) and antioxidant (2.81 g GAE/100 g d.w.) contents and antioxidant activity (IC₅₀ of 65.5 µg/mL) were also determined. The extract dyeing performance at various dyebath pH values was evaluated using multifiber fabric. Among six fabrics, extract possessed the ability for dyeing wool, polyamide, and cellulose acetate (at pH 4.5), which color strength (K/S) values increased after washing (9.7–19.8 vs. 11.6–23.2). Extract:water ratio of 20:35 (v/v) was found to be sufficient for achieving satisfactory K/S values (i.e., 20.17, 12.56, and 10.38 for wool, polyamide, and cellulose acetate, respectively) that were slightly changed after washing. The optimal dyeing temperatures for wool, polyamide, and cellulose acetate are 55, 35, and 25 °C, while the equilibrium dye exhaustion at those temperatures was achieved after 45, 120, and 90 min, respectively. The color coordinate measurements revealed that wool and polyamide fabrics are yellower than cellulose acetate, while, compared to polyamide and cellulose acetate, wool is redder. Possible interactions between selected fabrics and extract compounds are suggested. All fabrics possessed excellent antioxidant activity (88.6–99.6%) both before and after washing. Cellulose acetate provided maximum bacterial reduction (99.99%) for Escherichia coli, and Staphylococcus aureus, which in the case of Staphylococcus aureus remained unchanged after washing. Orange peel extract could be used for simultaneous dyeing and functionalization of wool and polyamide (excellent antioxidant activity) and cellulose acetate (excellent antioxidant and antibacterial activity) fabrics. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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18 pages, 4642 KiB

Open AccessArticle

Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study

by Ali Khattib, Sanaa Musa, Majdi Halabi, Tony Hayek and Soliman Khatib

Antioxidants 2022, 11(10), 2058; https://doi.org/10.3390/antiox11102058 - 19 Oct 2022

Cited by 6 | Viewed by 2271

Abstract

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active [...] Read more.

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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14 pages, 3026 KiB

Open AccessArticle

Fermented Ginger Extract in Natural Deep Eutectic Solvent Enhances Cytotoxicity by Inhibiting NF-κB Mediated CXC Chemokine Receptor 4 Expression in Oxaliplatin-Resistant Human Colorectal Cancer Cells

by Ko-Chao Lee, Kuen-Lin Wu, Shun-Fu Chang, Hsin-I Chang, Cheng-Nan Chen and Yih-Yuan Chen

Antioxidants 2022, 11(10), 2057; https://doi.org/10.3390/antiox11102057 - 19 Oct 2022

Cited by 9 | Viewed by 2436

Abstract

Ginger extracts have been shown to have health-promoting pharmacological activity and beneficial effects, including antioxidant and anticancer properties. The extraction of ginger by natural deep eutectic solvents (NaDES) has been shown to enhance bioactivity, but the cytotoxicity of NaDES extracts needs to be [...] Read more.

Ginger extracts have been shown to have health-promoting pharmacological activity and beneficial effects, including antioxidant and anticancer properties. The extraction of ginger by natural deep eutectic solvents (NaDES) has been shown to enhance bioactivity, but the cytotoxicity of NaDES extracts needs to be further determined. Signaling through the CXC chemokine receptor 4 (CXCR4) expressed on colorectal cancer (CRC) cells has a pivotal role in tumor cell chemosensitivity. Oxaliplatin is a third-generation platinum compound used as an effective chemotherapeutic drug for CRC treatment. However, whether ginger extract and oxaliplatin could induce a synergistic cytotoxic effect in oxaliplatin-resistant CRC cells through modulating CXCR4 expression is not known. In this study, oxaliplatin-resistant HCT-116 (HCT-116/R) cells were generated first. Ginger was extracted using the NaDES mixture betaine/lactate/water (1:2:2.5). Lactobacillus reuteri fermentation of NaDES-ginger extract increased the total polyphenol content (12.42 mg gallic acid/g in non-fermented NaDES-ginger extract and 23.66 mg gallic acid/g in fermented NaDES-ginger extract). It also increased the antioxidant activity by about 20–30% compared to non-fermented NaDES-ginger extract. In addition, it achieved low cytotoxicity to normal colonic mucosal cells and enhanced the anticancer effect on HCT-116/R cells. On the other hand, the inhibition of NF-κB activation by fermented NaDES-ginger extract significantly decreased the CXCR4 expression (p < 0.05) in HCT-116/R cells. The inactivation of NF-κB by pharmacological inhibitor pyrrolidine dithiocarbamate further enhanced the fermented NaDES-ginger extract-reduced CXCR4 expression levels (p < 0.05). Moreover, fermented NaDES-ginger extract could synergistically increase the cytotoxicity of oxaliplatin by inhibiting CXCR4 expression and inactivating NF-κB, resulting in HCT-116/R cell death. These findings demonstrate that fermented NaDES-ginger extract reduces the NF-kB-mediated activation of CXCR4 and enhances oxaliplatin-induced cytotoxicity in oxaliplatin-resistant CRC cells. Full article

