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Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

  • Son, Ji Yeon (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Kang, Yoon Jong (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Kyeong Seok (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Tae Hyung (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Lim, Sung Kwang (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Lim, Hyun Jung (College of Pharmacy, Pusan National University) ;
  • Jeong, Tae Cheon (College of Pharmacy, Youngnam University) ;
  • Choi, Dal Woong (Department of Public Health Sciences, Graduate School, Korea University) ;
  • Chung, Kyu Hyuck (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Byung Mu (Division of Toxicology, School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Hyung Sik (Division of Toxicology, School of Pharmacy, Sungkyunkwan University)
  • Received : 2014.03.29
  • Accepted : 2014.06.12
  • Published : 2014.06.30

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.

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