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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 25474

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Special Issue Editors

Dr. Milagros Rocha

E-Mail Website1 Website2 Website3
Guest Editor

1. Dr. Peset Hospital Research Foundation, Valencia, Spain
2.CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, University of Valencia, Valencia, Spain
Interests: oxidative stress; obesity; inflammation; endothelial dysfunction; endoplasmic reticulum stress
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Victor M. Victor

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Co-Guest Editor

Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain
Interests: mitochondria; autophagy; type 2 diabetes; oxidative stress; mitophagy; insulin resistance; atherosclerosis

Dr. Sandra López-Doménech

E-Mail Website
Co-Guest Editor

University Hospital Doctor Peset-FISABIO, Valencia, Spain
Interests: mitochondrial dysfunction; oxidative stress; inflammation; atherosclerosis; obesity

Special Issue Information

Dear Colleagues,

Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus, obesity, metabolic syndrome, and fatty liver diseases, has increased dramatically. Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between the generation of reactive ROS and antioxidant defense systems establishes oxidative stress. Previous studies have found that excessive ROS generation is linked to cellular and tissue dysfunction, immune activation, and inflammation that are critical for the pathogenesis of metabolic diseases. Underlying molecular mechanisms leading to oxidative-induced cellular dysfunction include mitochondrial impairment, autophagy, mitophagy, endoplasmic reticulum stress and apoptosis, but there is still much to be learned about their mutual interaction and the modifications they undergo during metabolic diseases. Given the relevance of this topic, it would seem appropriate to summarize some of the main recent advances in the research on the role of oxidative stress and underlying molecular mechanisms in the pathogenesis of metabolic diseases and the new therapeutic strategies to combat their detrimental impact on health, disease and ageing.

Authors are invited to submit both original and review articles related, but not limited, to these interesting topics.

Dr. Milagros Rocha
Guest Editor
Dr. Victor M. Victor
Dr. Sandra López-Doménech
Co-Guest Editors

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Keywords

mitochondrial dysfunction
insulin resistance
inflammation
autophagy
mitophagy
ER stress
apoptosis
liver
adipose tissue
muscle
pancreatic cells

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Published Papers (7 papers)

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18 pages, 5988 KiB

Open AccessArticle

β-Cell Autophagy Pathway and Endoplasmic Reticulum Stress Regulating-Role of Liposomal Curcumin in Experimental Diabetes Mellitus: A Molecular and Morphometric Study

by Safaa I. Khater, Mohamed F. Dowidar, Aya E. Abdel-Aziz, Tarek Khamis, Naief Dahran, Leena S. Alqahtani, Mohamed M. M. Metwally, Al-Sayed Al-Hady Abd-Elrahamn, Mohammed Alsieni, Manal E. Alosaimi, Maram H. Abduljabbar and Amany Abdel-Rahman Mohamed

Antioxidants 2022, 11(12), 2400; https://doi.org/10.3390/antiox11122400 - 2 Dec 2022

Cited by 14 | Viewed by 2598

Abstract

Background: Autophagy can confer protection to pancreatic β-cells from the harmful effects of metabolic stress by delaying apoptosis. Curcumin (CUR) alleviates oxidative and endoplasmic reticulum (ER) stress, activates autophagy, reduces inflammation, and decreases β-cell damage in type I diabetes. Liposomal CUR (LPs-CUR) has a higher therapeutic value and better pharmacokinetics than CUR. Objectives: We determined LPs-CUR’s ability to alleviate stress, reduce β-cell damage and unraveled the mechanism underlying its protective effect using a streptozotocin (STZ)-induced type I diabetic rat model. Methods: Sprague–Dawley rats were grouped into vehicle control, STZ-diabetic (STZ 65 mg/kg), STZ-diabetic-3-MA (3-methyladenine [3-MA] 10 mg/kg b.wt), STZ. diabetic-LPs-CUR (LPs-CUR 10 mg/kg b.wt), and STZ diabetic-LPs-CUR-3-MA (LPs-CUR 10 mg/kg b.wt; 3-MA 10 mg/kg b.wt). Results: LPs-CUR significantly reduced blood glucose, oxidative stress, and cellular inflammation in the pancreatic tissue (p < 0.001). ER stress-dependent genes included ATF-6, eIF-2, CHOP, JNK, BiP, and XBP LPs-CUR significantly suppressed fold changes, while it upregulated the autophagic markers Beclin-1 and LC3-II. Conclusions: LP-CUR ameliorates β-cell damage by targeting the autophagy pathway with the regulatory miRNAs miR-137 and miR-29b, which functionally abrogates ER stress in β-cells. This study presents a new therapeutic target for managing type I diabetes using miR-137 and miR-29b. Full article

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

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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 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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15 pages, 11979 KiB

Open AccessArticle

Impact of Roux-en-Y Gastric Bypass on Mitochondrial Biogenesis and Dynamics in Leukocytes of Obese Women

by Zaida Abad-Jiménez, Teresa Vezza, Sandra López-Domènech, Meylin Fernández-Reyes, Francisco Canet, Carlos Morillas, Segundo Ángel Gómez-Abril, Celia Bañuls, Víctor M. Víctor and Milagros Rocha

