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

• Published in: Toxicology letters Vol. 104; no. 3; pp. 239 - 248
• Main Authors: Rakba, Nafissa, Melhaoui, Ahmed, Loyer, Pascal, Guy Delcros, Jean, Morel, Isabelle, Lescoat, Gérard
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 22.02.1999; Amsterdam Elsevier Science
• Subjects: Alkaloids - toxicity; Animals; Arisarum vulgare; Bgugaine; Biological and medical sciences; Cells, Cultured; Chemical and Drug Induced Liver Injury; DNA - drug effects; DNA - metabolism; DNA Damage; Electrophoresis; Epithelial Cells - drug effects; Flow Cytometry; Hepatoblastoma - drug therapy; Humans; Liver cell cytolysis; Liver Neoplasms - drug therapy; Male; Medical sciences; Plant Extracts - toxicity; Plant poisons toxicology; Plants, Toxic - chemistry; Pyrrolidine alkaloid; Pyrrolidines - toxicity; Rats; Rats, Sprague-Dawley; Toxicology; Tumor Cells, Cultured; DMSO, dimethylsulfoxide; TE, tris-ethylene diamine tetracetic; MTT, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide]; Arisarum vulgare; MDA, malondialdehyde; LDH, lactate dehydrogenase; Pyrrolidine alkaloid; Bgugaine; HEPES, [4-(2-hydroxyethyl)-1-piperazine ethane sulfonic acid]; Liver cell cytolysis; Human; Monocotyledones; Rat; Toxicity; Liver; Rodentia; Cytotoxicity; In vitro; Pyrrolidine derivatives; Vertebrata; Alkaloid; Mammalia; Cell line; Araceae; Hepatocyte; Animal; DNA; Angiospermae; Plant origin; Digestive diseases; Epithelial cell; Spermatophyta; Tumor cell
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(98)00375-0

Toxicity of bgugaine, a pyrrolidine alkaloid extracted from the tubers of Arisarum vulgare, was studied in three different liver cell culture models: (1) the rat hepatocyte primary culture; (2) a liver epithelial cell line; and (3) the human hepatoblastoma cell line HepG 2. Cytotoxicity was evaluated by LDH release, MTT reduction and MDA production. DNA fragmentation was analysed by flow cytometry or DNA gel-electrophoresis. In hepatocyte and epithelial cell cultures, drug toxicity appeared at 30 μM and was evaluated by an increase in LDH release, a decrease in MTT reduction and a higher level of MDA production. Bgugaine concentrations lower than 30 μM did not induce changes in these parameters. In HepG 2 cells, bgugaine treatment also induced LDH release at concentrations of 40 and 50 μM. DNA fragmentation, analysed in the HepG 2 cell line by flow cytometry, was observed in cultures exposed to 50 μM bgugaine. However, using DNA gel-electrophoresis, we demonstrated that lower bgugaine concentrations (10, 20 and 30 μM) also induced DNA damage. Our results show that: (1) bgugaine induces an important hepatotoxicity; (2) bgugaine toxicity is not mediated by a metabolic derivative; 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.