ASSESSMENT THE EFFECT OF CAPTOPRIL, NIFEDIPINE AND THEIR COMBINATION ON GENTAMICIN INDUCED NEPHROTOXICITY IN RATS.

This study is aimed to evaluate the effect of captopril (an ACE inhibitor), nifedipine (calcium channel blocker) and their combination on gentamicin induced nephrotoxicity. Captopril in a dose of 25mg/kg, nifedipine(20mg/kg) and their combination were orally administered to male albino rats for 6 days before and for 7 days along with gentamicin injection(80 mg/kg, IP). At the end of the study, body and kidney weights were recorded. Serum creatinine, blood nitrogen urea, albumin, lactate dehydrogenase (LDH) sodium and calcium levels were measured. In addition renal lipid peroxidation represented by malondialdehyde (MDA) and renal reduced glutathione (GSH) were also estimated. Histopathological examination of the kidney was also performed. Results of the present study showed that gentamicin induced significant increase in kidney weight, serum creatinine, blood nitrogen urea, and LDH levels. On the other hand serum sodium levels were reduced. Renal MDA was elevated and reduced GSH was significantly decreased in kidney tissues. Histopathological examination showed renal damage indicated by severe hydropic degeneration or focal necrosis and mild interstitial lymphocytic aggregations. Captopril reduced serum creatinine and increased kidney GSH content. It also reduced histopathological changes. Nifedipine decreased serum creatinine, urea and renal MDA levels. It increased serum sodium and calcium levels and renal GSH content. Histopathological examination showed that nifedipine modulated renal damage induced by gentamicin. However, captopril and nifedipine combination increased serum urea, creatinine and calcium levels and renal MDA levels. It reduced serum sodium levels. Histopathpathological examination demonstrated severe damage manifested by diffuse coagulative necrosis in all segments of the nephron in both cortex and medulla. In conclusion both captopril and nifedipine when used alone exerted a protective effect against gentamicin-induced nephrotoxicity .Nifedipine was better than captopril in this regard. However, their combination has a deleterious effect and exacerbated gentamicin- induced nephrotoxicity. The underlying mechanism(s) of this negative interaction needs further investigation.