The effect of age on salicylate-induced nephrotoxicity in male rats.
The administration of 500 mg/kg sodium [14C]salicylate to 3- and 12-month-old male rats produced proximal tubular necrosis in the older animals but only mild nonspecific cellular changes in the younger group. The onset of renal damage was similar for both 3- and 12-month-old rats but recovery time was prolonged in the older rats. Covalent binding of salicylate equivalents was present in renal cortices from all rats and was largely confined to the mitochondrial fraction; however, older rats displayed five times more binding to this organelle than younger rats. Also the mitochondrial pathway for salicylurate synthesis was significantly inhibited in the older animals. These results demonstrate the existence of an age-dependent susceptibility to salicylate nephrotoxicity and suggest that mitochondrial injury may play an important role in the development of salicylate-induced proximal tubular necrosis.