DEPRESSION OF LIVER MICROSOMAL GLUCOSE 6-PHOSPHATASE ACTIVITY IN CARBON TETRACHLORIDE-POISONED RATS - POTENTIAL SYNERGISTIC EFFECTS OF LIPID-PEROXIDATION AND OF COVALENT BINDING OF HALOALKANE-DERIVED FREE-RADICALS TO CELLULAR-COMPONENTS IN THE PROCESS

Depression of liver microsomal glucose-6-phosphatase (G6Pase) activity is a relevant feature of CCl4 poisoning. In vitro studies from severa l laboratories led to the hypothesis that a CCl4 promoted Lipid peroxi dation (LP) process is responsible for thai effect. In vivo studies fr om our laboratory with potent antioxidants in dosage regimes inhibitin g LP, however, were in contrast with that hypothesis. In this work we studied die potential preventive effects of Pyrazole (Pyr), alpha-toco pherol (alpha T), and 3-amino-1,2,4-triazole (AT) against CCl4-induced depression of G6Pase activity. Pyr decreases the intensity of the cov alent binding (CB) of CCl4 reactive metabolites to cellular components but does not inhibit LP in vitro or in vivo. alpha T inhibits LP in v itro and in vivo and AT inhibits both CB and LP. Our present studies g ive evidence that AT but neither Pyr nor alpha T are able to prevent t he CCl4-induced depression of G6Pase activity. Results are compatible with the hypothesis that the cooperation of both factors is critical t o explain the observed effects, and suggest that under in vitro experi mental conditions used by others the relevance of LP might be artifact ually promoted.