Evaluation of renal toxicity by combination exposure to melamine and cyanuric acid in male Sprague-Dawley rats

Ji Yeon Son, Yoon Jong Kang, Kyeong Seok Kim, Tae Hyung Kim, Sung Kwang Lim, Hyun Jung Lim, Tae Cheon Jeong, DalWoong Choi, Kyu Hyuck Chung, Byung Mu Lee, Hyung Sik Kim

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalToxicological Research
Volume30
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Chronic toxicity
  • Cyanuric acid
  • Melamine
  • Mixture
  • Nephrotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Son, J. Y., Kang, Y. J., Kim, K. S., Kim, T. H., Lim, S. K., Lim, H. J., Jeong, T. C., Choi, D., Chung, K. H., Lee, B. M., & Kim, H. S. (2014). Evaluation of renal toxicity by combination exposure to melamine and cyanuric acid in male Sprague-Dawley rats. Toxicological Research, 30(2), 99-107. https://doi.org/10.5487/TR.2014.30.2.099