title: Effects of sodium citrate on melamine-cyanuric acid mixture-induced urolithiasis in rats.
abstract: BACKGROUND
  When melamine is used as an additive in infant formula, it may cause acute nephrotoxicity in humans as well as in other animals. This study was designed to examine the effects of a melamine-cyanuric acid mixture on cytotoxicity in vitro and rat-acute nephrotoxicity.
  
  
  METHODS
  In the in vitro study, crystal formations created by the melamine-cyanuric acid mixture were evaluated in media with differing pH conditions over a 24-h period and co-treatment with sodium citrate to observe the crystal formation. In the animal study, rats were exposed to a melamine-cyanuric acid mixture (400 mg/kg, 1:1) via oral gavage 14 days and co-treated with sodium citrate to observe the crystal formation in rats.
  
  
  RESULTS
  Melamine-cyanuric acid mixture-induced crystal was pH dependent in a conditioned medium, and sodium citrate could decrease the crystal formation. Melamine-cyanuric acid-treated rats showed marked kidney swelling, vacuolization and necrosis in the proximal tubules, and numerous polarizable crystals were located in the distal segments, causing increases in kidney weight, serum BUN and creatinine. After co-treatment with sodium citrate, these increases can all be reversed. Moreover, the degrees of nephrotoxicity, proliferating of cell nuclear antigen protein and urolithiasis-related osteopontin were also decreased in the kidneys.
  
  
  CONCLUSIONS
  Sodium citrate could decrease melamine-cyanuric acid mixture-induced crystal formation that leads to urolithiasis and nephrotoxicity in rats. These results may provide a strategy for melamine-cyanuric acid-intoxication therapy in animal.
authors.affiliation: Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yng-Tay
authors.initials: YT
authors.lastname: Chen
authors.forename: Shih-Ling
authors.initials: SL
authors.lastname: Hsuan
authors.forename: Bang-Ping
authors.initials: BP
authors.lastname: Jiann
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chou
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chang
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Lee
authors.forename: Maw-Sheng
authors.initials: MS
authors.lastname: Chien
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Lee
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
mesh_terms: D000818:Animals; D002951:Citrates / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D003460:Crystallization; D005260:Female; D005506:Food Contamination; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D053495:Osteopontin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077559:Sodium Citrate; D014227:Triazines / Q000737:chemistry / Q000633:toxicity*; D052878:Urolithiasis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002951:Citrates; D014227:Triazines; D053495:Osteopontin; D000077559:Sodium Citrate; D003404:Creatinine; C004632:cyanuric acid; C011907:melamine
keywords: Melamine and cyanuric acid; Nephrotoxicity; Sodium citrate; Urolithiasis