Moslen M T, Reynolds E S
Res Commun Chem Pathol Pharmacol. 1985 Jan;47(1):59-72.
Administration of 200 mg 1,1-dichloroethylene (1,1-DCE)/kg to fasted male rats rapidly decreased liver cytosolic glutathione (GSH) S-transferase activities by half within 1 hr. This early decrease was not associated with increased serum activities of this soluble enzyme and is considered due to enzyme deactivation. The early decrease in enzyme activities was concomitant with a three-fourths depletion of cytosolic GSH and preceded changes in cytochrome P-450 and the onset of liver cytotoxicity, both of which occurred abruptly between 2 and 3 hr. Substantial changes in GSH S-transferase activities at 4 hr were produced only by severely hepatotoxic doses of 1,1-DCE. The early decrease in hepatic GSH S-transferase activities was selective for substrates dichloronitrobenzene, chlorodinitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)-propane with apparent sparing of activity towards ethacrynic acid. The rapid, selective and dose-dependent deactivation of the hepatic GSH S-transferases could be relevant to the catastrophic hepatotoxicity of 1,1-DCE.
给禁食的雄性大鼠腹腔注射200毫克/千克的1,1 - 二氯乙烯（1,1 - DCE），1小时内肝脏胞质谷胱甘肽（GSH）S - 转移酶活性迅速降低一半。这种早期降低与该可溶性酶的血清活性增加无关，被认为是由于酶失活所致。酶活性的早期降低与胞质GSH减少四分之三同时发生，并先于细胞色素P - 450的变化和肝脏细胞毒性的出现，这两者均在2至3小时之间突然发生。仅在1,1 - DCE具有严重肝毒性剂量时，4小时时GSH S - 转移酶活性才会发生显著变化。肝脏GSH S - 转移酶活性的早期降低对底物二氯硝基苯、氯二硝基苯和1,2 - 环氧 - 3 -（对硝基苯氧基）丙烷具有选择性，对依他尼酸的活性似乎未受影响。肝脏GSH S - 转移酶的快速、选择性和剂量依赖性失活可能与1,1 - DCE的灾难性肝毒性有关。
