title: Metabonomic evaluation of melamine-induced acute renal toxicity in rats.
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.
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Yi
authors.initials: Y
authors.lastname: Chi
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Ni
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Yumin
authors.initials: Y
authors.lastname: Liu
authors.forename: Houkai
authors.initials: H
authors.lastname: Li
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism* / Q000652:urine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D009929:Organ Size; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014227:Triazines / Q000633:toxicity*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine