In vivo radical trapping and biliary secretion of radical adducts of carbon tetrachloride-derived free radical metabolites.

Products of the well documented reductive metabolism of CCl4 to .CCl3 have been examined by free radical trapping and ESR in vivo. We have found the phenyl-N-t-butylnitrone (PBN) radical adduct of .CCl3 in the bile of rats treated with the radical trap and 13CCl4. Hypoxia or pretreatment with phenobarbital has been reported to enhance the hepatotoxicity of CCl4 in vivo; these treatments also produced an increase in the biliary concentration of the PBN/.CCl3 radical adduct and in the .CCl3-derived PBN/.CO(-)2 radical adduct as well. A 13C-invariant spectrum detected upon PBN administration, with or without carbon tetrachloride, may be due to a lipid-derived species. ESR analysis of bile from animals treated with free radical traps and xenobiotics may prove useful in monitoring hepatic free radical-adduct formation in vivo.