5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense

Wijerathne, Charith Ub; Auyeung, Kathy Ka-Wai; Siow, Yaw L.; Karmin, O

doi:10.3390/antiox11061046

Cited by 10 publications

(3 citation statements)

References 58 publications

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“…Firstly, folate may have beneficial effects on physical function through its antioxidant effect [ 41 , 42 ]. Several studies have shown that folate or folic acid supplementation may attenuate oxidative stress by improving biomarkers in the antioxidative defense system, such as increased serum total antioxidant capacity and glutathione (GSH) concentration [ 13 , 43 , 44 , 45 , 46 ]. Studies have found that oxidative stress is an independent predictor of functional disability [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Zhang

et al. 2023

Antioxidants

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Folate may have beneficial effects on physical function through its antioxidant effect. Thus, we investigated the associations between serum folate and functional disability in older adults. Data from the National Health and Nutrition Examination Survey 2011–2018 were used. Serum folate included 5-methyltetrahydrofolate and total folate. Five domains of functional disability, including lower extremity mobility (LEM), instrumental activities of daily living (IADL), activities of daily living (ADL), leisure and social activities (LSA), and general physical activities (GPA), were self-reported. Multivariable-adjusted logistic regression models and restricted cubic splines were employed. 5-Methyltetrahydrofolate was inversely associated with IADL and GPA disability, and the multivariate-adjusted ORs (95% CIs) in the highest versus lowest quartiles were 0.65 (0.46–0.91) and 0.70 (0.50–0.96), respectively. The total folate was also inversely associated with IADL (OR quartile 4vs1 = 0.65, 95% CI: 0.46–0.90) and GPA (OR quartile 3vs1 = 0.66, 95% CI: 0.44–0.99) disability. The dose–response relationships showed a gradual decrease in the risk of IADL and GPA disability as serum folate increased. In the sex, age, BMI, and alcohol consumption subgroup analyses, we saw that the associations were primarily found in females, under 80 years old, normal weight, and non-drinkers. Sensitivity analyses further confirmed the robustness of our results. Our results indicated that serum folate concentrations were negatively associated with IADL and GPA disability, especially in females. In other subgroup analyses, we discovered that these negative associations were primarily prevalent in participants under 80 years old, normal weight, and non-drinkers.

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Section: Discussionmentioning

confidence: 99%

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Zhang

et al. 2023

Antioxidants

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“…The use of 5-MTHF in several diseases has been studied in animal models. It has been shown that 5-MTHF administered intravenously in rats with acute kidney injury reduced oxidative stress by increasing glutathione concentrations and reducing renal lipid peroxidation [113]. Rats with developed aortic atherosclerosis treated with 5-MTHF showed a decrease in homocysteine levels, an improvement in the serum lipid profile, an increase in the expression of NO and NOS, an enhancement of the antioxidant properties of GSH activity and a decrease in the expression of inflammatory factors: TNF-α, IL-6, IL -1β and endothelial cell damage factors: ET-1 and sICAM-1.…”

Section: Folic Acid Versus 5-mthf In Cad Therapymentioning

confidence: 99%

The Significance of Genetically Determined Methylation and Folate Metabolism Disorders in the Pathogenesis of Coronary Artery Disease: A Target for New Therapies?

Pietruszyńska-Reszetarska,

Pietruszyński,

Irzmański

2024

Preprint

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Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

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“…Tumor necrosis factor alpha (TNF-α) is a conventional marker of tissue inflammation [ 6 ]. Important indicators of oxidative stress are the extracellular antioxidant enzyme glutathione peroxidase 3 (GPx3), the cellular antioxidant enzyme heme oxygenase 1 (HO-1), and its transcriptional regulator nuclear factor erythroid 2-related factor 2 (NRF2) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice

Révész,

Kaucsár,

Godó

et al. 2024

IJMS

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Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia–reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR.

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5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense

Cited by 10 publications

References 58 publications

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

The Significance of Genetically Determined Methylation and Folate Metabolism Disorders in the Pathogenesis of Coronary Artery Disease: A Target for New Therapies?

Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice

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