Comparison between metformin and intermittent fasting for renoprotective effects through mitophagy modulation in a rat cisplatin-induced acute kidney injury model

The current study investigated the effects of metformin versus intermittent fasting as modulators of mitophagy in cisplatin-induced acute renal injury in rats. Twenty-four adult male rats were divided into four groups: control, cisplatin, metformin-treated, and intermittent fasting groups. Cisplatin (8 mg/kg, intraperitoneal) was administered once on day eight, while metformin (200 mg/kg) was given orally for 12 days. Renal function parameters including serum creatinine, blood urea nitrogen (BUN), fractional excretion of sodium (FENa), and serum sodium and potassium levels were measured, along with urinary neutrophil gelatinase associated lipocalin (NGAL) and renal oxidative stress markers malondialdehyde and superoxide dismutase (MDA and SOD). Mitophagy was assessed by immunohistochemical evaluation of Microtubule-Associated Protein 1 Light Chain and Nucleoporin p62 (LC3 and p62) expression, measurement of PTEN-induced kinase 1(PINK1) levels, and Parkin gene expression, along with histopathological examination of renal tissues. Cisplatin administration significantly impaired kidney function, increased oxidative stress and p62 expression, and reduced SOD, LC3, PINK1, and Parkin gene expression, accompanied by marked histopathological renal damage. Treatment with metformin or intermittent fasting significantly improved renal function tests, reduced oxidative stress and p62 levels, and restored LC3, PINK1, and Parkin expression, with corresponding improvement in renal histopathology. These findings suggest that metformin and intermittent fasting exert protective effects against cisplatin-induced acute kidney injury, potentially through modulation of oxidative stress and mitophagy pathways.