Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats

Title
Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats
Author(s)
정태천김기환강미정노금한오도경강원구[강원구]정혜광[정혜광]이광열[이광열]김항건[김항건]김형식[김형식]
Keywords
CHROMATOGRAPHY/TANDEM MASS-SPECTROMETRY; RENAL CRYSTAL-FORMATION; SPRAGUE-DAWLEY RATS; LIQUID-CHROMATOGRAPHY; CATS; DOGS; PHARMACOKINETICS; METABOLISM; EXCRETION; TOXICITY
Issue Date
201412
Publisher
TAYLOR & FRANCIS INC
Citation
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v.77, no.22-24, pp.1346 - 1358
Abstract
To investigate the nephrotoxic potential of melamine (MEL) and cyanuric acid (CA) in male Sprague-Dawley rats, 7-d repeated-dose studies were performed. The experimental groups of MEL100 and CA100 were orally administered with MEL and CA at 100 mg/kg/d for 7 d, respectively. In groups dosed with MEL-CA mixtures, melamine and cyanuric acid (1:1) were simultaneously administered at 4, 20, or 100 mg/kg/d for 7 d (i.e., MEL-CA4, MEL-CA20, or MEL-CA100, respectively). Body weights were not markedly affected in MEL100, CA100, and MEL-CA4 groups, but significantly reduced in MEL-CA 20 and 100 rats. Most parameters determined in sera and tissues were not markedly altered in MEL100, CA100, and MEL-CA4-treated rodents. However, BUN, creatinine, total protein, and kidney weights were significantly increased in MEL-CA20- and MEL-CA100-treated animals. Renal histopathologic findings also revealed signs of toxicity, including tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration. Data suggested that the combination of MEL and CA might be responsible for observed nephrotoxicity that was not seen following individual exposure to either MEL or CA alone. Subsequently, the concentrations of MEL and CA were determined in serum, urine, and kidney tissues by using liquid chromatography-mass spectrometry. Toxicokinetic studies indicated that MEL or CA alone might be eliminated almost completely within 24 h after dosing showing no accumulation in kidney. However, the combined MEL-CA dose produced marked accumulation of chemicals in blood and kidneys. These results suggested that combined MEL and CA might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion.
URI
http://hdl.handle.net/YU.REPOSITORY/30374http://dx.doi.org/10.1080/15287394.2014.951592
ISSN
1528-7394
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약학대학 > 약학부 > Articles
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