Pine needle abortion in cattle: metabolism of isocupressic acid

The rumen and hepatic metabolism of the cattle abortifacient compound isocupressic acid (ICA) was examined in vitro and in vivo. ICA was incubated for 56 h in bovine rumen inoculum and was found to be converted to three compounds identified as imbricatoloic acid, a structurally uncharacterized isomer of imbricatoloic acid, and dihydroagathic acid. In preparations of liver homogenates, ICA was found to be oxidized to agathic acid. No differences in ICA metabolites were detected in comparing the cow, sheep, pig, goat, guinea pig, and rat livers; however, guinea pig and rat liver homogenates were less efficient in converting ICA to agathic acid. ICA had been administered to cows orally and by intravenous infusion and induced abortions after either method of treatment. After intravenous infusion, agathic acid was identified as the major metabolite together with minor amounts of dihydroagathic acid. After oral administration, dihydroagathic acid was identified as the major metabolite with minor amounts of agathic acid, imbricatoloic acid, and a structurally uncharacterized metabolite tentatively identified as tetrahydroagathic acid.