Article

Metabonomic Evaluation of Melamine-Induced Acute Renal Toxicity in Rats

Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, USA.
Journal of Proteome Research (Impact Factor: 5). 07/2009; 9(1):125-33. DOI: 10.1021/pr900333h
Source: PubMed

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.

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    • "rough the analysis of one or several kinds of bio�uids including serum, urine, saliva, and tissue samples, the global and dynamic alterations in metabolism can be deciphered [4]. erefore, metabolomics has been increasingly used in many applications such as identifying metabolite markers for clinical diagnosis and prognosis [5], monitoring the chemical-induced toxicity [6], exploring the potential mechanism of diverse diseases [7], and assessing therapeutic effects of treatment modalities [8] [9]. Univariate and/or multivariate statistical methods are routinely used in metabolomics studies, aiming at successful classi�cation of samples with metabolic phenotypic variations and identi�cation of potential biomarkers while minimizing the technical variations. "
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    • "Recent outbreak of renal failure in infants in China has been REVIEW determined to be caused by melamine and derivatives adulterated in the food. Metabonomics was performed to evaluate the global biochemical alteration triggered by melamine ingestion in parallel with the acute renal toxicity in rats (Xie et al. 2010). "
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    • "Low dose of melamine, such as 24 mg kg body weight and 33 mg kg body weight, had no significant effect on the change of body weight, neither did the formation of renal calculi (Kobayashi et al., 2010; Stine et al., 2011). Compared to the low dose of 100 mg kg body weight, melamine at 300 mg kg body weight could induce toxicity, however, it did not cause seriously damage induced by the high dose group of 600 mg kg body weight (Xie et al., 2010). In addition, referred to the effective dosage of latest study, melamine ingested by pregnant female rats at a dose of 400 mg/day bodyweight not only affected the female rats themselves but also could significantly affect plasma creatinine , plasma uric acid and blood urea nitrogen concentrations in their infant rats (Jingbin et al., 2010). "
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