Antioxidants

9 pages, 1027 KiB

Open AccessOpinion

Selenoprotein: Potential Player in Redox Regulation in Chlamydomonas reinhardtii

by Sandip A. Ghuge, Ulhas Sopanrao Kadam and Jong Chan Hong

Antioxidants 2022, 11(8), 1630; https://doi.org/10.3390/antiox11081630 - 22 Aug 2022

Cited by 8 | Viewed by 2441

Selenium (Se) is an essential micro-element for many organisms, including Chlamydomonas reinhardtii, and is required in trace amounts. It is obtained from the 21st amino acid selenocysteine (Sec, U), genetically encoded by the UGA codon. Proteins containing Sec are known as selenoproteins. [...] Read more.

Selenium (Se) is an essential micro-element for many organisms, including Chlamydomonas reinhardtii, and is required in trace amounts. It is obtained from the 21st amino acid selenocysteine (Sec, U), genetically encoded by the UGA codon. Proteins containing Sec are known as selenoproteins. In eukaryotes, selenoproteins are present in animals and algae, whereas fungi and higher plants lack them. The human genome contains 25 selenoproteins, most of which are involved in antioxidant defense activity, redox regulation, and redox signaling. In algae, 42 selenoprotein families were identified using various bioinformatics approaches, out of which C. reinhardtii is known to have 10 selenoprotein genes. However, the role of selenoproteins in Chlamydomonas is yet to be reported. Chlamydomonas selenoproteins contain conserved domains such as CVNVGC and GCUG, in the case of thioredoxin reductase, and CXXU in other selenoproteins. Interestingly, Sec amino acid residue is present in a catalytically active domain in Chlamydomonas selenoproteins, similar to human selenoproteins. Based on catalytical active sites and conserved domains present in Chlamydomonas selenoproteins, we suggest that Chlamydomonas selenoproteins could have a role in redox regulation and defense by acting as antioxidants in various physiological conditions. Full article

(This article belongs to the Special Issue Antioxidants in Algae: Extraction, Components, and Applications)

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22 pages, 2616 KiB

Open AccessArticle

Red Palm Oil Ameliorates Oxidative Challenge and Inflammatory Responses Associated with Lipopolysaccharide-Induced Hepatic Injury by Modulating NF-κβ and Nrf2/GCL/HO-1 Signaling Pathways in Rats

by Olawale R. Ajuwon, Jeanine L. Marnewick, Oluwafemi O. Oguntibeju and Lester M. Davids

Antioxidants 2022, 11(8), 1629; https://doi.org/10.3390/antiox11081629 - 22 Aug 2022

Cited by 9 | Viewed by 3848

Abstract

Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant [...] Read more.

Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant and anti-inflammatory effects. In this study, we assess the protective effect and mechanistic action of RPO using a lipopolysaccharide (LPS)-induced hepatic injury model. Male Wistar rats were assigned into four groups (10 animals/group): normal control (NC), RPO, LPS and RPO + LPS. Animals in the RPO and RPO + LPS groups were administered RPO (200 μL/day) for 28 days. On the 27th day of experiment, animals in LPS and RPO + LPS groups were injected with LPS (0.5 mg/kg body weight). Animals were sacrificed 24 h later, and blood and liver tissues harvested for biochemical and molecular analysis. RPO resolved hepatic histological dysfunction induced by LPS, and lowered alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transferase activities in the serum. Hepatic malondialdehyde and conjugated dienes, as well as pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6 and TNFα were significantly diminished (p < 0.05) by RPO pre-treatment. Activity of hepatic antioxidant enzymes including superoxide dismutase, glutathione reductase, glutathione peroxidase, as well as glutathione redox status (GSH:GSSG), and markers of antioxidant capacity that decreased as a result of LPS injection were improved by RPO pre-treatment. Mechanistically, RPO up-regulated mRNA expression of redox sensitive transcription factor Nrf2 and its downstream targets GCL and HO-1, while also suppressing the expression of NFκβ and associated inflammatory protein, Iκβ kinase (IκKβ). In conclusion, this study highlights the ameliorating effects of RPO against LPS-induced hepatic injury and revealed the Nrf2/GCL/HO-1 and NFκβ signaling axis as potential contributing mechanisms. Full article

(This article belongs to the Special Issue Efficacy of Dietary Molecules in the Modulation of Redox Homeostasis of Rodent Models)

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15 pages, 3469 KiB

Open AccessArticle

Melatonin Decreases Acute Inflammatory Response to Neural Probe Insertion

by Daniela D. Krahe, Kevin M. Woeppel, Qianru Yang, Neetu Kushwah and Xinyan Tracy Cui

Antioxidants 2022, 11(8), 1628; https://doi.org/10.3390/antiox11081628 - 22 Aug 2022

Cited by 4 | Viewed by 2671

Abstract

Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the [...] Read more.

Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress in the tissue surrounding implanted probes in C57BL/6 mice as well as two-photon microscopy to track the microglial responses to the probes in real-time in transgenic mice expressing GFP with CX3CR1 promotor. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia and astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglial encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces. Full article

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18 pages, 2158 KiB

Open AccessArticle

Uptake and Immunomodulatory Properties of Betanin, Vulgaxanthin I and Indicaxanthin towards Caco-2 Intestinal Cells

by Yunqing Wang, Ganwarige Sumali N. Fernando, Natalia N. Sergeeva, Nikolaos Vagkidis, Victor Chechik, Thuy Do, Lisa J. Marshall and Christine Boesch

Antioxidants 2022, 11(8), 1627; https://doi.org/10.3390/antiox11081627 - 22 Aug 2022

Cited by 13 | Viewed by 2854

Abstract

The present study aimed to compare the absorption and transport patterns of three main betalains, betanin, vulgaxanthin I and indicaxanthin, into intestinal epithelial cells and to assess their distinct molecular effects on inflammatory and redox-related cell signalling in association with their radial scavenging [...] Read more.

