Free radical metabolism of ethanol has been suggested as a a-hydroxyethyl radical adduct in bile from animals administered factor in its hepatotoxicity. Although evidence of lipid radical formation due to ethanol treatment in vivo has been reported,[1-13C] ethanol and the spin trap POBN. Hyperfine coupling constants were aN 1 5.48, a 2.02, and a 4.61 G. In free radicals from ethanol itself have not been detected in living addition, an ethanol-dependent but 13C-invariant radical adduct, animals. However, by applying the EPA spectroscopy technique presumably lipid derived, was detected. Hyperfine coupling conof spin trapping to the study of ethanol-treated alcohol dehy- stants were 8N 1 5.38 and a 2.5 G. This report demondrogenase-deficient deermice(Peromyscus maniculatus), we strates, for the first time, the in vivo formation of the a-hydroxhave detected the ce-(4-pyridyl-i-oxide)-Nt-butylnitrone(POBN)/ yethyl free radical metabolite of ethanol.

Chronic ethanol abuse in humans produces widespread path- using EPR spectroscopy(8, 9). In vivo, the same technique of ological changes, including marked hepatic toxicity. The initial spin trapping has been applied to the study of free radical fatty changes in the liver were first attributed to lipid peroxi- metabolites from halocarbons, most recently in the detection dation by Di Luzio in 1963(1), and a number of subsequent of radical adducts in bile (18). Therefore, we have chronically studies have both supported and questioned the role of this pretreated ADH-deficient deermice with ethanol, administered process in toxicity(2-6). In 1972, Slater (7) suggested that the bolus doses of ethanol and the spin trap POBN, and examined metabolism of ethanol to a free radical, which could then the bile for radical adducts. initiate lipid peroxidation, might be a factor in hepatic damage. Albano et al.(8, 9) and Reinke et al.(6) have used EPR Materials and Methods