Metabonomic evaluation of melamine-induced acute renal toxicity in rats

Guoxiang Xie, Xiaojiao Zheng, Xin Qi, Yu Cao, Yi Chi, Mingming Su, Yan Ni, Yunping Qiu, Yumin Liu, Houkai Li, Aihua Zhao, Wei Jia

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The recent outbreak of renal failure in infants in China has been determined to be caused by melamine (Mel) and derivatives adulterated in the food. A metabonomic study was performed to evaluate the global biochemical alteration triggered by Mel ingestion in parallel with the acute renal toxicity in rats. Mel at 600, 300, and 100 mg/kg, cyanuric acid (Cya) at 100 mg/kg, and mixture of Mel and Cya (50 mg/kg each) were administered in five groups of Wistar rats, respectively, via oral gavage for 15 days. Urinary metabonomic profiles indicated that Mel perturbed urinary metabolism in a dose-dependent manner, with high-dose group showing the most significant impact. Metabonomic variations also suggest that the toxicity of low-dose (50 mg/kg) Mel was greatly elevated by the presence of Cya (at 50 mg/kg), which was able to induce a significant metabolic alteration to a level equivalent to that of 600 mg/kg Mel. Histological examination and serum biochemical analysis also indicated that the low-dose Mel-Cya mixture and high-dose Mel group resulted in the greatest renal toxicity. The high-dose Mel and low-dose Mel-Cya resulted in disrupted amino acid metabolism including tryptophan, polyamine, and tyrosine metabolism, and altered TCA and gut microflora structure.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalJournal of Proteome Research
Volume9
Issue number1
DOIs
StatePublished - Jan 4 2010
Externally publishedYes

Keywords

  • Cyanuric acid
  • Melamine
  • Metabonomics
  • Multivariate statistical analysis
  • Nephrotoxicity
  • Ultraperformance liquid chromatography/ time-of-flight mass spectrometry
  • Urine

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry

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