1,1-Dichloroethylene hepatotoxicity. Time course of GSH changes and biochemical aberrations.
Exposure of fasted rats to 200 ppm 1,1-dichloroethylene (1,1-DCE) for 1-4 hours resulted in striking aberrations in hepatic Na, K, Ca, and GSH levels which preceded and/or accompanied catastrophic histologic alterations of the liver. Na levels began to rise during the first hour, and preceded the morphologically apparent injury. Ca levels increased markedly and K levels declined between the second and fourth hour of exposure, and accompanied the catastrophic morphologic alterations. GSH levels were rapidly depleted but began to recover before the end of the exposure to 1,1-DCE. Functions of components of the mixed-function oxidase system of the liver endoplasmic reticulum were not appreciably affected early in the course of 1,1-DCE exposure; but after injury became massive, cytochrome P-450 and oxidative N-demethylase were deactivated. Thus effects on the functional components of the endoplasmic reticulum mixed-function oxidase system do not appear to be primary events in 1,1-DCE cytotoxicity. In contrast, there were progressive declines in mitochondrial K and marked imbalances in mitochondrial Na, Zn, and Mg preceding the massive influx of Ca into the cell, indicating that mitochondria are involved early in he evolution of injurious molecular events elicited by this potent hepatotoxin.
D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008930:Mitochondria, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D006899:Mixed Function Oxygenases; D007064:L-Iditol 2-Dehydrogenase; D005978:Glutathione