Agil 2020 J Clin Med

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Agil A, Chayah M, Visiedo L, Navarro-Alarcon M, Rodríguez Ferrer JM, Tassi M, Reiter RJ, Fernández-Vázquez G (2020) Melatonin improves mitochondrial dynamics and function in the kidney of Zücker diabetic fatty rats. J Clin Med 9:E2916.

» PMID: 32927647 Open Access

Agil Ahmad, Chayah Meriem, Visiedo Lucia, Navarro-Alarcon Miguel, Rodriguez Ferrer Jose Manuel, Tassi Mohamed, Reiter Russel J, Fernandez-Vazquez Gumersindo (2020) J Clin Med

Abstract: Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.

Keywords: Drp1, Mfn2, Opa1, ZDF rats, Diabetes, Fission/fusion, Melatonin Mitochondrial function/dynamic, Nephropathy, Obesity Bioblast editor: Plangger M


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Pharmacology;toxicology  Pathology: Diabetes, Obesity 

Organism: Rat  Tissue;cell: Kidney  Preparation: Isolated mitochondria  Enzyme: Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

2020-09