Experimental acute gastrointestinal disease caused by the pyrrolizidine alkaloid, lasiocarpine

Abstract

Severe intestinal atrophy was caused by the pyrrolizidine alkaloid lasiocarpine in sheep, rats and mice. There was inhibition of crypt cell mitosis leading to mitotic irregularities, abnormal large cells, syncytical cells in cysts and severe villous atrophy with ulceration. Disease occurred most frequently in the cranial portion of the small intestine, but it also occurred caudally after repeated injections and occasionally in the glandular part of the stomach. The lesions in the intestines are similar to those caused by radiation and radiomimetic agents. It is suggested that the local intestinal radiomimetic effect is due to local exposure to the pyrrole metabolite of lasiocarpine after excretion through the bile duct. It is also proposed that the development of abnormal intestinal cells is more rapid than hepatic megalocytosis because of the very rapid turnover of cells in the duodenum.