title: Antiulcer activity and subacute toxicity of trans-dehydrocrotonin from Croton cajucara.
abstract: The antiulcerogenic activity of trans-dehydrocrotonin (DHC), a nor-clerodane diterpene isolated from Croton cajucara Benth. (Euphorbiaceae), and its subacute (35 days) toxicity were studied in mice and rats, respectively. For the antiulcerogenic tests, models of gastric ulcers induced in mice by ethanol/HCl or stress were used. In both models, an oral dose of DHC (100 mg/kg) significantly reduced (P < 0.01) the formation of gastric lesions. DHC was also tested for its ability to scavenge free radicals, but no such action was observed in rat liver mitochondria. To assess the subacute toxicity, rats were treated orally with DHC (25, 50 and 100 mg/kg) for 5 weeks. A significant increase in liver weight was observed in male and female rats at highest doses, whereas a significant reduction in plasma alkaline phosphatase and cholesterol levels and an increase in gamma glutamyl transpeptidase were observed only at the highest dose (100 mg/kg) in female rats. DHC caused histopathological alterations in the liver that included a turbid tumefaction, microvacuolar degeneration and nuclear alterations. Despite the beneficial antiulcerogenic activity of DHC, our results suggest that the long-term use of this compound may induce liver damage.
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Rodríguez
authors.forename: Clélia A
authors.initials: CA
authors.lastname: Hiruma-Lima
authors.forename: Alba R M
authors.initials: AR
authors.lastname: Souza Brito
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D002784:Cholesterol / Q000097:blood; D029802:Croton / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D016166:Free Radical Scavengers; D006851:Hydrochloric Acid / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000897:Anti-Ulcer Agents; D045785:Diterpenes, Clerodane; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; C103060:dehydrocrotonin; D000431:Ethanol; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D006851:Hydrochloric Acid