title: On the mechanisms of glutathione depletion in hepatocytes exposed to morphine and ethylmorphine.
abstract: Incubation of isolated rat hepatocytes with either morphine or ethylmorphine resulted in glutathione (GSH) depletion followed by loss of cell viability. Pretreatment of cells with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase did not markedly affect the rates of GSH depletion seen in untreated cells. In contrast, hexobarbital stimulated H2O2 production in isolated liver microsomes, incubated aerobically with NADPH, whereas the effects of morphine and ethylmorphine on microsomal H2O2 production were minimal. Finally, incubation of hepatocytes with radioactively labeled morphine resulted in formation of 2 glutathione conjugates, one of which was tentatively identified as formyl glutathione. We conclude that GSH consumption during the metabolism of morphine or ethylmorphine by hepatocytes is due mainly to formation of glutathione conjugates.
mesh_terms: D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D005036:Ethylmorphine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006591:Hexobarbital / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009022:Morphine Derivatives; D009249:NADP; D009020:Morphine; D006591:Hexobarbital; D006861:Hydrogen Peroxide; D005980:Glutathione Reductase; D005978:Glutathione; D005036:Ethylmorphine; D002330:Carmustine