Study of the phase I and phase II metabolism of nephrotoxin aristolochic acid by liquid chromatography/tandem mass spectrometry

Wan Chan, Liang Cui, Guowang Xu, Zongwei CAI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

Prolonged exposure to aristolochic acid (AA) was shown to pose rapid progressive renal fibrosis in Belgian women in a slimming regime in the early 1990s. AA was also demonstrated to be strong carcinogen in rats. The carcinogenicity of AA is generally believed to be related to the nitro-reduction of AA, in which the aristolactam-nitriumion ion with a delocalized positive charge is the ultimate carcinogen. In this study, the phase I and phase II metabolism of AA was investigated by using an in vitro system with rat liver S9 and an in vivo animal study with Sprague-Dawley rats. AA was found to have been undergone hydroxylation, lactam formation, and desnitro and desmethyl transformations. Three conjugated metabolites of AA, namely the N- and O-glucuronides of aristolactams, were detected directly in pre-concentrated urine sample, with no acid hydrolysis or enzymatic digestion. Structural elucidation of the metabolites was performed by using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The results indicated that N-glucuronidation was the major phase II metabolic pathway for the aristolactams formed by AA after their nitro-reduction.

Original languageEnglish
Pages (from-to)1755-1760
Number of pages6
JournalRapid Communications in Mass Spectrometry
Volume20
Issue number11
DOIs
Publication statusPublished - 2006

Scopus Subject Areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry

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