In vivo formation of a free radical metabolite of ethanol.
Free radical metabolism of ethanol has been suggested as a factor in its hepatotoxicity. Although evidence of lipid radical formation due to ethanol treatment in vivo has been reported, free radicals from ethanol itself have not been detected in living animals. However, by applying the EPR spectroscopy technique of spin trapping to the study of ethanol-treated alcohol dehydrogenase-deficient deermice (Peromyscus maniculatus), we have detected the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN)/alpha-hydroxyethyl radical adduct in bile from animals administered [1-13C]ethanol and the spin trap POBN. Hyperfine coupling constants were aN = 15.48, a beta H = 2.02, and a beta 13C = 4.61 G. In addition, an ethanol-dependent but 13C-invariant radical adduct, presumably lipid derived, was detected. Hyperfine coupling constants were aN = 15.38 and a beta H = 2.5 G. This report demonstrates, for the first time, the in vivo formation of the alpha-hydroxyethyl free radical metabolite of ethanol.
Knecht
K T
KT
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599-7365.
Bradford
B U
BU
Mason
R P
RP
Thurman
R G
RG
D000818:Animals; D001646:Bile / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005609:Free Radicals; D010542:Peromyscus
D005609:Free Radicals; D000431:Ethanol; D003676:Deferoxamine