(This article belongs to the Special Issue Oxidative Stress Damage and Antioxidant Natural Products in Colorectal Diseases)

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15 pages, 2386 KiB

Open AccessArticle

A Chlorophyll-Derived Phylloxanthobilin Is a Potent Antioxidant That Modulates Immunometabolism in Human PBMC

by Cornelia A. Karg, Lucia Parráková, Dietmar Fuchs, Harald Schennach, Bernhard Kräutler, Simone Moser and Johanna M. Gostner

Antioxidants 2022, 11(10), 2056; https://doi.org/10.3390/antiox11102056 - 19 Oct 2022

Cited by 5 | Viewed by 2499

Abstract

Phyllobilins are natural products derived from the degradation of chlorophyll, which proceeds via a common and strictly controlled pathway in higher plants. The resulting tetrapyrrolic catabolites—the phyllobilins—are ubiquitous in nature; despite their high abundance, there is still a lack of knowledge about their [...] Read more.

Phyllobilins are natural products derived from the degradation of chlorophyll, which proceeds via a common and strictly controlled pathway in higher plants. The resulting tetrapyrrolic catabolites—the phyllobilins—are ubiquitous in nature; despite their high abundance, there is still a lack of knowledge about their physiological properties. Phyllobilins are part of human nutrition and were shown to be potent antioxidants accounting with interesting physiological properties. Three different naturally occurring types of phyllobilins—a phylloleucobilin, a dioxobilin-type phylloleucobilin and a phylloxanthobilin (PxB)—were compared regarding potential antioxidative properties in a cell-free and in a cell-based antioxidant activity test system, demonstrating the strongest effect for the PxB. Moreover, the PxB was investigated for its capacity to interfere with immunoregulatory metabolic pathways of tryptophan breakdown in human blood peripheral mononuclear cells. A dose-dependent inhibition of tryptophan catabolism to kynurenine was observed, suggesting a suppressive effect on pathways of cellular immune activation. Although the exact mechanisms of immunomodulatory effects are yet unknown, these prominent bioactivities point towards health-relevant effects, which warrant further mechanistic investigations and the assessment of the in vivo extrapolatability of results. Thus, phyllobilins are a still surprisingly unexplored family of natural products that merit further investigation. Full article

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13 pages, 2411 KiB

Open AccessArticle

Intracellular Polyphenol Wine Metabolites Oppose Oxidative Stress and Upregulate Nrf2/ARE Pathway

by Chiara Stranieri, Flavia Guzzo, Sofia Gambini, Luciano Cominacini and Anna Maria Fratta Pasini

Antioxidants 2022, 11(10), 2055; https://doi.org/10.3390/antiox11102055 - 19 Oct 2022

Cited by 7 | Viewed by 2237

Abstract

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant [...] Read more.

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant balance toward an antioxidant pattern of THP-1 cells and human cardiomyocytes through a gene regulatory system. First, we identified which metabolite polyphenols present in red wine extract cross cell membranes and may be responsible for antioxidant effects. The results showed that the wine metabolites in treated cells belonged mainly to stilbenes, flavan-3-ols derivatives, and flavonoids. Other metabolites present in cells were not typical wine metabolites. Then, we found that red wine extract dose-dependently lowered reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBHP) up to 50 ± 7% in both cell lines (p < 0.01). Furthermore, wine extract increased nuclear Nrf2 of about 35 ± 5% in both cell lines (p < 0.01) and counteracted its reduction induced by TBHP (p < 0.01). The rise in Nrf2 was paralleled by the increase in hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit gene expression (both mRNA and protein) (p < 0.01). These results could help explain the healthful activity of wine polyphenols within cells. Full article

(This article belongs to the Special Issue Potential Benefits of Antioxidant Phytochemicals on Endogenous Antioxidants Defences in Chronic Diseases)

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11 pages, 1299 KiB

Open AccessReview

Regulation of Retroviral and SARS-CoV-2 Protease Dimerization and Activity through Reversible Oxidation

by David A. Davis, Haydar Bulut, Prabha Shrestha, Hiroaki Mitsuya and Robert Yarchoan

Antioxidants 2022, 11(10), 2054; https://doi.org/10.3390/antiox11102054 - 18 Oct 2022

Cited by 2 | Viewed by 2064

Abstract

Most viruses encode their own proteases to carry out viral maturation and these often require dimerization for activity. Studies on human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2) and human T-cell leukemia virus (HTLV-1) proteases have shown that the activity of these [...] Read more.

