title: Toxicokinetic study of melamine in the presence and absence of cyanuric acid in rats.
abstract: 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.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Li
authors.forename: Cong-Ran
authors.initials: CR
authors.lastname: Li
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Hu
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhai
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Zhang
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: You
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001806:Blood Urea Nitrogen; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012727:Sex Characteristics; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine