Antioxidant Roles of SGLT2 Inhibitors in the Kidney

The reduction-oxidation (redox) system consists of the coupling and coordination of various electron gradients that are generated thanks to serial reduction-oxidation enzymatic reactions. These reactions happen in every cell and produce radical oxidants that can be mainly classified into reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS modulate cell-signaling pathways and cellular processes fundamental to normal cell function. However, overproduction of oxidative species can lead to oxidative stress (OS) that is pathological. Oxidative stress is a main contributor to diabetic kidney disease (DKD) onset. In the kidney, the proximal tubular cells require a high energy supply to reabsorb proteins, metabolites, ions, and water. In a diabetic milieu, glucose-induced toxicity promotes oxidative stress and mitochondrial dysfunction, impairing tubular function. Increased glucose level in urine and ROS enhance the activity of sodium/glucose co-transporter type 2 (SGLT2), which in turn exacerbates OS. SGLT2 inhibitors have demonstrated clear cardiovascular benefits in DKD which may be in part ascribed to the generation of a beneficial equilibrium between oxidant and antioxidant mechanisms.

Analysis Of The Influence Of Alcohol-Induced Stress On The Quantitative And Qualitative Composition Of Amino Acids Related To S-Adenosylmethionine And Glutathione Transformations

Studies of preparations that decrease oxidative stress and, as a consequence, that can prevent or reduce the development of alcoholic liver disease are relevant. A wide range of drugs, the bioprotective effect of which is studied, in its action is associated with natural antioxidant systems. Therefore, the study of the features of these systems is necessary for the effective development of bio protectors. The aim is to analyze changes in the quantitative and qualitative composition of amino acids involved in antioxidant mechanisms in the presence of alcohol-induced stress in rats. In the presence of alcohol-induced oxidative stress, there are changes in the quantitative and qualitative composition of amino acids (methionine, serine, taurine), which are involved in the mechanisms of antioxidant protection - cycles of S-adenosylmethionine and glutathione. A slight increase in methionine levels in the blood serum of animals of the experimental group and disruption of the recovery cycle of methionine under alcohol-induced oxidative stress are arguments for the ineffectiveness of S-adenosylmethionine as a bioprotective substance. The same decrease in the level of serine (by 15%) and taurine (by 13%), and analysis of literature data, may be indicate the "secondary" nature of glutathione as an antioxidant compared to taurine.

Crosstalk between Neuron and Glial Cells in Oxidative Injury and Neuroprotection

To counteract oxidative stress and associated brain diseases, antioxidant systems rescue neuronal cells from oxidative stress by neutralizing reactive oxygen species and preserving gene regulation. It is necessary to understand the communication and interactions between brain cells, including neurons, astrocytes and microglia, to understand oxidative stress and antioxidant mechanisms. Here, the role of glia in the protection of neurons against oxidative injury and glia–neuron crosstalk to maintain antioxidant defense mechanisms and brain protection are reviewed. The first part of this review focuses on the role of glia in the morphological and physiological changes required for brain homeostasis under oxidative stress and antioxidant defense mechanisms. The second part focuses on the essential crosstalk between neurons and glia for redox balance in the brain for protection against oxidative stress.

STUDY OF HEPATOPROTECTIVE ACTIVITY OF STINGLESS BEE PROPOLIS AGAINTS TOXICITY OF DRUGS

Objective: The aim of this study is to determine the effect of stingless bee propolis supplementation as a hepatoprotector on the prevention of DILI and the effect of healing and restoring nutrition for DILI patients due to drug induction. Methods: The literature review starts from problem identification, library data collection, reading, taking notes, analyzing, and processing the data obtained and then compiling it into a systematic review Results: The results of a literature study conducted show that propolis has a good hepatoprotective ability against drugs that cause DILI cases such as the anti-tuberculosis, antibiotic and antipyretic groups as indicated by the SGPT, SGOT, BT, GSH, and SOD values that are close to normal values. In addition, propolis supplementation can accelerate the healing and restoration of the nutritional status of DILI patients. All active compounds contained in propolis such as phytochemicals and lipopolysaccharides work to protect the liver from the toxic effects of DILI through antioxidant mechanisms. Conclusion: Overall, the data from this literature study show that the hepatoprotective activity of propolis has the potential to complement drug therapy to reduce hepatotoxic effects and can conclusively beneficial to accelerate the restoration of nutritional status for DILI patients.

Analysis of the oxidative stress inhibition potentials of Artemisia annua and its bioactive compounds through in vitro and in silico studies

Oxidative stress overwhelms the antioxidant mechanisms of living systems, with active involvement in the pathogenesis of several diseases. Natives of Gangnim in the Plateau State of Nigeria may be unknowingly endowed with some protective advantages against oxidative stress for their habitual consumption of Artemisia annua tea. The antioxidant activities of A. annua extracts were determined using in vitro methods and the inhibitory potentials of twenty-nine (29) bioactive compounds of the plant against oxidative stress target proteins were assessed through molecular docking analysis. These extracts showed significantly high activities in scavenging nitric oxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing ferric (Fe3+) to ferrous (Fe2+) iron. Virtually, none of the bioactive compounds binds to the active site of the antioxidant protein targets. Rather, 72.41, 93.10 and 75.86% of these compounds bind with high binding affinity to the activator binding sites of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) respectively. 7,8-dimethylalloxazine (-8.10 kcal/mol) ranked highest as a prospective inhibitor of xanthine oxidase (XOX). The antioxidant activity exhibited by the extracts of the locally cultivated A. annua and the molecular interactions of its bioactive compounds against the protein targets used predict that oxidative stress inhibition could be effectively achieved with these phytochemicals.

