期刊
JOURNAL OF PROTEOME RESEARCH
卷 9, 期 1, 页码 125-133出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr900333h
关键词
metabonomics; melamine; cyanuric acid; urine; nephrotoxicity; ultraperformance liquid chromatography/time-of-flight mass spectrometry; multivariate statistical analysis
资金
- International Collaborative Project of Chinese Ministry of Science and Technology [2006DFA02700]
- Team of Research Excellence Award, the Science and Technology Commission of Shanghai Municipality [06DZ05906]
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.
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