Bgugaine, a pyrrolidine alkaloid from Arisarum vulgare, is a strong hepatotoxin in rat and human liver cell cultures

Toxicity of bgugaine, a pyrrolidine alkaloid extracted from the tubers of A risarum vulgare, was studied in three different liver cell culture models: (I) the rat hepatocyte primary culture, (2) a liver epithelial cell line; a nd (3) the human hepatoblastoma cell line HepG(2). Cytotoxicity was evaluat ed by LDH release, MTT reduction and MDA production. DNA fragmentation was analysed by flow cytometry or DNA gel-electrophoresis. In hepatocyte and ep ithelial cell cultures, drug toxicity appeared at 30 mu M and was evaluated by an increase in LDH release, a decrease in MTT reduction and a higher le vel of MDA production. Bgugaine concentrations lower than 30 mu M did not i nduce changes in these parameters. In HepG(2) cells. bgugaine treatment als o induced LDH release at concentrations of 40 and 50 mu M. DNA fragmentatio n, analysed in the HepG(2) cell line by flow cytometry, was observed in cul tures exposed to 50 mu M bgugaine. However, using DNA gel-electrophoresis, we demonstrated that lower bgugaine concentrations (10, 20 and 30 mu M) als o induced DNA damage. Our results show that: (1) bgugaine induces an import ant hepatotoxicity; (2) bgugaine toxicity is not mediated by a metabolic de rivative; and (3) bgugaine induces a significant DNA damage. Therefore, our data suggest that the alkaloid bgugaine contained in Arisarum vulgarae may be involved in the toxicologic symptoms observed after consumption of this plant tubers by humans and animals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.