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Evaluation of metabolomic profiling against renal toxicity in Sprague–Dawley rats treated with melamine and cyanuric acid

  • Organ Toxicity and Mechanisms
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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 [1H]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.

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Acknowledgments

We thank Dr. TS Kang for discussion that inspired us to perform this study. We also thank HG Jeong (College of Pharmacy, Chungnam National Univ.) and TC Jeong (College of Pharmacy, Yeungnam Univ.) for helpful comments on the manuscript. This study was supported by the grants from Korea Food and Drug Administration (KFDA), National Institute of Food and Drug Safety Evaluation (NiFDS), and National Research Foundation (NRF) of Korea (No. 20090083538).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan, 609-735, South Korea

    Tae Hyung Kim, Mee Young Ahn, Hyun Jung Lim, Young Ju Lee, Yu Jin Shin, Umasankar De, Jaewon Lee & Hyung Sik Kim

  2. Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, 609-735, South Korea

    Suhkmann Kim

  3. Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Chunchun-Dong 300, Changan-Ku, Kyunggi-Do, Suwon, 440-746, South Korea

    Byung Mu Lee

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  1. Tae Hyung Kim
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Kim, T.H., Ahn, M.Y., Lim, H.J. et al. Evaluation of metabolomic profiling against renal toxicity in Sprague–Dawley rats treated with melamine and cyanuric acid. Arch Toxicol 86, 1885–1897 (2012). https://doi.org/10.1007/s00204-012-0910-7

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  • DOI: https://doi.org/10.1007/s00204-012-0910-7

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