TRICHLOROETHYLENE-INDUCED DEACTIVATION OF CYTOCHROME-P-450 AND LOSS OF LIVER GLUTATHIONE INVIVO

  • 1 January 1977
    • journal article
    • research article
    • Vol. 16  (1) , 109-120
Abstract
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% .times. 2 h). TRI caused morphologic liver injury only in the PBT animals. Cytochrome P-450 and b5 contents were diminished by the end of the 1st h or TRI exposure and NADH-cytochrome c reduction increased 3-fold by 8 h in the PBT animals. The only change in vehicle animals exposed to TRI was a decrease in NADPH-cytochrome c reductase activity by 8 h. Hepatic GSH contents of vehicle animals, constant during TRI exposure, rose with time. In constrast, the 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 2-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 h than their fasted counterparts. The hepatotoxic effects of trichloroethylene may be caused by inadequate detoxification of its relative intermediates.