The present study aimed to compare the absorption and transport patterns of three main betalains, betanin, vulgaxanthin I and indicaxanthin, into intestinal epithelial cells and to assess their distinct molecular effects on inflammatory and redox-related cell signalling in association with their radial scavenging potencies. All three betalains showed anti-inflammatory effects (5–80 μM), reflected by attenuated transcription of pro-inflammatory mediators such as cyclooxygenase-2 and inducible NO-synthase. Concomitant increases in antioxidant enzymes such as heme oxygenase-1 were only observed for betanin. Moreover, betanin uniquely demonstrated a potent dose-dependent radical scavenging activity in EPR and cell-based assays. Results also indicated overall low permeability for the three betalains with P_app of 4.2–8.9 × 10⁻⁷ cm s⁻¹. Higher absorption intensities of vulgaxanthin and indicaxanthin may be attributed to smaller molecular sizes and greater lipophilicity. In conclusion, betanin, vulgaxanthin I and indicaxanthin have differentially contributed to lowering inflammatory markers and mitigating oxidative stress, implying the potential to ameliorate inflammatory intestinal disease. Compared with two betaxanthins, the greater efficacy of betanin in scavenging radical and promoting antioxidant response might, to some extent, compensate for its poorer absorption efficiency, as demonstrated by the Caco-2 cell model. Full article

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26 pages, 7104 KiB

Open AccessArticle

Whole-Genome Identification of APX and CAT Gene Families in Cultivated and Wild Soybeans and Their Regulatory Function in Plant Development and Stress Response

by Muqadas Aleem, Saba Aleem, Iram Sharif, Maida Aleem, Rahil Shahzad, Muhammad Imran Khan, Amina Batool, Gulam Sarwar, Jehanzeb Farooq, Azeem Iqbal, Basit Latief Jan, Prashant Kaushik, Xianzhong Feng, Javaid Akhter Bhat and Parvaiz Ahmad

Antioxidants 2022, 11(8), 1626; https://doi.org/10.3390/antiox11081626 - 22 Aug 2022

Cited by 14 | Viewed by 3412

Abstract

Plants coevolved with their antioxidant defense systems, which detoxify and adjust levels of reactive oxygen species (ROS) under multiple plant stresses. We performed whole-genome identification of ascorbate peroxidase (APX) and catalase (CAT) families in cultivated and wild soybeans. In cultivated and wild soybean [...] Read more.

Plants coevolved with their antioxidant defense systems, which detoxify and adjust levels of reactive oxygen species (ROS) under multiple plant stresses. We performed whole-genome identification of ascorbate peroxidase (APX) and catalase (CAT) families in cultivated and wild soybeans. In cultivated and wild soybean genomes, we identified 11 and 10 APX genes, respectively, whereas the numbers of identified CAT genes were four in each species. Comparative phylogenetic analysis revealed more homology among cultivated and wild soybeans relative to other legumes. Exon/intron structure, motif and synteny blocks are conserved in cultivated and wild species. According to the Ka/Ks value, purifying selection is a major force for evolution of these gene families in wild soybean; however, the APX gene family was evolved by both positive and purifying selection in cultivated soybean. Segmental duplication was a major factor involved in the expansion of APX and CAT genes. Expression patterns revealed that APX and CAT genes are differentially expressed across fourteen different soybean tissues under water deficit (WD), heat stress (HS) and combined drought plus heat stress (WD + HS). Altogether, the current study provides broad insights into these gene families in soybeans. Our results indicate that APX and CAT gene families modulate multiple stress response in soybeans. Full article

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

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21 pages, 3494 KiB

Open AccessArticle

Antioxidant Therapy Significantly Attenuates Hepatotoxicity following Low Dose Exposure to Microcystin-LR in a Murine Model of Diet-Induced Non-Alcoholic Fatty Liver Disease

by Apurva Lad, Jonathan Hunyadi, Jacob Connolly, Joshua D. Breidenbach, Fatimah K. Khalaf, Prabhatchandra Dube, Shungang Zhang, Andrew L. Kleinhenz, David Baliu-Rodriguez, Dragan Isailovic, Terry D. Hinds, Jr., Cara Gatto-Weis, Lauren M. Stanoszek, Thomas M. Blomquist, Deepak Malhotra, Steven T. Haller and David J. Kennedy

Antioxidants 2022, 11(8), 1625; https://doi.org/10.3390/antiox11081625 - 22 Aug 2022

Cited by 9 | Viewed by 2724

Abstract

We have previously shown in a murine model of Non-alcoholic Fatty Liver Disease (NAFLD) that chronic, low-dose exposure to the Harmful Algal Bloom cyanotoxin microcystin-LR (MC-LR), resulted in significant hepatotoxicity including micro-vesicular lipid accumulation, impaired toxin metabolism as well as dysregulation of the [...] Read more.

We have previously shown in a murine model of Non-alcoholic Fatty Liver Disease (NAFLD) that chronic, low-dose exposure to the Harmful Algal Bloom cyanotoxin microcystin-LR (MC-LR), resulted in significant hepatotoxicity including micro-vesicular lipid accumulation, impaired toxin metabolism as well as dysregulation of the key signaling pathways involved in inflammation, immune response and oxidative stress. On this background we hypothesized that augmentation of hepatic drug metabolism pathways with targeted antioxidant therapies would improve MC-LR metabolism and reduce hepatic injury in NAFLD mice exposed to MC-LR. We chose N-acetylcysteine (NAC, 40 mM), a known antioxidant that augments the glutathione detoxification pathway and a novel peptide (pNaKtide, 25 mg/kg) which is targeted to interrupting a specific Src-kinase mediated pro-oxidant amplification mechanism. Histological analysis showed significant increase in hepatic inflammation in NAFLD mice exposed to MC-LR which was attenuated on treatment with both NAC and pNaKtide (both p ≤ 0.05). Oxidative stress, as measured by 8-OHDG levels in urine and protein carbonylation in liver sections, was also significantly downregulated upon treatment with both antioxidants after MC-LR exposure. Genetic analysis of key drug transporters including Abcb1a, Phase I enzyme-Cyp3a11 and Phase II metabolic enzymes-Pkm (Pyruvate kinase, muscle), Pklr (Pyruvate kinase, liver, and red blood cell) and Gad1 (Glutamic acid decarboxylase) was significantly altered by MC-LR exposure as compared to the non-exposed control group (all p ≤ 0.05). These changes were significantly attenuated with both pNaKtide and NAC treatment. These results suggest that MC-LR metabolism and detoxification is significantly impaired in the setting of NAFLD, and that these pathways can potentially be reversed with targeted antioxidant treatment. Full article

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18 pages, 1861 KiB

Open AccessReview

Plant Glutathione Peroxidases: Non-Heme Peroxidases with Large Functional Flexibility as a Core Component of ROS-Processing Mechanisms and Signalling

by Krisztina Bela, Riyazuddin Riyazuddin and Jolán Csiszár

Antioxidants 2022, 11(8), 1624; https://doi.org/10.3390/antiox11081624 - 21 Aug 2022

Cited by 28 | Viewed by 4351

Abstract

Glutathione peroxidases (GPXs) are non-heme peroxidases catalyzing the reduction of H₂O₂ or organic hydroperoxides to water or corresponding alcohols using glutathione (GSH) or thioredoxin (TRX) as a reducing agent. In contrast to animal GPXs, the plant enzymes are non-seleno monomeric [...] Read more.

