RESUMEN
Cyclosporin-A [CsA] has markedly improved the results of transplantation and its use is extended to include autoimmune and primary renal diseases. However, the major limitation of its use is its nephrotoxicity. P-glycoprotein [P-gp] is a transmembrane efflux pump for hydrophobic, potentially toxic compounds, including CsA. CsA has been shown to increase P-gp expression in tubular and endothelial cells. Aim of Work: The aim of the present study was to elucidate the protective effect of the calcium channel blockers lacidipine and verapamil against CsA-induced nephrotoxicity and the relation of this protective effect to P-gp expression in rat kidney. This study included 7 groups, each containing 7 rats: oral saline group. intraperitoneal [IP] saline group, CsA [25 mg/kg/] group: rats received CsA IP for 14 days, lacidipine [1 mg/kg/d] group: rats received lacidipine orally for 17 days, concomitant lacidipine and CsA group: rats received lacidipine for 3 days and concomitant with CsA for another 14 days, yerapamil [0.1 mg/kg/d] group: rats received erapamil i.p for 17 days and concomitant verapamil and CsA group: rats received verapamil for 3 days and concomitant with CsA for another 14 days Serum creatinine, histopathological and immunostaining for P-gp for rat kidneys were done for all rats. This study revealed that CsA significantly raised serum creatinine, produced vacuolization and necrosis in tubular cells and increased P-gp expression. Kidneys treated with lacidipine alone revealed no significant changes biochemically and histologically. When lacidipine was given with CsA, it significantly protected the kidneys against CsA-induced nephrotoxicity and increased expression of P-gp in kidneys. Verapamil alone caused mild nephrotoxicity in the form of vacuolization and increased serum creatinine level. It also inhibited P-gp expression in rat kidneys. Verapamil given with CsA significantly ameliorated CsA nephrotoxicity and decreased P-gp expression. lacidipine had protective effect against CsA nephrotoxicity more than verapamil. Hemodynamic effect is the main effect and moreover, lacidipine may protect via P-gp over- expression