Abstract

S. M. Poormoosavi, M. A. Behmanesh and H Najafzadeh*

Drug-induced nephrotoxicity is an important cause of renal failure. Aminoglycoside antibiotics, such as gentamicin can produce nephrotoxicity, due to in part to an imbalance of pro and anti-oxidants (oxidative stress). Cytochrome P 450 is one enzyme that involved in acute renal failure. Inhibition of this enzyme may decrease drug-induced nephrotoxicity. The aim of present study was evaluating the effect of cimetidine on gentamicin-losartan nephrotoxicity in rats. A control group (saline, group 1, n = 6) was compared with rats administrated gentamaicin by intrapritoneal injection, at dose rate of 80 mg/kg, once daily for 7 days (group 2, 3 and 4). The effect of losartan (group 3) and losartan and cimetidine in combination (group 4) were compared on gentamaicin-induced nephrotoxicity. Losartan alone (group 5) and losartan with cimetidine (group 6) were used for evaluation effect of these drugs in absence of gentamicin. Renal function was assessed using serum biochemical markers including creatinine, blood urea nitrogen (BUN), sodium and potassium. Serum creatinine concentration was increased significantly in group 2 compared with group 1. Serum creatinine concentrations were significantly elevated in groups 3 than in group 2 (p = 0.001). Serum creatinine concentration was significantly decreased in groups 4 than in group 3 (p = 0.001) . Serum creatinine concentration in group 5 and 6 was similar group 1. Serum BUN concentrations were significantly elevated in groups 3 than in group 2 (p = 0.001). The cimetidine prevented BUN elevation in group 4 with comparison to group 3 but serum BUN in this group was significantly more than groups 1 and 2. Serum sodium level was significantly decreased in group 3. Serum potassium level significantly increased in group 3 and 4. Losartan severely increased gentamicin-induced nephrotoxicity. Cimetidine appears to have protective effect on gentamicin-losartan-induced nephrotoxicity in rats.