title: Evaluation of renal toxicity by combination exposure to melamine and cyanuric Acid in male sprague-dawley rats.
abstract: Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Ji Yeon
authors: JY
authors: Son
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Yoon Jong
authors: YJ
authors: Kang
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Kyeong Seok
authors: KS
authors: Kim
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Tae Hyung
authors: TH
authors: Kim
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Sung Kwang
authors: SK
authors: Lim
authors: College of Pharmacy, Pusan National University, Busan, Korea.
authors: Hyun Jung
authors: HJ
authors: Lim
authors: College of Pharmacy, Youngnam University, Gyeongsan, Korea.
authors: Tae Cheon
authors: TC
authors: Jeong
authors: Department of Public Health Sciences, Graduate School, Korea University, Seoul, Korea.
authors: Dal Woong
authors: DW
authors: Choi
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Kyu Hyuck
authors: KH
authors: Chung
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Byung Mu
authors: BM
authors: Lee
authors: Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Hyung Sik
authors: HS
authors: Kim
keywords: Chronic toxicity; Cyanuric acid; Melamine; Mixture; Nephrotoxicity