Glutathione peroxidases (GPXs) are non-heme peroxidases catalyzing the reduction of H₂O₂ or organic hydroperoxides to water or corresponding alcohols using glutathione (GSH) or thioredoxin (TRX) as a reducing agent. In contrast to animal GPXs, the plant enzymes are non-seleno monomeric proteins that generally utilize TRX more effectively than GSH but can be a putative link between the two main redox systems. Because of the substantial differences compared to non-plant GPXs, use of the GPX-like (GPXL) name was suggested for Arabidopsis enzymes. GPX(L)s not only can protect cells from stress-induced oxidative damages but are crucial components of plant development and growth. Due to fine-tuning the H₂O₂ metabolism and redox homeostasis, they are involved in the whole life cycle even under normal growth conditions. Significantly new mechanisms were discovered related to their transcriptional, post-transcriptional and post-translational modifications by describing gene regulatory networks, interacting microRNA families, or identifying Lys decrotonylation in enzyme activation. Their involvement in epigenetic mechanisms was evidenced. Detailed genetic, evolutionary, and bio-chemical characterization, and comparison of the main functions of GPXs, demonstrated their species-specific roles. The multisided involvement of GPX(L)s in the regulation of the entire plant life ensure that their significance will be more widely recognized and applied in the future. Full article

(This article belongs to the Special Issue The Role of Peroxidases and Catalases in Photosynthetic and Non–photosynthetic Eukaryotes)

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30 pages, 9345 KiB

Open AccessArticle

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

by Shabnam Shabir, Sumaira Yousuf, Sandeep Kumar Singh, Emanuel Vamanu and Mahendra P. Singh

Antioxidants 2022, 11(8), 1623; https://doi.org/10.3390/antiox11081623 - 21 Aug 2022

Cited by 20 | Viewed by 3831

Abstract

Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. [...] Read more.

Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. This study aimed to compare the ethnopharmacological effects of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) on the amelioration of rotenone-induced toxicity in wild-type Drosophila melanogaster (Oregon R⁺) at biochemical, cellular, and behavioral levels. Phytoextracts were prepared from all three plants, i.e., UD, MC, and MK (aqueous and ethanolic fractions), and their bioactive compounds were evaluated using in vitro biochemical parameters (DPPH, ABTS, TPC, and TFC), UV-Vis, followed by FT-IR and HPLC. Third instar larvae and freshly eclosed flies were treated with 500 µM rotenone alone or in combination with UD, MC, and MK for 24 to 120 h. Following exposure, cytotoxicity (dye exclusion test), biochemical (protein estimation and acetylcholinesterase inhibition assays), and behavioral assays (climbing and jumping assays) were performed. Among all three plant extracts, MK exhibited the highest antioxidant properties due to the highest TPC, TFC, DPPH, and ABTS, followed by UD, then MC. The overall trend was MK > UD > MC. In this context, ethnopharmacological properties mimic the same effect in Drosophila, exhibiting significantly (p < 0.05) reduced cytotoxicity (trypan blue), improved biochemical parameters (proteotoxicity and AChE activity), and better behavioral parameters in the organisms cotreated with phyto extracts compared with rotenone. Conclusively, UV-Vis, FTIR, and HPLC analyses differentiated the plant extracts. The findings of this research may be beneficial in the use of select herbs as viable sources of phyto-ingredients that could be of interest in nutraceutical development and various clinical applications. Full article

(This article belongs to the Special Issue Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants)

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22 pages, 2185 KiB

Open AccessArticle

Analysis of Thioredoxins and Glutaredoxins in Soybean: Evidence of Translational Regulation under Water Restriction

by María Martha Sainz, Carla Valeria Filippi, Guillermo Eastman, José Sotelo-Silveira, Omar Borsani and Mariana Sotelo-Silveira

Antioxidants 2022, 11(8), 1622; https://doi.org/10.3390/antiox11081622 - 21 Aug 2022

Cited by 9 | Viewed by 2336 | Correction

Abstract

Soybean (Glycine max (L.) Merr.) establishes symbiosis with rhizobacteria, developing the symbiotic nodule, where the biological nitrogen fixation (BNF) occurs. The redox control is key for guaranteeing the establishment and correct function of the BNF process. Plants have many antioxidative systems involved [...] Read more.

Soybean (Glycine max (L.) Merr.) establishes symbiosis with rhizobacteria, developing the symbiotic nodule, where the biological nitrogen fixation (BNF) occurs. The redox control is key for guaranteeing the establishment and correct function of the BNF process. Plants have many antioxidative systems involved in ROS homeostasis and signaling, among them a network of thio- and glutaredoxins. Our group is particularly interested in studying the differential response of nodulated soybean plants to water-deficit stress. To shed light on this phenomenon, we set up an RNA-seq experiment (for total and polysome-associated mRNAs) with soybean roots comprising combined treatments including the hydric and the nodulation condition. Moreover, we performed the initial identification and description of the complete repertoire of thioredoxins (Trx) and glutaredoxins (Grx) in soybean. We found that water deficit altered the expression of a greater number of differentially expressed genes (DEGs) than the condition of plant nodulation. Among them, we identified 12 thioredoxin (Trx) and 12 glutaredoxin (Grx) DEGs, which represented a significant fraction of the detected GmTrx and GmGrx in our RNA-seq data. Moreover, we identified an enriched network in which a GmTrx and a GmGrx interacted with each other and associated through several types of interactions with nitrogen metabolism enzymes. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems II)

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13 pages, 1219 KiB

Open AccessReview

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

by Javier Florido, César Rodriguez-Santana, Laura Martinez-Ruiz, Alba López-Rodríguez, Darío Acuña-Castroviejo, Iryna Rusanova and Germaine Escames

Antioxidants 2022, 11(8), 1621; https://doi.org/10.3390/antiox11081621 - 20 Aug 2022

Cited by 30 | Viewed by 7191

Abstract

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by [...] Read more.

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by ROS levels and by decreasing the capacity of the antioxidant system, leading to programmed cell death. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. Despite being widely recognized as a pro-oxidant molecule in tumor cells, the mechanism of action of melatonin remains unclear, which has hindered its use in clinical treatments. The current review aims to describe and clarify the proposed mechanism of action of melatonin inducing ROS production in cancer cells in order to propose future anti-neoplastic clinical applications. Full article

(This article belongs to the Special Issue Free-Radical Scavenging and Antioxidant Properties of Melatonin)

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12 pages, 2439 KiB

Open AccessArticle

Glibenclamide Increases Nitric Oxide Levels and Decreases Oxidative Stress in an In Vitro Model of Preeclampsia

by Priscila Rezeck Nunes, Thaina Omia Bueno Pereira, Mariana Bertozzi Matheus, Nubia Alves Grandini, Juliana Silva Siqueira, Camila Renata Correa, Joelcio Francisco Abbade and Valeria Cristina Sandrim

Antioxidants 2022, 11(8), 1620; https://doi.org/10.3390/antiox11081620 - 20 Aug 2022

Cited by 5 | Viewed by 2189

Abstract

(1) Background: The bioavailability of nitric oxide (NO) and oxidative stress are important events related to the pathophysiology of preeclampsia (PE). In this present study, we aimed to evaluate the antioxidant effect of glibenclamide (GB) on the NO synthesis, oxidative stress, and antioxidant [...] Read more.

