Trichloroethylene-induced deactivation of cytochrome P-450 and loss of liver glutathione in vivo.
Liver microsomal enzyme activities and glutathione (GSH) contents of fasted male rats pretreated with phenobarbital (PBT) or vehicle controls were measured during and after exposure to trichloroethylene (TRI) (1% x 2 hr). TRI caused morphologic liver injury only in the pbt animals. Cytochrome P-450 and b5 contents were diminished by the end of the first hr of TRI exposure and NADH-cytochrome c reduction increased three-fold by eight hr in the PBT animals. The only change in vehicle animals exposed to TRI was a decrease in NADPH-cytochrome c reductase activity by eight hr. Hepatic GSH contents of vehicle animals, constant during TRI exposure, rose with time. In contrast, in PBT animals, hepatic GSH contents decreased during TRI exposure and then rebounded. Decreases in GSH were most profound in the microsomal fraction. When fed animals with approximately two-fold higher hepatic GSH levels than fasted animals were exposed to TRI, they had shorter anesthesia recovery times and less liver injury, although excreting similar or slightly more trichlorinated metabolite into their urine in 24 hr than their fasted counterparts. We suggest that the hepatoxic effects of trichloroethylene are caused by inadequate detoxification of its reactive intermediates.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003579:Cytochrome Reductases / Q000378:metabolism; D003864:Depression, Chemical; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014241:Trichloroethylene / Q000494:pharmacology* / Q000652:urine
D014241:Trichloroethylene; D003577:Cytochrome P-450 Enzyme System; D003579:Cytochrome Reductases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010634:Phenobarbital