title: Hepatotoxicity and cholestasis in rats induced by the sesquiterpene, 9-oxo-10,11-dehydroageraphorone, isolated from Eupatorium adenophorum.
abstract: Eupatorium adenophorum leaves cause hepatotoxicity and cholestasis in rats. The hepatotoxicant has been characterized as 9-oxo-10,11-dehydroageraphorone (ODA), a cadinene sesquiterpene. Oral administration of ODA, mixed in feed to rats, caused jaundice in 24 h. The liver of the intoxicated animals had focal areas of hepatocellular necrosis, proliferation, and dilation of bile ducts with degenerative changes in the lining epithelium. There was marked increase in the conjugated form of plasma bilirubin and in the activities of the enzymes glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, glutamate dehydrogenase, and 5'-nucleotidase. The histopathological lesions in liver and biochemical profile of marker enzymes show that ODA induced hepatotoxicity and cholestasis in rats. This is the first report on the toxicity of a cadinene sesquiterpene in rats.
authors.affiliation: Department of Chemistry and Biochemistry, Himachal Pradesh Krishi Vishvavidyalaya, Palampur 176 062, HP, India.
authors.forename: R
authors.initials: R
authors.lastname: Bhardwaj
authors.forename: A
authors.initials: A
authors.lastname: Singh
authors.forename: O P
authors.initials: OP
authors.lastname: Sharma
authors.forename: R K
authors.initials: RK
authors.lastname: Dawra
authors.forename: N P
authors.initials: NP
authors.lastname: Kurade
authors.forename: S B
authors.initials: SB
authors.lastname: Mahato
mesh_terms: D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D002779:Cholestasis / Q000139:chemically induced*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008099:Liver / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000633:toxicity*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C098165:9-oxo-10,11-dehydroagerophorone; D012717:Sesquiterpenes