(1) Background: The bioavailability of nitric oxide (NO) and oxidative stress are important events related to the pathophysiology of preeclampsia (PE). In this present study, we aimed to evaluate the antioxidant effect of glibenclamide (GB) on the NO synthesis, oxidative stress, and antioxidant capacity in endothelial cells incubated with plasma from preeclamptic (PE) and normotensive pregnant women (NT). (2) Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with a plasma pool from 10 NT and 10 PE pregnant women; NO/NOx quantification and ROS levels were assessed by a fluorescence compound; lipid peroxidation was evaluated employing thiobarbituric acid (TBA); and total antioxidant capacity was measured by ferric reduction ability power (FRAP) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). (3) Results: We found that endothelial cells incubated with plasma from PE showed lower NO and NOx levels compared with the NT group. However, GB treatment increased these levels, as well as the antioxidant capacity. Furthermore, a decrease was observed in ROS generation and lipid peroxidation (4) Conclusions: The GB treatment exerted a positive effect on the NO/NOx production by HUVEC incubated with plasma from NT and PE pregnant women, as well as in the reduction in oxidative stress and increase in the antioxidant capacity. Full article

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16 pages, 827 KiB

Open AccessReview

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

by Thi Thuy Tien Vo, Thao Duy Huynh, Ching-Shuen Wang, Kuei-Hung Lai, Zih-Chan Lin, Wei-Ning Lin, Yuh-Lien Chen, Tzu-Yu Peng, Ho-Cheng Wu and I-Ta Lee

Antioxidants 2022, 11(8), 1619; https://doi.org/10.3390/antiox11081619 - 20 Aug 2022

Cited by 12 | Viewed by 3107

Abstract

The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed [...] Read more.

The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H₂S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H₂S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H₂S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H₂S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H₂S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism. Full article

(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)

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18 pages, 3581 KiB

Open AccessArticle

A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro

by Sung-Sook Choi, Sun-Hyung Lee and Kyung-Ae Lee

Antioxidants 2022, 11(8), 1618; https://doi.org/10.3390/antiox11081618 - 20 Aug 2022

Cited by 82 | Viewed by 6029

Abstract

The antioxidant, anti-inflammatory and antibacterial activities of hesperetin, hesperidin and hesperidin glucoside with different solubility were compared in vitro. Hesperetin was prepared by enzymatic hydrolysis from hesperidin, and hesperidin glucoside composed of hesperidin mono-glucoside was prepared from hesperidin through enzymatic transglycosylation. Solubility of [...] Read more.

The antioxidant, anti-inflammatory and antibacterial activities of hesperetin, hesperidin and hesperidin glucoside with different solubility were compared in vitro. Hesperetin was prepared by enzymatic hydrolysis from hesperidin, and hesperidin glucoside composed of hesperidin mono-glucoside was prepared from hesperidin through enzymatic transglycosylation. Solubility of the compounds was different: the partition coefficient (log P) was 2.85 ± 0.02 for hesperetin, 2.01 ± 0.02 for hesperidin, and −3.04 ± 0.03 for hesperidin glucoside. Hesperetin showed a higher effect than hesperidin and hesperidin glucoside on radical scavenging activity in antioxidant assays, while hesperidin and hesperidin glucoside showed similar activity. Cytotoxicity was low in the order of hesperidin glucoside, hesperidin, and hesperetin in murine macrophage RAW264.7 cells. Treatment of the cells with each compound reduced the levels of inflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Hesperetin was most effective at relatively low concentrations, however, hesperidin glucoside was also effective at higher concentration. Hesperetin showed higher antibacterial activity than hesperidin in both Gram-positive and -negative bacteria, and hesperidin glucoside showed similarly higher activity with hesperetin depending on the bacterial strain. In conclusion, hesperetin in the form of aglycone showed more potent biological activity than hesperidin and hesperidin glucoside. However, hesperidin glucoside, the highly soluble form, has been shown to increase the activity compared to poorly soluble hesperidin. Full article

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22 pages, 1060 KiB

Open AccessReview

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

by Irma Virant-Klun, Senka Imamovic-Kumalic and Bojana Pinter

Antioxidants 2022, 11(8), 1617; https://doi.org/10.3390/antiox11081617 - 20 Aug 2022

Cited by 35 | Viewed by 5578

Abstract

Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and [...] Read more.

Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and testicular germ-cell, prostate, and breast cancers. We conducted an electronic search using PubMed on endocrine disruptors related to oxidative stress and male infertility, and evaluated their association with endocrine-disrupting chemicals (bisphenols, phthalates, and parabens) in 25 articles. Higher levels of urinary bisphenols showed correlation with impaired semen quality and increased DNA damage. Considering phthalates and their metabolites, all studies found a positive association between urinary levels of phthalates and at least one semen parameter indicative of low semen quality; some studies also revealed sperm DNA damage. The studies on parabens less often revealed correlation of urinary parabens concentrations with a decrease in sperm count, as well as motility and DNA damage. Moreover, EDCs can elevate ROS production and lipid peroxidation, increase apoptosis, induce epigenetic modifications, and change the Y:X sperm chromosome ratio and sperm protein composition. Our review revealed detrimental effects of EDCs on semen quality and sperm DNA integrity—especially in BPA and phthalates, but also in parabens. Full article

(This article belongs to the Special Issue Sperm Oxidative Stress)

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22 pages, 4583 KiB

Open AccessArticle

Activation and Inhibition of Human Matrix Metalloproteinase-9 (MMP9) by HOCl, Myeloperoxidase and Chloramines

by Yihe Wang, Christine Y. Chuang, Clare L. Hawkins and Michael J. Davies

Antioxidants 2022, 11(8), 1616; https://doi.org/10.3390/antiox11081616 - 20 Aug 2022

Cited by 8 | Viewed by 3363

Abstract

Matrix metalloproteinase-9 (MMP9, gelatinase B) plays a key role in the degradation of extracellular-matrix (ECM) proteins in both normal physiology and multiple pathologies, including those linked with inflammation. MMP9 is excreted as an inactive proform (proMMP9) by multiple cells, and particularly neutrophils. The [...] Read more.

