Mitochondrial dysfunction at the early stage of cisplatin-induced acute renal failure in rats

Abstract

The present study was undertaken to clarify the pathogenesis of cisplatin-induced acute renal failure at the early stage. Male Sprague-Dawley rats were given an intravenous administration of 10 mg/kg cisplatin. 0.9% saline was infused into them at a rate of 2 ml/h for 3 h, starting with a 2-ml bolus injection before cisplatin administration. 3 h following cisplatin administration, no evident morphological abnormalities were found by both light and electron microscopy; there were also no significant changes in GFR. Thirty min after cisplatin injection, urine sodium and potassium excretion increased by 56% and 260% those of the control animals, respectively. Apparent renal mitochondrial respiration dysfunction was observed in cisplatintreated rats 3 h later; the state 4 respiration increased by 100% and state 3 respiration, respiratory control ratio and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone-uncoupled respiration decreased by 46%, 74% and 47% of the controls, respectively. The present data suggest that mitochondrial dysfunction may be a very early event in cisplatin-induced acute renal failure in rats.