Ameliorative potential of gemfibrozil and silymarin onexperimentally induced nephrotoxicity in rats

Abstract

Introduction: Acute nephrotoxicity is a frequent complication of critical illness especially in the inpa-tient setting. Cisplatin is one of the most active anticancer drugs. Nephrotoxicity is the most commonside effect associated with cisplatin treatment. Silymarin is widely used for hepatic disorders due to itsantioxidant and anti-inflammatory properties. Gemfibrozil, a hypolipidemic drug, has also antioxidant andanti-inflammatory properties.

Objective: To detect the effect of gemfibrozil and silymarin either alone or in combination on cisplatin-induced nephrotoxicity in rats.

Subjects and methods: Fifty albino rats were divided into 5 equal groups: Control untreated group,cisplatin treated group, gemfibrozil + cisplatin treated group, silymarin + cisplatin treated group, gemfi-brozil + silymarin + cisplatin treated group. Blood urea, serum creatinine, creatinine clearance, urinaryN-acetyl beta-d-glucosaminidase, urinary protein, tissue superoxide dismutase, malondialdehyde, reducedglutathione, tumour necrosis factor alpha and mitochondrial complex I activity were determined. Kidneyswere excised for histopathological examination.

Results: Gemfibrozil and/or silymarin efficiently attenuated cisplatin-induced nephrotoxicity evidenced bysignificant decrease in blood urea, serum creatinine, urinary N-acetyl beta-d-glucosaminidase, urinary pro-tein, tissue malondialdehyde and tissue tumour necrosis factor alpha with significant increase in creatinineclearance, tissue reduced glutathione, tissue superoxide dismutase and mitochondrial complex I activitysimultaneous with reduction of the necrotic damage and progressively increasing apoptotic index assessedby renal histopathological examination compared to the cisplatin treated group.

Keywords: Gemfibrozil; Silymarin; Nephrotoxicity; Rats; Cisplatin