Effect of methanol or modifications of the hepatic glutathione concentration on the metabolism of dichloromethane to carbon monoxide in rats.
1. 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.
Pankow
D
D
Institute of Industrial Toxicology, Martin Luther University, Halle (Saale), Germany.
Jagielki
S
S
D000818:Animals; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002263:Carboxyhemoglobin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000432:Methanol / Q000494:pharmacology / Q000633:toxicity*; D008752:Methylene Chloride / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D008752:Methylene Chloride; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D005978:Glutathione; D000432:Methanol