Matrix metalloproteinase-9 (MMP9, gelatinase B) plays a key role in the degradation of extracellular-matrix (ECM) proteins in both normal physiology and multiple pathologies, including those linked with inflammation. MMP9 is excreted as an inactive proform (proMMP9) by multiple cells, and particularly neutrophils. The proenzyme undergoes subsequent processing to active forms, either enzymatically (e.g., via plasmin and stromelysin-1/MMP3), or via the oxidation of a cysteine residue in the prodomain (the “cysteine-switch”). Activated leukocytes, including neutrophils, generate O₂⁻ and H₂O₂ and release myeloperoxidase (MPO), which catalyzes hypochlorous acid (HOCl) formation. Here, we examine the reactivity of HOCl and a range of low-molecular-mass and protein chloramines with the pro- and activated forms of MMP9. HOCl and an enzymatic MPO/H₂O₂/Cl⁻ system were able to generate active MMP9, as determined by fluorescence-activity assays and gel zymography. The inactivation of active MMP9 also occurred at high HOCl concentrations. Low (nM—low μM) concentrations of chloramines formed by the reaction of HOCl with amino acids (taurine, lysine, histidine), serum albumin, ECM proteins (laminin and fibronectin) and basement membrane extracts (but not HEPES chloramines) also activate proMMP9. This activation is diminished by the competitive HOCl-reactive species, methionine. These data indicate that HOCl-mediated oxidation and MMP-mediated ECM degradation are synergistic and interdependent. As previous studies have shown that modified ECM proteins can also stimulate the cellular expression of MMP proteins, these processes may contribute to a vicious cycle of increasing ECM degradation during disease development. Full article

(This article belongs to the Special Issue Heme Peroxidases in (Patho)Physiological Reactions and Disease Progression)

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15 pages, 1722 KiB

Open AccessArticle

Oxidative Implications of Substituting a Conserved Cysteine Residue in Sugar Beet Phytoglobin BvPgb 1.2

by Simon Christensen, Leonard Groth, Nélida Leiva-Eriksson, Maria Nyblom and Leif Bülow

Antioxidants 2022, 11(8), 1615; https://doi.org/10.3390/antiox11081615 - 20 Aug 2022

Cited by 4 | Viewed by 1938

Abstract

Phytoglobins (Pgbs) are plant-originating heme proteins of the globin superfamily with varying degrees of hexacoordination. Pgbs have a conserved cysteine residue, the role of which is poorly understood. In this paper, we investigated the functional and structural role of cysteine in BvPgb1.2, a [...] Read more.

Phytoglobins (Pgbs) are plant-originating heme proteins of the globin superfamily with varying degrees of hexacoordination. Pgbs have a conserved cysteine residue, the role of which is poorly understood. In this paper, we investigated the functional and structural role of cysteine in BvPgb1.2, a Class 1 Pgb from sugar beet (Beta vulgaris), by constructing an alanine-substituted mutant (Cys86Ala). The substitution had little impact on structure, dimerization, and heme loss as determined by X-ray crystallography, size-exclusion chromatography, and an apomyoglobin-based heme-loss assay, respectively. The substitution significantly affected other important biochemical properties. The autoxidation rate increased 16.7- and 14.4-fold for the mutant versus the native protein at 25 °C and 37 °C, respectively. Thermal stability similarly increased for the mutant by ~2.5 °C as measured by nano-differential scanning fluorimetry. Monitoring peroxidase activity over 7 days showed a 60% activity decrease in the native protein, from 33.7 to 20.2 U/mg protein. When comparing the two proteins, the mutant displayed a remarkable enzymatic stability as activity remained relatively constant throughout, albeit at a lower level, ~12 U/mg protein. This suggests that cysteine plays an important role in BvPgb1.2 function and stability, despite having seemingly little effect on its tertiary and quaternary structure. Full article

(This article belongs to the Special Issue Globin Associated Oxidative Stress)

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13 pages, 2026 KiB

Open AccessArticle

Effects of the Partial Substitution of Corn with Wheat or Barley on the Growth Performance, Blood Antioxidant Capacity, Intestinal Health and Fecal Microbial Composition of Growing Pigs

by Xiaokang Ma, Zhiqing Li and Yuebo Zhang

Antioxidants 2022, 11(8), 1614; https://doi.org/10.3390/antiox11081614 - 20 Aug 2022

Cited by 6 | Viewed by 1867

Abstract

This experiment aimed to investigate the effects of wheat and barley substitution for corn on growth performance, blood antioxidant capacity, intestinal health and fecal microbial composition in growing pigs. Eighteen healthy “Duroc × Landrace × Yorkshire” pigs (50 ± 0.85 kg) were randomly [...] Read more.

This experiment aimed to investigate the effects of wheat and barley substitution for corn on growth performance, blood antioxidant capacity, intestinal health and fecal microbial composition in growing pigs. Eighteen healthy “Duroc × Landrace × Yorkshire” pigs (50 ± 0.85 kg) were randomly divided into three groups with six replicates and one pig per replicate. The three treatment groups were fed the basal diet (CON) based on corn and soybean meal, respectively, and the experimental group diet was partially replaced by wheat (WH) and barley (BL), respectively. The nutritional levels of the three treatments were the same. The experiment lasted 28 days. Wheat and barley partially replacing corn had no significant effects on growing pigs’ growth performance, blood antioxidant capacity and nutrient digestibility (p > 0.05). Compared with CON and BL, WH significantly increased the duodenal villus height and villus height/crypt depth ratio of growing pigs (p < 0.05). Compared with CON, WH and BL significantly increased the contents of butyric acid, propionic acid and total volatile fatty acid (VFA) in the cecum and colonic digesta of growing pigs (p < 0.05). In addition, the abundance of Turicibacter, Escherichia-Shigella and other harmful bacteria in barley and wheat diet groups were significantly decreased at the genus level (p < 0.05). The abundance of Bifidobacterium, Lactobacillus, Prevotella and Roseburia increased significantly (p < 0.05). In conclusion, barley and wheat partially replacing corn as energy feedstuffs does not affect the growth performance of pigs but can regulate intestinal flora and promote intestinal health. Full article

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28 pages, 1120 KiB

Open AccessReview

Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation

by Mariapaola Nitti, Barbara Marengo, Anna Lisa Furfaro, Maria Adelaide Pronzato, Umberto Maria Marinari, Cinzia Domenicotti and Nicola Traverso

Antioxidants 2022, 11(8), 1613; https://doi.org/10.3390/antiox11081613 - 19 Aug 2022

Cited by 17 | Viewed by 4074

Abstract

Alterations of redox homeostasis leads to a condition of resilience known as hormesis that is due to the activation of redox-sensitive pathways stimulating cell proliferation, growth, differentiation, and angiogenesis. Instead, supraphysiological production of reactive oxygen species (ROS) exceeds antioxidant defence and leads to [...] Read more.

