Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
J Appl Toxicol. 2013 Jun;33(6):444-50. doi: 10.1002/jat.1764. Epub 2011 Nov 17.
Several lines of evidence show that the nephrotoxic effect of melamine (MEL) in animals is consistent with combined ingestion of MEL and cyanuric acid (CYA). The aim of the present study was to compare the toxicokinetics of MEL in the presence and absence of CYA, and to elucidate the correlation between toxicity and kinetic properties of MEL. Sprague-Dawley rats were administered a single oral dose of MEL (100 mg kg(-1) ) with or without CYA (100 mg kg(-1) ). Plasma and tissue samples were analyzed by liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay. Significant changes in toxicokinetic parameters of MEL such as lower maximum concentration (7.4 ± 3.5 vs 78.0 ± 11.0 µg ml(-1) ) and area under curve (94.9 ± 53.5 vs 295.1 ± 93.7 µg h ml(-1) ), higher plasma elimination half-life (7.0 ± 3.3 vs 2.5 ± 0.3 h) and volume of distribution (11 505.5 ± 5030.3 vs 1312.7 ± 337.7 ml kg(-1) ), as well as significantly higher concentration of MEL in rat kidney (2.96-274.15 vs < 1 µg g(-1) ) were detected in the CYA co-administration group when compared with MEL alone group (P < 0.05). The differences in kinetic parameters between the two groups meant that CYA co-administration could lower absorption, slow excretion and induce tissue accumulation of MEL, which correlated well with the generation and development of renal toxicity. In conclusion, co-administration with CYA leads to the alteration of the kinetic characteristics of MEL, which provides an additional explanation for renal toxicity.
有几条证据表明，三聚氰胺（MEL）在动物中的肾毒性作用与同时摄入 MEL 和三聚氰酸（CYA）一致。本研究的目的是比较 CYA 存在和不存在时 MEL 的毒代动力学，并阐明毒性与 MEL 动力学特性之间的相关性。SD 大鼠单次口服 MEL（100mg/kg）和/或 CYA（100mg/kg）。通过液相色谱-串联质谱法（LC-MS/MS）测定血浆和组织样品。MEL 的毒代动力学参数发生显著变化，如最大浓度（7.4±3.5 与 78.0±11.0μg/ml）和曲线下面积（94.9±53.5 与 295.1±93.7μg/h/ml）降低，血浆消除半衰期（7.0±3.3 与 2.5±0.3/h）和分布容积（11505.5±5030.3 与 1312.7±337.7/ml/kg）升高，以及大鼠肾脏中 MEL 浓度显著升高（2.96-274.15 与 <1μg/g），在 CYA 共给予组与 MEL 单独给予组相比（P<0.05）。两组间动力学参数的差异意味着 CYA 共给予可降低 MEL 的吸收，减慢排泄并诱导组织蓄积，这与肾毒性的产生和发展密切相关。总之，与 CYA 联合给予会改变 MEL 的动力学特征，这为肾毒性提供了额外的解释。
