title: Evaluation of metabolomic profiling against renal toxicity in Sprague-Dawley rats treated with melamine and cyanuric acid.
abstract: Melamine-induced renal toxicity is associated with crystal formation in the kidney following exposure to melamine and cyanuric acid. However, metabolomic profiling of intact kidney tissue after chronic intake of melamine and cyanuric acid (M + CA) mixtures has rarely been studied. The present study investigated the melamine-induced renal toxicity by determining metabolites in the kidney through [(1)H]nuclear magnetic resonance. Melamine (63 mg/kg) and cyanuric acid (6.3 mg/kg) were co-administered to rats via oral gavage for 30 days. The mixture of M + CA (63/6.3 mg/kg) induced nephrotoxicity, as determined by increased blood urea nitrogen (BUN) and creatinine levels. The kidney weights were significantly increased in the animals treated with M + CA (63/6.3 mg/kg). The histological analysis revealed epithelial degeneration and necrotic cell death in the proximal and distal tubules. Furthermore, various metabolites were altered in both renal medullar and cortical tissues. In the medullar tissues, asparagine, choline, creatinine, cysteine, ethanolamine, glucose, isoleucine, glutamine, and myo-inositol levels were elevated, but glucitol, phenylalanine, tyrosine, and sn-glycero-3-levels were reduced. In the cortex, ethanolamine, hypoxanthine, isoleucine and o-phosphoethanolamine levels were increased, whereas formate, glucose, glutathione, threonine, and myo-inositol levels were decreased, suggesting the M + CA-induced renal cell injury. These data suggest that a mixture of M + CA-induced metabolites may be useful biomarkers for the detection of kidney injury.
authors.affiliation: Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan, 609-735, South Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lim
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Shin
authors.forename: Umasankar
authors.initials: U
authors.lastname: De
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D001774:Blood Chemical Analysis; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D009929:Organ Size / Q000187:drug effects; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000633:toxicity*; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D014227:Triazines; C004632:cyanuric acid; C011907:melamine