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.

Keywords:

• Bcl-2
• berberine
• gentamicin
• KIM-1
• nephrotoxicity
• NF-KB
• NGAL

Acknowledgements

The authors would like to acknowledge Dr S. S. Kadam, Vice-Chancellor and Dr K. R. Mahadik, Principal, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India, for providing necessary facilities to carry out the study. The authors would also like to acknowledge Dr Pralhad Wangikar, CEO-PRADO, Pune, India, for providing necessary facilities to carry out histological analysis. The authors would also like to acknowledge Invaluesys Research Group to carry out statistical analysis of the study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.