Raheja K L, Linscheer W G, Cho C, Coulson R
J Toxicol Environ Health. 1985;15(3-4):477-84. doi: 10.1080/15287398509530674.
The protective effect of 16, 16-dimethylprostaglandin E2 (dm-PGE2) against acetaminophen-induced hepatotoxicity was determined in the rat. The dm-PGE2 was administered at two dose levels both before and after acetaminophen administration. The hepatotoxicity was evaluated by a rise in serum transaminases 24 h after acetaminophen administration and by histological examination of liver preparations. The urinary acetaminophen and its metabolites were determined by high-pressure liquid chromatography. The results suggest that exogenous dm-PGE2 administration had a modest protection against acetaminophen-induced hepatotoxicity, in contrast to its well established cytoprotective effect against many noxious agents in the gastrointestinal tract. Prostaglandin treatment had little effect on acetaminophen metabolites excretion in the urine, suggesting that it did not affect the cytochrome P-450-dependent mixed-function oxidase drug-metabolizing enzyme system. The livers from dm-PGE2-acetaminophen-treated rats showed less advanced necrosis compared to those from saline-acetaminophen-treated rats. Whereas only 2 of 13 rats died in the prostaglandin-treated group, 4 of 13 rats died in the saline-treated group.
在大鼠中测定了16,16 - 二甲基前列腺素E2（dm - PGE2）对乙酰氨基酚诱导的肝毒性的保护作用。在给予乙酰氨基酚之前和之后，以两种剂量水平给予dm - PGE2。通过乙酰氨基酚给药24小时后血清转氨酶的升高以及肝脏制剂的组织学检查来评估肝毒性。通过高压液相色谱法测定尿中乙酰氨基酚及其代谢产物。结果表明，与dm - PGE2对胃肠道中许多有害剂具有的明确细胞保护作用相反，外源性给予dm - PGE2对乙酰氨基酚诱导的肝毒性具有适度的保护作用。前列腺素治疗对尿中乙酰氨基酚代谢产物的排泄几乎没有影响，表明它不影响细胞色素P - 450依赖性混合功能氧化酶药物代谢酶系统。与盐水 - 乙酰氨基酚处理的大鼠相比，dm - PGE2 - 乙酰氨基酚处理的大鼠肝脏显示出不太严重的坏死。前列腺素治疗组13只大鼠中只有2只死亡，而盐水处理组13只大鼠中有4只死亡。
