Nephrotoxic effect of Atractyloside in rats

1. In male albino rats Atractyloside (50 mg/kg i.p.), well-known as inhibitor of oxidative phosphorylation, produces a tubular nephrosis 180 min after its administration. The nephrosis is characterized by a deep lesion in the cells of distal portion of proximal convoluted tubule and is accompanied by an increase of water excrection and by proteinuria, glicosuria, ketonuria, and kaliuria. The glomerulus appears intact; this is confirmed by the creatiniue and urea tests. The renal alteration subsides after 2 days of its onset. Similar effects are observed in mice but not in guinea pigs and rabbits. 2. Carboxyatractyloside (2 mg/kg i.p.), an analogue of atractyloside with a second carboxylic group in position 4, more active inhibitor of oxidative phosphorylation and more toxic, is devoid of any effect on rat kidney. 3. No functional or morphological alterations are observed in liver and heart of rats injected with these drugs. 4. The oxidative phosphorylation in homogenates of kidney and liver of rats pretreated with these compounds is inhibited to different extents. The possible relationship between nephrotoxic effect of atractyloside and the inhibition of oxidative phosphorylation is discussed. © 1974 Springer-Verlag.