Alterations of redox homeostasis leads to a condition of resilience known as hormesis that is due to the activation of redox-sensitive pathways stimulating cell proliferation, growth, differentiation, and angiogenesis. Instead, supraphysiological production of reactive oxygen species (ROS) exceeds antioxidant defence and leads to oxidative distress. This condition induces damage to biomolecules and is responsible or co-responsible for the onset of several chronic pathologies. Thus, a dietary antioxidant supplementation has been proposed in order to prevent aging, cardiovascular and degenerative diseases as well as carcinogenesis. However, this approach has failed to demonstrate efficacy, often leading to harmful side effects, in particular in patients affected by cancer. In this latter case, an approach based on endogenous antioxidant depletion, leading to ROS overproduction, has shown an interesting potential for enhancing susceptibility of patients to anticancer therapies. Therefore, a deep investigation of molecular pathways involved in redox balance is crucial in order to identify new molecular targets useful for the development of more effective therapeutic approaches. The review herein provides an overview of the pathophysiological role of ROS and focuses the attention on positive and negative aspects of antioxidant modulation with the intent to find new insights for a successful clinical application. Full article

(This article belongs to the Special Issue Role of Oxidative Stress and Antioxidants in Pathophysiology: A Commemorative Special Issue in Honour of Professor Mario Umberto Dianzani)

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18 pages, 1658 KiB

Open AccessArticle

Evaluation of Plant Protein Hydrolysates as Natural Antioxidants in Fish Oil-In-Water Emulsions

by Jeimmy Lizeth Ospina-Quiroga, Pedro J. García-Moreno, Antonio Guadix, Emilia M. Guadix, María del Carmen Almécija-Rodríguez and Raúl Pérez-Gálvez

Antioxidants 2022, 11(8), 1612; https://doi.org/10.3390/antiox11081612 - 19 Aug 2022

Cited by 7 | Viewed by 2707

Abstract

In this work, we evaluated the physical and oxidative stabilities of 5% w/w fish oil-in-water emulsions stabilized with 1%wt Tween20 and containing 2 mg/mL of protein hydrolysates from olive seed (OSM–H), sunflower (SFSM–H), rapeseed (RSM–H) and lupin (LUM–H) meals. To this end, the [...] Read more.

In this work, we evaluated the physical and oxidative stabilities of 5% w/w fish oil-in-water emulsions stabilized with 1%wt Tween20 and containing 2 mg/mL of protein hydrolysates from olive seed (OSM–H), sunflower (SFSM–H), rapeseed (RSM–H) and lupin (LUM–H) meals. To this end, the plant-based substrates were hydrolyzed at a 20% degree of hydrolysis (DH) employing a mixture 1:1 of subtilisin: trypsin. The hydrolysates were characterized in terms of molecular weight profile and in vitro antioxidant activities (i.e., DPPH scavenging and ferrous ion chelation). After incorporation of the plant protein hydrolysates as water-soluble antioxidants in the emulsions, a 14-day storage study was conducted to evaluate both the physical (i.e., ζ-potential, droplet size and emulsion stability index) and oxidative (e.g., peroxide and anisidine value) stabilities. The highest in vitro DPPH scavenging and iron (II)-chelating activities were exhibited by SFSM–H (IC₅₀ = 0.05 ± 0.01 mg/mL) and RSM–H (IC₅₀ = 0.41 ± 0.06 mg/mL). All the emulsions were physically stable within the storage period, with ζ-potential values below −35 mV and an average mean diameter D[4,3] of 0.411 ± 0.010 μm. Although LUM–H did not prevent lipid oxidation in emulsions, OSM–H and SFSM–H exhibited a remarkable ability to retard the formation of primary and secondary lipid oxidation products during storage when compared with the control emulsion without antioxidants. Overall, our findings show that plant-based enzymatic hydrolysates are an interesting alternative to be employed as natural antioxidants to retard lipid oxidation in food emulsions. Full article

(This article belongs to the Special Issue Antioxidant Properties and Potential Mechanisms of Protein Hydrolysates)

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18 pages, 3590 KiB

Open AccessArticle

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

by Elisa Martino, Anna Balestrieri, Camilla Anastasio, Martina Maione, Luigi Mele, Domenico Cautela, Giuseppe Campanile, Maria Luisa Balestrieri and Nunzia D’Onofrio

Antioxidants 2022, 11(8), 1611; https://doi.org/10.3390/antiox11081611 - 19 Aug 2022

Cited by 17 | Viewed by 3054

Abstract

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative [...] Read more.

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p < 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p < 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3⁺) suppressed the PA-induced autophagy (mimic NC+PA) (p < 0.01), inflammation, and pyroptosis (p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries. Full article

(This article belongs to the Topic Redox Metabolism)

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22 pages, 2472 KiB

Open AccessArticle

Basic Cognition of Melatonin Regulation of Plant Growth under Salt Stress: A Meta-Analysis

by Feiyu Yan, Hongliang Zhao, Longmei Wu, Zhiwei Huang, Yuan Niu, Bo Qi, Linqing Zhang, Song Fan, Yanfeng Ding, Ganghua Li and Guoliang Zhang

Antioxidants 2022, 11(8), 1610; https://doi.org/10.3390/antiox11081610 - 19 Aug 2022

Cited by 5 | Viewed by 2337

Abstract

Salt stress severely restricts the growth of plants and threatens the development of agriculture throughout the world. Worldwide studies have shown that exogenous melatonin (MT) can effectively improve the growth of plants under salt stress. Through a meta-analysis of 549 observations, this study [...] Read more.

Salt stress severely restricts the growth of plants and threatens the development of agriculture throughout the world. Worldwide studies have shown that exogenous melatonin (MT) can effectively improve the growth of plants under salt stress. Through a meta-analysis of 549 observations, this study first explored the effects of salt stress characteristics and MT application characteristics on MT regulated plant growth under salt stress. The results show that MT has a wide range of regulatory effects on plant growth indicators under salt stress, of which the regulatory effect on root indexes is the strongest, and this regulatory effect is not species-specific. The intensity of salt stress did not affect the positive effect of MT on plant growth, but the application effect of MT in soil was stronger than that in rooting medium. This meta-analysis also revealed that the foliar application of a concentration between 100–200 μM is the best condition for MT to enhance plant growth under salt stress. The results can inspire scientific research and practical production, while seeking the maximum improvement in plant salt tolerance under salt stress. Full article

(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)

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37 pages, 2299 KiB

Open AccessSystematic Review

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

by Evangelia Eirini Tsermpini, Una Glamočlija, Fulden Ulucan-Karnak, Sara Redenšek Trampuž and Vita Dolžan

Antioxidants 2022, 11(8), 1609; https://doi.org/10.3390/antiox11081609 - 19 Aug 2022

Cited by 21 | Viewed by 4776

Abstract

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease’s progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx [...] Read more.

