Effect of spironolactone on cisplatin-induced nephrotoxicity in rabbits

The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day(-1)), oral doses of spironolactone (20.0 mg kg day(-1)) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P <0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four- and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spironolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spironolactone significantly (P <0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit.