title: Cytotoxicity, organ distribution and morphological effects of melamine and cyanuric acid in rats.
abstract: Melamine (Mel) is used widely as a basic organic chemical intermediate in several products. Within the last 10 years there have been two high-profile Mel exposures that caused toxicological concern, especially regarding food adulteration.
  
  
  OBJECTIVE
  This study aimed to determine the toxicity of Mel and one of its homologs, cyanuric acid (Cya), in vitro and in vivo.
  
  
  METHODS
  The IC50of Mel and Cya was determined by the MTT assay in NRK-52E and 293T cell lines. Organ-specific toxicity was assessed using the following dosing paradigm of Wistar rats: group 1: normal saline; group 2: Mel (180 mg/kg); group 3: Cya (150 mg/kg); and group 4: Mel (180 mg/kg) + Cya (150 mg/kg).
  
  
  RESULTS
  The NRK cell toxicity studies on Mel and Cya revealed IC50values of 1.89 mg/mL and 4.20 mg/mL, respectively. Similarly, Mel and Cya IC50values in 293T cells were 2.07 mg/mL and 3.71 mg/mL, respectively. Histopathologic studies revealed crystals in the renal medulla-cortex and loss of chief cells in the lining of the stomach in the group receiving Mel plus Cya. HPLC-MS analysis of organ homogenates showed that the concentration of Mel was greatest in the animals receiving a combination of both Mel and Cya.
  
  
  CONCLUSIONS
  Mel is more toxic than its homolog Cya. The kidney is the most affected organ. Mel was present at high concentration not only in the kidneys, but also in the uterus and liver, informing the scope of future studies on the mechanism of Mel and Cya toxicity.
authors.affiliation: a College of Clinical Medicine , Jilin University , Changchun , China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Sun
authors.affiliation: b Department of Thoracic Surgery , The First Hospital of Norman Bethune, Jilin University , Changchun , China.
authors.forename: Kaizhong
authors.initials: K
authors.lastname: Wang
authors.affiliation: c Department of Histology and Embryology , College of Basic Medical Sciences, Jilin University , Changchun , China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wei
authors.affiliation: d Laboratory Teaching Center of Basic Medicine , College of Basic Medical Sciences, Jilin University , Changchun , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: c Department of Histology and Embryology , College of Basic Medical Sciences, Jilin University , Changchun , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005835:Genitalia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009928:Organ Specificity; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D014018:Tissue Distribution; D014227:Triazines / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine
keywords: Cyanuric acid; ELISA; high performance liquid chromatography–tandem mass spectrometry; melamine; melamine cyanurate