Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.
Clin Chim Acta. 2013 Sep 23;424:76-82. doi: 10.1016/j.cca.2013.05.016. Epub 2013 May 28.
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.
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.
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.
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.
三聚氰胺作为添加剂用于婴儿配方奶粉时，可能会导致人类和其他动物出现急性肾毒性。本研究旨在探讨三聚氰胺-三聚氰酸混合物对体外细胞毒性和大鼠急性肾毒性的影响。
在体外研究中，评估了三聚氰胺-三聚氰酸混合物在不同 pH 条件下的培养基中在 24 小时内形成的晶体，并与柠檬酸钠共同处理以观察晶体形成。在动物研究中，大鼠通过灌胃暴露于三聚氰胺-三聚氰酸混合物（400mg/kg，1:1）14 天，并与柠檬酸钠共同处理以观察大鼠中的晶体形成。
三聚氰胺-三聚氰酸混合物诱导的晶体在条件培养基中依赖 pH，柠檬酸钠可以减少晶体形成。三聚氰胺-三聚氰酸处理的大鼠表现出明显的肾脏肿胀、空泡化和近端小管坏死，并且在远端段有大量可极化晶体，导致肾脏重量、血清 BUN 和肌酐增加。柠檬酸钠共同处理后，这些增加都可以逆转。此外，柠檬酸处理还降低了肾脏中的肾毒性、核抗原蛋白的增殖和结石形成相关的骨桥蛋白的程度。
柠檬酸钠可以减少三聚氰胺-三聚氰酸混合物诱导的晶体形成，从而导致大鼠的结石形成和肾毒性。这些结果可能为动物三聚氰胺-三聚氰酸中毒的治疗提供了一种策略。
