Kornbrust D J, Bus J S
Toxicol Appl Pharmacol. 1984 Mar 15;72(3):388-99. doi: 10.1016/0041-008x(84)90115-7.
Inhalation of methyl chloride (CH3Cl) by male B6C3F1 mice resulted in a concentration-dependent depletion of glutathione (GSH) in liver, kidney, and brain. Exposure for 6 hr to 100 ppm CH3Cl decreased the concentration of GSH in mouse liver by 45%, while exposure to 2500 ppm for 6 hr lowered liver GSH to approximately 2% of control levels. For those exposures which decreased liver GSH to less than 20% of control levels, the extent of liver GSH depletion was closely correlated with the capacity of a 9000g supernatant fraction from the liver to undergo lipid peroxidation in vitro. GSH was depleted to a lesser extent in mouse brain and kidney, compared to liver, and no relationship to peroxidation was observed for single exposures to CH3Cl. A dose-dependent decrease in liver GSH was also produced by diethyl maleate, although a nearly lethal amount (2 ml/kg) was required to lower liver GSH to less than 10% of control levels. Under these conditions the amount of lipid peroxidation was 3.5-fold less than in mice exposed to 2000 ppm CH3Cl. Exposure of rats to 2000 ppm CH3Cl reduced liver GSH to 20% of control levels, compared to 4.5% in mice similarly exposed, and under these exposure conditions the amount of lipid peroxidation measured in vitro was 40-fold greater in mouse liver than in rat liver. During exposure of mice to 2500 ppm CH3Cl, ethane expiration increased to an extent comparable to that produced by administration of 2 ml/kg of CCl4. These findings suggest that GSH depletion in liver may be an important component of CH3Cl-induced hepatotoxicity.
雄性B6C3F1小鼠吸入氯甲烷（CH3Cl）会导致肝脏、肾脏和大脑中的谷胱甘肽（GSH）浓度依赖性降低。暴露于100 ppm CH3Cl 6小时会使小鼠肝脏中的GSH浓度降低45%，而暴露于2500 ppm 6小时会使肝脏GSH降至对照水平的约2%。对于那些使肝脏GSH降至对照水平不到20%的暴露情况，肝脏GSH的消耗程度与肝脏9000g上清液部分在体外进行脂质过氧化的能力密切相关。与肝脏相比，小鼠大脑和肾脏中的GSH消耗程度较小，单次暴露于CH3Cl时未观察到与过氧化的关系。马来酸二乙酯也会导致肝脏GSH剂量依赖性降低，尽管需要接近致死量（2 ml/kg）才能使肝脏GSH降至对照水平的不到10%。在这些条件下，脂质过氧化量比暴露于2000 ppm CH3Cl的小鼠少3.5倍。与同样暴露的小鼠中4.5%相比，大鼠暴露于2000 ppm CH3Cl会使肝脏GSH降至对照水平的20%，在这些暴露条件下，体外测量的小鼠肝脏脂质过氧化量比大鼠肝脏大40倍。在小鼠暴露于2500 ppm CH3Cl期间，乙烷呼出量增加到与给予2 ml/kg CCl4产生的程度相当。这些发现表明，肝脏中的GSH消耗可能是CH3Cl诱导的肝毒性的重要组成部分。
