甲醇或肝脏谷胱甘肽浓度的改变对大鼠体内二氯甲烷代谢生成一氧化碳的影响。

Effect of methanol or modifications of the hepatic glutathione concentration on the metabolism of dichloromethane to carbon monoxide in rats.

Pankow D, Jagielki S

Institute of Industrial Toxicology, Martin Luther University, Halle (Saale), Germany.

Hum Exp Toxicol. 1993 May;12(3):227-31. doi: 10.1177/096032719301200305.

Abstract

The metabolism of dichloromethane (DCM) to carbon monoxide as measured by the carboxyhaemoglobin (COHb) level in the blood is stimulated by pretreatment with methanol (MET). After simultaneous administration of both DCM, 6.2 mmol kg-1 p.o., and MET, > 148 mmol kg-1 p.o., the COHb formation is inhibited. 2. MET ingestion results in a transient decrease of the glutathione (GSH) content of the liver. In rats treated with GSH-depleting chemicals such as diethylmaleate (DEM), phorone (PHO), or buthionine sulphoximine (BSO) there were no enhancements of the carboxyhaemoglobinaemia caused by DCM. The COHb formation was not influenced by an increase of the hepatic GSH concentration due to repeated administration of butylated hydroxyanisole (BHA). 3. It is concluded that cytochrome P450 IIE1 (CYP 2E1) is responsible for the metabolic interaction of both DCM and MET, and MET may be an inducer of CYP 2E1. The two pathways of DCM, the oxidative via CYP 2E1 and the metabolism via GSH/GSH-S-transferase seem to be independent.

摘要

通过血液中碳氧血红蛋白（COHb）水平测定，二氯甲烷（DCM）代谢生成一氧化碳的过程会受到甲醇（MET）预处理的刺激。口服给予DCM 6.2 mmol/kg和MET > 148 mmol/kg后，COHb的形成受到抑制。2. 摄入MET会导致肝脏中谷胱甘肽（GSH）含量短暂下降。在用马来酸二乙酯（DEM）、佛尔酮（PHO）或丁硫氨酸亚砜胺（BSO）等耗竭GSH的化学物质处理的大鼠中，DCM引起的碳氧血红蛋白血症没有增强。由于反复给予丁基羟基茴香醚（BHA）导致肝脏GSH浓度升高，COHb的形成未受影响。3. 得出的结论是，细胞色素P450 IIE1（CYP 2E1）负责DCM和MET的代谢相互作用，且MET可能是CYP 2E1的诱导剂。DCM的两条代谢途径，即通过CYP 2E1的氧化途径和通过GSH/谷胱甘肽S-转移酶的代谢途径似乎是相互独立的。