title: Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid.
abstract: BACKGROUND
  Melamine was recently identified as a risk factor for renal calculi following the milk powder contamination in China. However, the long-term natural history of melamine exposure and its renal effects remain unknown. We evaluated renal function and other adverse health effects using a rat model administered melamine and cyanuric aid, considering age and sex.
  
  
  METHODS
  Twelve male F334/N rats each of ages 6, 10, and 26 weeks (N = 36) were equally assigned to Group M + C or controls. Group M + C rats were administered 12 mg · kg(-1) · day(-1) of melamine and cyanuric acid for 28 days. Serum and urine samples and kidney sections were evaluated on day 28. Six-week-old male and female F344/N rats were administered 12 mg of melamine and cyanuric acid for 28 days. Body weights were measured weekly; on days 0, 28, 90, and 180 after the 28-day period of melamine and cyanuric acid administration, serum samples and kidney sections were obtained.
  
  
  RESULTS
  Although the control group had no crystals, 6-week-old Group M + C rats had more crystals compared to the 10- and 26-week old Group M + C rats. Male rats also had significantly more crystals than females of the same age. Male rats were affected to a greater extent than females.
  
  
  CONCLUSIONS
  Younger rats experienced more severe renal failure and greater renal crystal deposition following melamine and cyanuric acid administration. However, after melamine and cyanuric acid administration cessation, crystal deposition and renal failure improved and did not cause growth arrest. Therefore, early diagnosis of melamine-associated calculi is critical.
authors: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. yasui@med.nagoya-cu.ac.jp.
authors: Takahiro
authors: T
authors: Yasui
authors: Takahiro
authors: T
authors: Kobayashi
authors: Atsushi
authors: A
authors: Okada
authors: Shuzo
authors: S
authors: Hamamoto
authors: Masahito
authors: M
authors: Hirose
authors: Kentaro
authors: K
authors: Mizuno
authors: Yasue
authors: Y
authors: Kubota
authors: Yukihiro
authors: Y
authors: Umemoto
authors: Noriyasu
authors: N
authors: Kawai
authors: Keiichi
authors: K
authors: Tozawa
authors: Bing
authors: B
authors: Gao
authors: Kenjiro
authors: K
authors: Kohri
mesh_terms: D000367:Age Factors; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003460:Crystallization; D004357:Drug Synergism; D042241:Early Diagnosis; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced / Q000473:pathology; D007669:Kidney Calculi / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D014227:Triazines / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014227:Triazines; D003404:Creatinine; C004632:cyanuric acid; C011907:melamine