Effect of Astaxanthin on Anti-Inflammatory and Anti-Oxidative Effects of Astaxanthin Treatment for Atopic Dermatitis-induced Mice

Background: This study sought to determine whether the antioxidant effects of astaxanthin (AST) could have an anti-inflammatory effect to reduce inflammation caused by atopic dermatitis (AD).Methods: Using a mouse model of AD induced by phtalic acid (PA), the levels of inflammation, inflammatory agents, and evidence of antioxidant activity were examined in PA treated mice (n = 3), PA-AST treated mice (n = 3), and a control group of mice (n = 3). This included measurements of ear thickness, levels of mast cells, IgE, inflammatory cytokine, malondialdehyde (MDA), hydrogen peroxide, HO-1, and GPx-1.Results: AST treatment significantly prevented inflammation as measured by ear thickness (p < 0.05), mast cell count (p < 0.001), and IgE concentration in the blood (p < 0.001). Levels of TNF-α (p < 0.001), IL-1β (p < 0.001), IL-6 (p < 0.001), and MDA (p < 0.05) were also significantly lower. In addition, GSH levels increased significantly (p < 0.001), and the level of hydrogen peroxide significantly reduced (p < 0.01). The expression of HO-1, GPx-1 increased.Conclusion: In this small experimental study, AST acted on inflammatory mechanisms that induced AD, through anti-inflammatory and antioxidant mechanisms, and is a candidate of interest in the clinical treatment of AD.

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, free radicals are effectively eliminated by numerous antioxidant mechanisms. Oxidative stress occurs due to an imbalance between the production and elimination of free radicals under pathological conditions. Oxidative stress is also associated with ageing. The brain is prone to oxidative damage because of its high metabolic activity and high vulnerability to ischemic damage. Oxidative stress, thus, plays a major role in the pathophysiology of both acute and chronic pathologies in the brain, such as stroke, traumatic brain injury or neurodegenerative diseases. The goal of this article is to summarize the basic concepts of oxidative stress and its significance in brain pathologies, as well as to discuss treatment strategies for dealing with oxidative stress in stroke.

A Systematic Review and Meta-Analysis of the Effect of Statins on Glutathione Peroxidase, Superoxide Dismutase, and Catalase

Statins may exert protective effects against oxidative stress by upregulating specific antioxidant mechanisms. We conducted a systematic review and meta-analysis of the effect of statins on three key antioxidant enzymes: glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. The electronic databases PubMed, Web of Science, and Scopus were searched from inception to July 2021. The risk of bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklist and certainty of evidence was assessed using the GRADE framework. In 15 studies, reporting 17 treatment arms in 773 patients (mean age 53 years, 54% males), statins significantly increased the concentrations of both GPx (standardized mean difference, SMD = 0.80, 95% confidence interval, CI 0.13 to 1.46, p = 0.018; high certainty of evidence) and SOD (SMD = 1.54, 95% CI 0.71 to 2.36, p < 0.001; high certainty of evidence), but not catalase (SMD = −0.16, 95% CI −0.51 to 0.20, p = 0.394; very low certainty of evidence). The pooled SMD values were not altered in sensitivity analysis. There was no publication bias. In conclusion, statin treatment significantly increases the circulating concentrations of GPx and SOD, suggesting an antioxidant effect of these agents (PROSPERO registration number: CRD42021271589).

Transcriptome Profiles of Leaves and Roots of Goldenrain Tree (Koelreuteria paniculata Laxm.) in Response to Cadmium Stress

Cadmium (Cd) pollution is a widespread environmental problem. In this study, we explored the transcriptome and biochemical responses of goldenrain tree (Koelreuteria paniculata Laxm.) leaves and roots to Cd stress. Leaf and root growth decreased substantially under Cd stress (50 mg/L CdCl2), but leaf and root antioxidant mechanisms were significantly activated. In RNA-seq analysis, roots treated with 25 mg/L CdCl2 featured enriched GO terms in cellular components related to intracellular ribonucleoprotein complex, ribonucleoprotein complex, and macromolecular complex. In leaves under Cd stress, most differentially expressed genes were enriched in the cellular component terms intrinsic component of membrane and membrane part. Weighted gene co-expression network analysis and analysis of module–trait relations revealed candidate genes associated with superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and malondialdehyde (MDA). Ten transcription factors responded to Cd stress expression, including those in C2H2, MYB, WRKY, and bZIP families. Transcriptomic analysis of goldenrain tree revealed that Cd stress rapidly induced the intracellular ribonucleoprotein complex in the roots and the intrinsic component of membrane in the leaves. The results also indicate directions for further analyses of molecular mechanisms of Cd tolerance and accumulation in goldenrain tree.