Antioxidants 2022, 11(7), 1302; https://doi.org/10.3390/antiox11071302 - 29 Jun 2022

Cited by 4 | Viewed by 2541

Abstract

The chronic low-grade inflammation widely associated with obesity can lead to a prooxidant status that triggers mitochondrial dysfunction. To date, Roux-en-Y gastric bypass (RYGB) is considered the most effective strategy for obese patients. However, little is known about its molecular mechanisms. This interventional study aimed to investigate whether RYGB modulates oxidative stress, inflammation and mitochondrial dynamics in the leukocytes of 47 obese women at one year follow-up. We evaluated biochemical parameters and serum inflammatory cytokines -TNFα, IL6 and IL1β- to assess systemic status. Total superoxide production -dHe-, mitochondrial membrane potential -TMRM-, leucocyte protein expression of inflammation mediators -MCP1 and NF-kB-, antioxidant defence -GPX1-, mitochondrial regulation—PGC1α, TFAM, OXPHOS and MIEAP- and dynamics -MFN2, MNF1, OPA1, FIS1 and p-DRP1- were also determined. After RYGB, a significant reduction in superoxide and mitochondrial membrane potential was evident, while GPX1 content was significantly increased. Likewise, a marked upregulation of the transcription factors PGC1α and TFAM, complexes of the oxidative phosphorylation chain (I–V) and MIEAP and MFN1 was observed. We conclude that women undergoing RYGB benefit from an amelioration of their prooxidant and inflammatory status and an improvement in mitochondrial dynamics of their leukocytes, which is likely to have a positive effect on clinical outcome. Full article

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

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16 pages, 2973 KiB

Open AccessArticle

Ameliorative and Antioxidative Potential of Lactobacillus plantarum-Fermented Oat (Avena sativa) and Fermented Oat Supplemented with Sidr Honey against Streptozotocin-Induced Type 2 Diabetes in Rats

by Hend F. Alharbi, Raya Algonaiman and Hassan Barakat

Antioxidants 2022, 11(6), 1122; https://doi.org/10.3390/antiox11061122 - 6 Jun 2022

Cited by 17 | Viewed by 3100

Abstract

The ameliorative and antioxidative stress effects of probiotic-enriched fermented oat (FOE) or fermented oat with honey (HFOE) extracts on streptozotocin-induced diabetes in rats were examined. The total phenolic content (TPC) and antioxidant activity (AOA) were increased in FOE and HFOE after 72 h of fermentation, and γ-aminobutyric acid (GABA) reached 7.35 mg 100 g⁻¹ in FOE and 8.49 mg 100 g⁻¹ in HFOE. The β-glucan levels were slightly decreased to 2.45 g 100 g⁻¹ DW in FOE and 2.63 g 100 g⁻¹ DW in HFOE. The antidiabetic and hypolipidemic properties of FOE and HFOE were studied in a designed animal model with seven treated groups for 6 weeks. Groups were treated as follows: group 1 (negative group, NR) and group 2 (diabetic rats, DR) were administered 7 mL distilled water orally per day; group 3 (DR + MET) rats were orally administered 50 mg standard drug Metformin kg⁻¹ daily; group 4 (DR + FOE1) diabetic rats were orally administered 3.5 mL FOE daily; group 5 (DR + FOE2) rats were orally administered 7 mL FOE daily; group 6 (DR + HFOE1) rats were orally administered 3.5 mL HFOE daily; and group 7 (DR + HFOE2) rats were orally administered 7 mL HFOE daily. The HFOE at the high dose had a synergistic effect, lowering random blood glucose (RBG) and fasting blood glucose (FBG). The hypolipidemic potential of HFOE at the high dose was indicated by significant reductions in triglycerides (TG), total cholesterol (CHO), high- and low-density lipoproteins (HDL and LDL), and very-low-density lipoproteins (VLDL). In addition, 7 mL of HFOE improved liver and kidney function more effectively than other fermented extracts or Metformin. As well as the antioxidant enzyme activity, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malonaldehyde (MDA) were significantly enhanced after the administration of HFOE at 7 mL by 68.6%, 71.5%, 55.69%, and 15.98%, respectively, compared to the DR group. In conclusion, administration of L. plantarum-fermented oats supplemented with honey demonstrated antidiabetic effects and a potential approach for controlling glucose levels and lipid profiles, and protecting against oxidative stress. Full article

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

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16 pages, 1190 KiB

Open AccessArticle

Inflammatory and Oxidative Stress Markers Related to Adherence to the Mediterranean Diet in Patients with Metabolic Syndrome

by Maria Magdalena Quetglas-Llabrés, Margalida Monserrat-Mesquida, Cristina Bouzas, Cristina Gómez, David Mateos, Tomàs Ripoll-Vera, Josep A. Tur and Antoni Sureda

Antioxidants 2022, 11(5), 901; https://doi.org/10.3390/antiox11050901 - 1 May 2022

