A comparative study on the hepatic toxicity and metabolism of Crotalaria assamica and Eupatorium species

The oral LD50 of Crotalaria assamica, which contains mainly monocrotaline, was found to be 154 mg/kg in mice. Neither liver necrosis nor morbidity was demonstrated with Eupatorium extract at a dose level of 144 mg/kg, which was equivalent to the LD20 of Crotalaria. Pretreatment with phenobarbitone enhanced the toxicity of both plant extracts in mice. In in vitro studies, "metabolic pyrrole" was formed by incubating Eupatorium japonicum extracts with liver microsomes. The rate of "pyrrole" formation was similar to that of Crotalaria extract and pure monocrotaline alkaloid, but was much slower than retrorsine. The rate of N-oxide formation was, in descending order, retrorsine, Eupatorium japonicum and Crotalaria/monocrotaline. It is concluded that the alkaloid in Eupatorium species is metabolized to "pyrrole" and an N-oxide metabolite in the liver, but hepatotoxicity is much lower when compared with that caused by Crotalaria.