title: Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats.
abstract: The metabolic activation of aristolochic acids (AAs) that have been demonstrated to be mutagenic and carcinogenic was investigated. In vitro metabolism study indicated that AAs were metabolized to N-hydroxyaristolactam, which could be either reduced to aristolactams or rearranged to 7-hydroxyaristolactams via the Bamberger rearrangement. In vivo metabolism study is important because the intermediates (aristolactam-nitriumion) of the nitroreduction process are thought to be responsible for the carcinogenicity of AAs. Liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (MS/MS) were applied to the analyses of a series of positional isomers of hydroxyaristolactams in rat urine samples after the in vivo study of AAs. Three hydroxylated metabolites of aristolactam II and two hydroxylated metabolites of aristolactam I were identified. The structures of the positional isomers were elucidated from the interpretation of MS/MS spectra and theoretical calculations. In addition, several new metabolites were detected in the rat urine by high-resolution mass spectrometry and MS/MS, including those from the decarboxylation of AAs and the conjugations of acetylation, glucuronidation, and sulfation of aristolochic acid Ia.
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Chan
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yuen-Kit
authors.initials: YK
authors.lastname: Cheng
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D034341:Aristolochic Acids / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D034341:Aristolochic Acids; D002273:Carcinogens