Devalia J L, Ogilvie R C, McLean A E
Biochem Pharmacol. 1982 Dec 1;31(23):3745-9. doi: 10.1016/0006-2952(82)90287-8.
Paracetamol metabolism and toxicity were studied in isolated rat hepatocytes. Cell damage, due to paracetamol, was shown to be dose dependent and was worse in cells from animals pre-treated with phenobarbitone. Exposure to 10 mM paracetamol for 1 hr caused a loss of intracellular reduced glutathione (GSH) and a later progressive leakage of isocitrate dehydrogenase (ICD). Treatment with (+)catechin, 3-O-methyl(+)catechin and promethazine reduced or prevented the paracetamol-induced ICD leakage. Similarly, studies on covalent binding of paracetamol showed that 3-O-methyl(+)catechin, which "protected" the cells, did so without affecting the amount of material bound covalently to cellular protein. Incubation in tissue culture for 24 hr, after prior treatment with paracetamol +/- the protective agent, showed that the protected cells remained viable and attached to tissue culture plates much better than did the "unprotected" cells. These results suggest that the protective effect is much more than just a temporarily delayed cell death. GSH loss and covalent binding of paracetamol metabolites to cell protein are not sufficient causes of cell death, although they may act as starting points in the chain of events leading to cell death.
在分离的大鼠肝细胞中研究了对乙酰氨基酚的代谢和毒性。结果表明，对乙酰氨基酚引起的细胞损伤具有剂量依赖性，并且在用苯巴比妥预处理的动物的细胞中更严重。将细胞暴露于10 mM对乙酰氨基酚1小时会导致细胞内还原型谷胱甘肽（GSH）损失，随后异柠檬酸脱氢酶（ICD）逐渐泄漏。用（+）儿茶素、3-O-甲基（+）儿茶素和异丙嗪处理可减少或防止对乙酰氨基酚诱导的ICD泄漏。同样，关于对乙酰氨基酚共价结合的研究表明，“保护”细胞的3-O-甲基（+）儿茶素在不影响与细胞蛋白共价结合的物质数量的情况下起到了保护作用。在用对乙酰氨基酚 +/- 保护剂预处理后，在组织培养中孵育24小时，结果显示受保护的细胞比“未受保护”的细胞保持活力并更好地附着在组织培养板上。这些结果表明，保护作用不仅仅是暂时延迟细胞死亡。GSH损失和对乙酰氨基酚代谢物与细胞蛋白的共价结合虽然可能是导致细胞死亡的一系列事件的起始点，但并不是细胞死亡的充分原因。
