Möller-Hartmann W, Siegers C P
Institute of Toxicology, Medical University of Lübeck, FRG.
J Appl Toxicol. 1991 Apr;11(2):141-6. doi: 10.1002/jat.2550110213.
Besides hepatotoxicity, paracetamol may exert nephrotoxic effects in experimental animals and patients. The present study in rats shows that antidotes known to protect against hepatotoxicity, such as methionine or N-acetylcysteine, are not effective in preventing paracetamol-induced kidney damage. Only diethyldithiocarbamate, an inhibitor of microsomal monooxygenases, provided complete protection against both hepato- and nephrotoxicity. While a marked depletion of glutathione was observed in the liver, no such effect was seen in the kidney. These data suggest that the mechanism of paracetamol nephrotoxicity seems to be quite different from that responsible for the hepatotoxicity. The hypothesis that a C-S-lyase-mediated final metabolism of paracetamol-S conjugates in the kidney might be responsible for nephrotoxicity needs support by further experimental investigations.
除肝毒性外，对乙酰氨基酚在实验动物和患者中可能产生肾毒性作用。目前对大鼠的研究表明，已知的可预防肝毒性的解毒剂，如蛋氨酸或N - 乙酰半胱氨酸，在预防对乙酰氨基酚诱导的肾损伤方面无效。只有微粒体单加氧酶抑制剂二乙基二硫代氨基甲酸盐能完全预防肝毒性和肾毒性。虽然在肝脏中观察到谷胱甘肽显著耗竭，但在肾脏中未观察到这种效应。这些数据表明，对乙酰氨基酚肾毒性的机制似乎与肝毒性的机制有很大不同。对乙酰氨基酚 - S共轭物在肾脏中由C - S裂解酶介导的最终代谢可能是肾毒性的原因这一假说需要进一步的实验研究来支持。
