Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

Abstract

Background: Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms. Material and methods: The rats were divided into various group, namely normal, GM-control, GM + BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney. Results: GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration. Conclusion: Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.