Metabonomic study of aristolochic acid-induced nephrotoxicity in rats

Minjun Chen, Mingming Su, Liping Zhao, Jian Jiang, Ping Liu, Jiye Cheng, Yijiang Lai, Yumin Liu, Wei Jia

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101 Scopus citations

Abstract

This paper describes a metabonomic study characterizing the nephrotoxicity induced by aristolochic acid (AA), a suspected kidney toxicant. For these studies, we examined the biochemical compositions of AA-treated rat urine using LC-MS and pattern recognition methods. The biochemical and histological patterns of rat groups treated with different AA sources showed distinct differences from those of the control group. Certain metabolic pathways, such as homocysteine formation and the folate cycle were significantly accelerated, while others, including arachidonic acid biosynthesis, were decreased. A subset-validation procedure using linear discriminant analysis (LDA) and selected predictive variables indicated that approximately 95% of the treated and nontreated rat urine samples were classified correctly into their respective treatment groups. The results suggested that this metabonomic approach is a promising methodology for the rapid in vivo screening of nephrotoxicity associated with ingesting multi-ingredient medicinal herb supplements, and provides a valid method for comprehending the chemical-induced perturbations in the metabolic network and the networked lesions.

Original languageEnglish
Pages (from-to)995-1002
Number of pages8
JournalJournal of Proteome Research
Volume5
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Keywords

  • Aristolochic acid
  • Caulis Aristolochiae manshuriensis
  • LC-MS
  • Metabonomics
  • Nephrotoxicity
  • Traditional chinese medicine

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