EFFECT OF SIMVASTATIN IN GENTAMICIN INDUCED NEPHROTOXICITY IN ALBINO RATS

Gentamicin (GM) is an aminoglycosidal antibiotic widely used in treating severe gram-negative infections. However its limited uses due to renal dysfunction. The aim of the present work was to investigate the possible protective effect of the simvastatin, an anti-hypolipidemic drug on gentamicin induced nephrotoxicity. For this purpose, albino rats were selected and divided into four groups, each group comprised of six albino rats. Group 1 served as normal control received vehicle, Group 2 was injected with gentamicin (80 mg/kg/day) intraperitoneally, Group 3 administered with simvastatin alone (10 mg/kg/day) orally and the group 4 animals received gentamicin (80 mg/kg/day) intraperitoneally and simvastatin (10mg/kg/day) orally. All the test drugs were administered for 10 days. On10th day blood was collected and serum was separated for the estimation of blood urea nitrogen, serum creatinine, and protein contents. Then the rats were sacrificed and kidneys were removed for histopathological studies. Moreover, glutathione (GSH), and thiobarbituric acid relative substances (TBARS) levels activities were determined in renal tissues. The results showed are concomitant administration of simvastatin significantly reduced gentamicin induced elevated levels of serum creatinine, blood urea and urea nitrogen in albino rats. There was significant decrease in GSH levels and increase in TBARS levels, indicated that GMinduced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of simvastatin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.