Most viruses encode their own proteases to carry out viral maturation and these often require dimerization for activity. Studies on human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2) and human T-cell leukemia virus (HTLV-1) proteases have shown that the activity of these proteases can be reversibly regulated by cysteine (Cys) glutathionylation and/or methionine oxidation (for HIV-2). These modifications lead to inhibition of protease dimerization and therefore loss of activity. These changes are reversible with the cellular enzymes, glutaredoxin or methionine sulfoxide reductase. Perhaps more importantly, as a result, the maturation of retroviral particles can also be regulated through reversible oxidation and this has been demonstrated for HIV-1, HIV-2, Mason-Pfizer monkey virus (M-PMV) and murine leukemia virus (MLV). More recently, our group has learned that SARS-CoV-2 main protease (M^pro) dimerization and activity can also be regulated through reversible glutathionylation of Cys300. Overall, these studies reveal a conserved way for viruses to regulate viral polyprotein processing particularly during oxidative stress and reveal novel targets for the development of inhibitors of dimerization and activity of these important viral enzyme targets. Full article

(This article belongs to the Special Issue Glutaredoxin and Glutathione)

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19 pages, 2193 KiB

Open AccessArticle

Transposon-Directed Insertion-Site Sequencing Reveals Glycolysis Gene gpmA as Part of the H₂O₂ Defense Mechanisms in Escherichia coli

by Myriam Roth, Emily C. A. Goodall, Karthik Pullela, Vincent Jaquet, Patrice François, Ian R. Henderson and Karl-Heinz Krause

Antioxidants 2022, 11(10), 2053; https://doi.org/10.3390/antiox11102053 - 18 Oct 2022

Cited by 5 | Viewed by 2503

Abstract

Hydrogen peroxide (H₂O₂) is a common effector of defense mechanisms against pathogenic infections. However, bacterial factors involved in H₂O₂ tolerance remain unclear. Here we used transposon-directed insertion-site sequencing (TraDIS), a technique allowing the screening of the [...] Read more.

Hydrogen peroxide (H₂O₂) is a common effector of defense mechanisms against pathogenic infections. However, bacterial factors involved in H₂O₂ tolerance remain unclear. Here we used transposon-directed insertion-site sequencing (TraDIS), a technique allowing the screening of the whole genome, to identify genes implicated in H₂O₂ tolerance in Escherichia coli. Our TraDIS analysis identified 10 mutants with fitness defect upon H₂O₂ exposure, among which previously H₂O₂-associated genes (oxyR, dps, dksA, rpoS, hfq and polA) and other genes with no known association with H₂O₂ tolerance in E. coli (corA, rbsR, nhaA and gpmA). This is the first description of the impact of gpmA, a gene involved in glycolysis, on the susceptibility of E. coli to H₂O₂. Indeed, confirmatory experiments showed that the deletion of gpmA led to a specific hypersensitivity to H₂O₂ comparable to the deletion of the major H₂O₂ scavenger gene katG. This hypersensitivity was not due to an alteration of catalase function and was independent of the carbon source or the presence of oxygen. Transcription of gpmA was upregulated under H₂O₂ exposure, highlighting its role under oxidative stress. In summary, our TraDIS approach identified gpmA as a member of the oxidative stress defense mechanism in E. coli. Full article

(This article belongs to the Special Issue A Lesson from Microorganisms: How to Counteract Oxidative Stress)

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15 pages, 2354 KiB

Open AccessArticle

Fermented and Aged Ginseng Sprouts (Panax ginseng) and Their Main Component, Compound K, Alleviate Asthma Parameters in a Mouse Model of Allergic Asthma through Suppression of Inflammation, Apoptosis, ER Stress, and Ferroptosis

by Ji Hyeon Ryu, Min Seok Woo, Dang Long Cao, Eun-Jin Kim, Yi Yeong Jeong, Eun-Ha Koh, Kye Man Cho, Sang Soo Kang and Dawon Kang

Antioxidants 2022, 11(10), 2052; https://doi.org/10.3390/antiox11102052 - 18 Oct 2022

Cited by 16 | Viewed by 3513

Abstract

The association between asthma and oxidative stress remains controversial. Oxidative stress-induced ferroptosis has not been extensively studied in asthma models. This study was performed to investigate the anti-asthmatic and anti-ferroptotic effects of fermented and aged ginseng sprouts (FAGS) with enhanced antioxidant activity and [...] Read more.

The association between asthma and oxidative stress remains controversial. Oxidative stress-induced ferroptosis has not been extensively studied in asthma models. This study was performed to investigate the anti-asthmatic and anti-ferroptotic effects of fermented and aged ginseng sprouts (FAGS) with enhanced antioxidant activity and its main component, compound K (CK), in a mouse model of ovalbumin (OVA)-induced allergic asthma. The experimental asthma model was sensitized and challenged with OVA. During the challenge period, two different concentrations of FAGS and CK were administered via oral gavage. Asthmatic parameters were analyzed in bronchoalveolar lavage fluid (BALF), blood, and lung tissue. CK, among the ginsenosides analyzed, was highly increased in FAGS compared with GS. Asthma parameters, such as Th2 cytokine and IgE production, mast cell activation, goblet cell hyperplasia, hyperresponsiveness, and inflammation, were dramatically increased in the OVA group. Oxidation and ferroptosis markers were increased in the OVA group. The asthma parameters and ferroptosis markers were markedly decreased in the OVA + FAGS and OVA + CK groups. These results showed that FAGS and CK alleviated asthma parameters in an allergic asthma mouse model by inhibiting inflammation and ferroptosis. Our findings suggest that FAGS and CK could be used as potential treatments for allergic asthma. Full article

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Antioxidants, Volume 11, Issue 10 (October 2022) – 236 articles

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