Cited by 22 | Viewed by 3601

Abstract

Metabolic syndrome (MetS) is characterized by increased pro-oxidative stress and a pro-inflammatory state. Several studies emphasized the protective effect of the Mediterranean dietary pattern (MDP). To assess the oxidative and inflammatory state according to the adherence to MDP using biomarkers in patients with MetS. Antioxidant and pro-inflammatory biomarkers were determined in plasma, peripheral blood mononuclear cells (PBMCs), and neutrophils of adults (aged 55–75 years old; 60% women) with MetS living in Mallorca (Spain). Anthropometrics, dietary intake by a validated semi-quantitative 143-item food frequency questionnaire, and a Dietary Inflammatory Index were measured. Patients with low adherence to MDP showed higher levels of glycated haemoglobin A1c and triglycerides, and lower levels of HDL cholesterol. Plasma levels of interleukin-1β, IL-6, IL-15, tumour necrosis factor α, xanthine oxidase, and ghrelin, and activities of superoxide dismutase, and myeloperoxidase were higher in subjects with low adherence to the MDP. Reactive oxygen species production in PBMCs and neutrophils stimulated with lipopolysaccharide was higher in participants with low adherence to the MDP. Patients with MetS and higher adherence to the MDP showed less altered anthropometric parameters, blood biochemical profile, and better oxidative and inflammatory status. Full article

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

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24 pages, 6216 KiB

Open AccessFeature PaperArticle

The Symbiotic Effect of a New Nutraceutical with Yeast β-Glucan, Prebiotics, Minerals, and Silybum marianum (Silymarin) for Recovering Metabolic Homeostasis via Pgc-1α, Il-6, and Il-10 Gene Expression in a Type-2 Diabetes Obesity Model

by Aline Boveto Santamarina, Ruan Carlos Macêdo Moraes, Victor Nehmi Filho, Gilson Masahiro Murata, Jéssica Alves de Freitas, Danielle Araujo de Miranda, Anderson Romério Azevedo Cerqueira, Soraia Katia Pereira Costa, Ana Flávia Fernandes Ferreira, Luiz Roberto Britto, Juliana Alves de Camargo, Daniela Rodrigues de Oliveira, Flavia Neto de Jesus, José Pinhata Otoch and Ana Flávia Marçal Pessoa

Antioxidants 2022, 11(3), 447; https://doi.org/10.3390/antiox11030447 - 23 Feb 2022

Cited by 8 | Viewed by 4313

Abstract

The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days). We evaluated the energy homeostasis, cytokines, and mitochondrial gene expression in these groups of mice. After four weeks of supplementation, only the new nutraceutical group (HFD + Supplemented) experienced reduced fasting glycemia, insulin, HOMA index, HOMA-β, dyslipidemia, ectopic fat deposition, and hepatic fibrosis levels. Additionally, the PPARγ coactivator 1 α (Pgc-1α), interleukin-6 (Il-6), and interleukin-10 (Il-10) gene expression were augmented, while hepatic steatosis decreased and liver parenchyma was recovered. The glutathione-S-transferase activity status was found to be modulated by the supplement. We discovered that the new nutraceutical was able to improve insulin resistance and hepatic steatosis mainly by regulating IL-6, IL-10, and Pgc-1α gene expression. Full article

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

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19 pages, 2974 KiB

Open AccessSystematic Review

Potential Molecular Targets of Oleanolic Acid in Insulin Resistance and Underlying Oxidative Stress: A Systematic Review

by Ángel Fernández-Aparicio, María Correa-Rodríguez, Jose M. Castellano, Jacqueline Schmidt-RioValle, Javier S. Perona and Emilio González-Jiménez

Antioxidants 2022, 11(8), 1517; https://doi.org/10.3390/antiox11081517 - 3 Aug 2022

Cited by 13 | Viewed by 3568

Abstract

Oleanolic acid (OA) is a natural triterpene widely found in olive leaves that possesses antioxidant, anti-inflammatory, and insulin-sensitizing properties, among others. These OA characteristics could be of special interest in the treatment and prevention of insulin resistance (IR), but greater in-depth knowledge on the pathways involved in these properties is still needed. We aimed to systematically review the effects of OA on the molecular mechanisms and signaling pathways involved in the development of IR and underlying oxidative stress in insulin-resistant animal models or cell lines. The bibliographic search was carried out on PubMed, Web of Science, Scopus, Cochrane, and CINHAL databases between January 2001 and May 2022. The electronic search produced 5034 articles but, after applying the inclusion criteria, 13 animal studies and 3 cell experiments were identified, using SYRCLE’s Risk of Bias for assessing the risk of bias of the animal studies. OA was found to enhance insulin sensitivity and glucose uptake, and was found to suppress the hepatic glucose production, probably by modulating the IRS/PI3K/Akt/FoxO1 signaling pathway and by mitigating oxidative stress through regulating MAPK pathways. Future randomized controlled clinical trials to assess the potential benefit of OA as new therapeutic and preventive strategies for IR are warranted. Full article

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

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