Probucol protects against gentamicin-induced nephrotoxicity in rats

Abstract

Objective: To investigate the effect of probucol on gentamicin-induced nephrotoxicity in rats. Methods: Male Wistar rats were divided into 4 groups; normal saline, gentamicin 80 mg/kg, i.p., intraperitoneally for 8 days, probucol 10 mg/kg, p.o., for 11 days, probucol 3 days and concurrently with gentamicin for 8 days. Blood urea, serum creatinine, plasma malondialdehyde (MDA), creatinine clearance, urinary sodium, potassium and microscopic examination of kidney were performed after the treatment. Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Blood urea and serum creatinine were increased by 963% and 462% respectively with gentamicin compared to saline-treated animals. Co-administration of probucol with gentamicin decreased the rise in blood urea and serum creatinine. Creatinine clearance (Ccr) was significantly decreased by 89% with gentamicin compared to control. Treatment with probucol improved Ccr by 24% compared to gentamicin treated group. There was a 177% rise in lipid peroxidation products (MDA) with gentamicin than control, which was significantly reduced by 44% with probucol. Study of renal morphology by light microscope showed epithelial loss with intense granular degeneration involving >50% renal cortex in gentamicin treated rats, whereas in probucol plus gentamicin treated rat revealed insignificant changes in tubular epithelium. Conclusion: Our data suggest that supplementation of probucol may be useful in reducing gentamicin nephrotoxicity in rats.