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease’s progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine. Full article

(This article belongs to the Special Issue Oxidative Stress, Inflammatory Signaling, Nutrition and COVID-19)

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22 pages, 4532 KiB

Open AccessArticle

Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model

by Álvaro Santana-Garrido, Claudia Reyes-Goya, Pablo Espinosa-Martín, Luis Sobrevia, Luis M. Beltrán, Carmen M. Vázquez and Alfonso Mate

Antioxidants 2022, 11(8), 1608; https://doi.org/10.3390/antiox11081608 - 19 Aug 2022

Cited by 11 | Viewed by 3035

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the new onset of hypertension plus proteinuria and/or end-organ dysfunction. Here, we investigate the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system as a major component of reactive oxygen species generation, in a [...] Read more.

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the new onset of hypertension plus proteinuria and/or end-organ dysfunction. Here, we investigate the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system as a major component of reactive oxygen species generation, in a rodent model of early-onset preeclampsia induced by excess sFlt1 (soluble fms-like tyrosine kinase 1). Placenta and kidney samples were obtained from normal pregnant and PE rats to measure the sFlt1/PlGF (placental growth factor) ratio in addition to oxidative stress-related parameters, including the activities and expressions of NADPH oxidase isoforms (NOX1, NOX2, and NOX4), components of nitric oxide (NO) metabolism, and antioxidant enzymes. Peroxisome proliferator-activated receptors (PPARα, PPARγ) and cytokines IL1β, IL3, IL6, IL10, and IL18 were also measured to evaluate the inflammation status in our experimental setting. Excessive O₂^●− production was found in rats that were treated with sFlt1; interestingly, this alteration appears to be mediated mainly by NOX2 in the placenta and by NOX4 in the kidney. Altered NO metabolism and antioxidant defense systems, together with mitochondrial dysfunction, were observed in this model of PE. Preeclamptic animals also exhibited overexpression of proinflammatory biomarkers as well as increased collagen deposition. Our results highlight the role of NADPH oxidase in mediating oxidative stress and possibly inflammatory processes in the placenta and kidney of an sFlt1-based model of early-onset preeclampsia. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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23 pages, 3700 KiB

Open AccessArticle

Metabolic and Structural Insights into Hydrogen Sulfide Mis-Regulation in Enterococcus faecalis

by Brenna J. C. Walsh, Sofia Soares Costa, Katherine A. Edmonds, Jonathan C. Trinidad, Federico M. Issoglio, José A. Brito and David P. Giedroc

Antioxidants 2022, 11(8), 1607; https://doi.org/10.3390/antiox11081607 - 19 Aug 2022

Cited by 8 | Viewed by 3511

Abstract

Hydrogen sulfide (H₂S) is implicated as a cytoprotective agent that bacteria employ in response to host-induced stressors, such as oxidative stress and antibiotics. The physiological benefits often attributed to H₂S, however, are likely a result of downstream, more oxidized [...] Read more.

Hydrogen sulfide (H₂S) is implicated as a cytoprotective agent that bacteria employ in response to host-induced stressors, such as oxidative stress and antibiotics. The physiological benefits often attributed to H₂S, however, are likely a result of downstream, more oxidized forms of sulfur, collectively termed reactive sulfur species (RSS) and including the organic persulfide (RSSH). Here, we investigated the metabolic response of the commensal gut microorganism Enterococcus faecalis to exogenous Na₂S as a proxy for H₂S/RSS toxicity. We found that exogenous sulfide increases protein abundance for enzymes responsible for the biosynthesis of coenzyme A (CoA). Proteome S-sulfuration (persulfidation), a posttranslational modification implicated in H₂S signal transduction, is also widespread in this organism and is significantly elevated by exogenous sulfide in CstR, the RSS sensor, coenzyme A persulfide (CoASSH) reductase (CoAPR) and enzymes associated with de novo fatty acid biosynthesis and acetyl-CoA synthesis. Exogenous sulfide significantly impacts the speciation of fatty acids as well as cellular concentrations of acetyl-CoA, suggesting that protein persulfidation may impact flux through these pathways. Indeed, CoASSH is an inhibitor of E. faecalis phosphotransacetylase (Pta), suggesting that an important metabolic consequence of increased levels of H₂S/RSS may be over-persulfidation of this key metabolite, which, in turn, inhibits CoA and acyl-CoA-utilizing enzymes. Our 2.05 Å crystallographic structure of CoA-bound CoAPR provides new structural insights into CoASSH clearance in E. faecalis. Full article

(This article belongs to the Special Issue Reactive Sulfur Species in Biology and Medicine)

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17 pages, 8203 KiB

Open AccessArticle

Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches

by Yoo Lim Chun, Won-Joon Eom, Jun Hyung Lee, Thy N. C. Nguyen, Ki-Hoon Park, Hyung-Joo Chung, Han Seo, Youngbuhm Huh, Sang Hoon Kim, Seung Geun Yeo, Wonseok Park, Geul Bang, Jin Young Kim, Min-Sik Kim, Na Young Jeong and Junyang Jung

Antioxidants 2022, 11(8), 1606; https://doi.org/10.3390/antiox11081606 - 19 Aug 2022

Cited by 3 | Viewed by 2690

Abstract

N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H₂S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H₂S [...] Read more.

N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H₂S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H₂S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H₂S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H₂S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H₂S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation. Full article

(This article belongs to the Special Issue Hydrogen Sulfide and Diseases)

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12 pages, 686 KiB

Open AccessSystematic Review

A Systematic Review on the Role of Vitamin C in Tissue Healing

by Nada Bechara, Victoria M. Flood and Jenny E. Gunton

Antioxidants 2022, 11(8), 1605; https://doi.org/10.3390/antiox11081605 - 19 Aug 2022

Cited by 24 | Viewed by 10840

Abstract

Vitamin C is an essential nutrient for humans and animals which are unable to synthesise it themselves. Vitamin C is important for tissue regeneration due to the role it plays in collagen formation, and its antioxidant properties. We reviewed the literature to evaluate [...] Read more.

Vitamin C is an essential nutrient for humans and animals which are unable to synthesise it themselves. Vitamin C is important for tissue regeneration due to the role it plays in collagen formation, and its antioxidant properties. We reviewed the literature to evaluate potential associations between vitamin C supplementation and healing of an acute or chronic condition. Embase, Medline, PubMed, and the Cochrane Library were searched for studies published prior to April 2022. Studies were eligible if they reported at least one association between vitamin C supplementation and healing outcomes. Eighteen studies met the inclusion criteria and were included in this review. Overall, vitamin C supplementation improved healing outcomes in certain pathologies, predominantly pressure ulcers. However, many of the studies had small sample sizes, combined nutritional treatments, and did not test baseline vitamin C. Future studies should be of larger scale, exclusively using vitamin C to determine its role in tissue healing in other wounds. We recommend consideration of vitamin C supplementation for people with pressure ulcers. Full article

(This article belongs to the Special Issue Antioxidants in Fruits and Vegetables)

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15 pages, 3201 KiB

Open AccessArticle

Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria

by Karina D. Hamilton, Daniel Czajkowski, Nicolas J. Kong, Trong D. Tran, Kirk R. Gustafson, Gary Pauly, Glen M. Boyle, Jacinta L. Simmons, Robert Steadman, Ryan Moseley, Peter R. Brooks, Steven M. Ogbourne and Fraser D. Russell

Antioxidants 2022, 11(8), 1604; https://doi.org/10.3390/antiox11081604 - 19 Aug 2022

Cited by 2 | Viewed by 1890

Abstract

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and [...] Read more.

