Kyle M E, Kocsis J J
Toxicol Appl Pharmacol. 1985 Nov;81(2):337-47. doi: 10.1016/0041-008x(85)90171-1.
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.
给3个月和12个月大的雄性大鼠注射500毫克/千克的[14C]水杨酸钠后，老年动物出现了近端肾小管坏死，而年轻组仅出现了轻微的非特异性细胞变化。3个月和12个月大的大鼠肾损伤的发作情况相似，但老年大鼠的恢复时间延长。水杨酸盐等效物的共价结合存在于所有大鼠的肾皮质中，并且主要局限于线粒体部分；然而，老年大鼠与该细胞器的结合比年轻大鼠多五倍。此外，老年动物中水杨尿酸合成的线粒体途径受到显著抑制。这些结果证明了对水杨酸盐肾毒性存在年龄依赖性易感性，并表明线粒体损伤可能在水杨酸盐诱导的近端肾小管坏死的发展中起重要作用。
