Järvisalo J, Savolainen H, Elovaara E, Vainio H
Acta Pharmacol Toxicol (Copenh). 1977 Feb;40(2):329-36. doi: 10.1111/j.1600-0773.1977.tb02085.x.
The binding of 35S and 14C labelled CS2 to liver microsomes was studied in control and phenobarbitone pretreated rats 3 and 6 hrs after an intraperitoneal injection. The level of hepatic cytochrome P-450, the activities of epoxide hydratase and UDP-glucuronosyltransferase were analyzed in the same animals. The binding of the sulphur label was considerably higher than that of carbon 3 hrs after the injection, the difference being less evident at 6 hrs.T he measurable P-450 declined after the CS2 injection. It was approximately 40% in the phenobarbitone pretreated rats and 60% in control rats of the values of animals which were not treated with CS2. CS2 did not affect microsomal epoxide hydratase activity, while it increased the measurable activity of UDP-glucuronosyltransferase. The increase was evident 3 hrs after the injection of CS2 in the phenobarbitone pretreated rats. It could also be detected in the control animals 6 hrs after the injection. The present data suggest that the change in the measureble P-450 results from the binding of the metabolite(s) of CS2 to the cytochrome, and its subsequent degradation. The increase in measurable UDP-glycuronosyltransferase activity results probably from the activated perturbation of the structure of microsomal membrane by the metabolites of CS2 in vivo.
在腹腔注射3小时和6小时后，研究了35S和14C标记的二硫化碳（CS2）与对照大鼠和苯巴比妥预处理大鼠肝脏微粒体的结合情况。对同一批动物分析了肝细胞色素P - 450水平、环氧化物水解酶和UDP - 葡萄糖醛酸基转移酶的活性。注射后3小时，硫标记的结合量明显高于碳标记，6小时时差异不那么明显。注射CS2后可测量的P - 450下降。在未用CS2处理的动物中，苯巴比妥预处理大鼠的P - 450约为其值的40%，对照大鼠为60%。CS2不影响微粒体环氧化物水解酶活性，但增加了可测量的UDP - 葡萄糖醛酸基转移酶活性。在苯巴比妥预处理大鼠中，注射CS2后3小时活性增加明显。在对照动物中，注射后6小时也可检测到。目前的数据表明，可测量的P - 450变化是由于CS2代谢物与细胞色素结合及其随后的降解所致。可测量的UDP - 葡萄糖醛酸基转移酶活性增加可能是由于CS2代谢物在体内对微粒体膜结构的激活扰动所致。
