Modification of hepatic vitamin E stores in vivo. III. Vitamin E depletion by 1,2-dibromoethane may be related to initial conjugation with glutathione.
In the companion paper we demonstrated that hepatic vitamin E in rats becomes depleted and extrahepatic pools of vitamin E are altered by treatment with 1,2-dibromoethane (DBE). Vitamin E depletion may be dependent upon initial steps of DBE metabolism that are either oxidative (cytochrome P450 dependent) or conjugative (glutathione transferase dependent). That the liver content of glutathione (GSH) and vitamin E, the plasma concentration of vitamin E, and the serum activities of AST and ALT may be influenced by cytosolic metabolism of DBE was assessed by comparison of findings from rats treated with either 1,2-dichloroethane (DCE) or 1-bromo-2-chloroethane (BCE). The extent of oxidative metabolism was diminished by the use of tetradeutero-DBE (d4-DBE), and the availability of GSH for conjugative metabolism was diminished by pretreatment of rats with L-buthionine-S,R-sulfoximine (BSO) prior to treatment with DBE. Our results indicate that neither DCE nor BCE provokes a liver vitamin E depletion in rats, that d4-DBE treatment hastens but does not enhance the observed hepatic vitamin E depletion by comparison to animals treated with an equimolar dose of DBE, and that BSO pretreatment prevented the hepatic vitamin E depletion observed from animals treated with DBE alone. These results indicate that hepatic vitamin E depletion is the unique sequelae to conjugation of GSH with DBE, and we suggest the reactive episulfonium ion intermediate or a macromolecular adduct of this ion derived from DBE may play a role in liver vitamin E depletion associated with exposure to DBE.
Warren
D L
DL
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97330-6503.
Reed
D J
DJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D019328:Buthionine Sulfoximine; D015946:Ethylene Dibromide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors; D014810:Vitamin E / Q000097:blood / Q000378:metabolism*
D014810:Vitamin E; D008717:Methionine Sulfoximine; D015946:Ethylene Dibromide; D019328:Buthionine Sulfoximine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione