Glutathione depletion by methyl chloride and association with lipid peroxidation in mice and rats.
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.
D000818:Animals; D001273:Atmosphere Exposure Chambers; D002251:Carbon Tetrachloride / Q000633:toxicity; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000633:toxicity; D008737:Methyl Chloride / Q000633:toxicity*; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014018:Tissue Distribution
D008054:Lipid Peroxides; D008298:Maleates; D013438:Sulfhydryl Compounds; D008737:Methyl Chloride; D002251:Carbon Tetrachloride; C014476:diethyl maleate; D005978:Glutathione