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5–25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-β₁ (TGF-β₁)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC₅₀ value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1). Full article

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24 pages, 2908 KiB

Open AccessArticle

Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach

by Severina Pacifico, Pavel Bláha, Shadab Faramarzi, Francesca Fede, Katarina Michaličková, Simona Piccolella, Valerio Ricciardi and Lorenzo Manti

Antioxidants 2022, 11(8), 1603; https://doi.org/10.3390/antiox11081603 - 19 Aug 2022

Cited by 8 | Viewed by 2301

Abstract

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf [...] Read more.

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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21 pages, 6454 KiB

Open AccessArticle

D-Penicillamine Reveals the Amelioration of Seizure-Induced Neuronal Injury via Inhibiting Aqp11-Dependent Ferroptosis

by Nan Yang, Kai Zhang, Qi-Wen Guan, Zhao-Jun Wang, Kang-Ni Chen and Xiao-Yuan Mao

Antioxidants 2022, 11(8), 1602; https://doi.org/10.3390/antiox11081602 - 19 Aug 2022

Cited by 11 | Viewed by 3789

Abstract

Repetitive seizures, a common phenomenon in diverse neurologic conditions such as epilepsy, can undoubtedly cause neuronal injury and our prior work reveals that ferroptosis is a contributing factor of neuronal damage post seizure. However, there is no drug available in clinical practice for [...] Read more.

Repetitive seizures, a common phenomenon in diverse neurologic conditions such as epilepsy, can undoubtedly cause neuronal injury and our prior work reveals that ferroptosis is a contributing factor of neuronal damage post seizure. However, there is no drug available in clinical practice for ameliorating seizure-induced neuronal impairment via targeting ferroptosis. Our present work aimed to explore whether D-penicillamine (DPA), an originally approved drug for treating Wilson’s disease, inhibited neuronal ferroptosis and alleviated seizure-associated brain damage. Our findings revealed that DPA remarkably improved neuronal survival in kainic acid (KA)-treated mouse model. Furthermore, ferroptosis-associated indices including acyl-coA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (Ptgs2) gene and lipid peroxide (LPO) level were significantly decreased in KA mouse model after DPA treatment. In a ferroptotic cell death model induced by glutamate or erastin, DPA was also validated to evidently suppress neuronal ferroptosis. The results from RNA-seq analysis indicated that Aqp11, a gene coding previously reported channel protein responsible for transporting water and small solutes, was identified as a molecular target by which DPA exerted anti-ferroptotic potential in neurons. The experimental results from in vivo Aqp11 siRNA transfer into the brain also confirmed that knockdown of Aqp11 abrogated the inhibitory effect of seizure-induced ferroptosis after DPA treatment, suggesting that the effects of DPA on ferroptosis process are dependent upon Aqp11. In conclusion, DPA can be repurposed to cure seizure disorders such as epilepsy. Full article

(This article belongs to the Special Issue Ferroptosis and Its Potential Role in the Physiopathology of Brain Injury)

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35 pages, 9329 KiB

Open AccessArticle

Evaluation of Usnea barbata (L.) Weber ex F.H. Wigg Extract in Canola Oil Loaded in Bioadhesive Oral Films for Potential Applications in Oral Cavity Infections and Malignancy

by Violeta Popovici, Elena Matei, Georgeta Camelia Cozaru, Laura Bucur, Cerasela Elena Gîrd, Verginica Schröder, Emma Adriana Ozon, Oana Karampelas, Adina Magdalena Musuc, Irina Atkinson, Adriana Rusu, Simona Petrescu, Raul-Augustin Mitran, Mihai Anastasescu, Aureliana Caraiane, Dumitru Lupuliasa, Mariana Aschie and Victoria Badea

Antioxidants 2022, 11(8), 1601; https://doi.org/10.3390/antiox11081601 - 19 Aug 2022

Cited by 15 | Viewed by 4858

Abstract

Usnea lichens are known for their beneficial pharmacological effects with potential applications in oral medicine. This study aims to investigate the extract of Usnea barbata (L.) Weber ex F.H. Wigg from the Călimani Mountains in canola oil as an oral pharmaceutical formulation. In [...] Read more.

Usnea lichens are known for their beneficial pharmacological effects with potential applications in oral medicine. This study aims to investigate the extract of Usnea barbata (L.) Weber ex F.H. Wigg from the Călimani Mountains in canola oil as an oral pharmaceutical formulation. In the present work, bioadhesive oral films (F-UBO) with U. barbata extract in canola oil (UBO) were formulated, characterized, and evaluated, evidencing their pharmacological potential. The UBO-loaded films were analyzed using standard methods regarding physicochemical and pharmacotechnical characteristics to verify their suitability for topical administration on the oral mucosa. F-UBO suitability confirmation allowed for the investigation of antimicrobial and anticancer potential. The antimicrobial properties against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019 were evaluated by a resazurin-based 96-well plate microdilution method. The brine shrimp lethality assay (BSL assay) was the animal model cytotoxicity prescreen, followed by flow cytometry analyses on normal blood cells and oral epithelial squamous cell carcinoma CLS-354 cell line, determining cellular apoptosis, caspase-3/7 activity, nuclear condensation and lysosomal activity, oxidative stress, cell cycle, and cell proliferation. The results indicate that a UBO-loaded bioadhesive film’s weight is 63 ± 1.79 mg. It contains 315 µg UBO, has a pH = 6.97 ± 0.01, a disintegration time of 124 ± 3.67 s, and a bioadhesion time of 86 ± 4.12 min, being suitable for topical administration on the oral mucosa. F-UBO showed moderate dose-dependent inhibitory effects on the growth of both bacterial and fungal strains. Moreover, in CLS-354 tumor cells, F-UBO increased oxidative stress, diminished DNA synthesis, and induced cell cycle arrest in G0/G1. All these properties led to considering UBO-loaded bioadhesive oral films as a suitable phytotherapeutic formulation with potential application in oral infections and neoplasia. Full article

(This article belongs to the Special Issue Natural Antioxidants and Oral Health)

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Antioxidants, Volume 11, Issue 8 (August 2022) – 212 articles

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