Sun Huiying, Wang Kaizhong, Wei Haiyan, Li Zhe, Zhao Hui
a College of Clinical Medicine , Jilin University , Changchun , China.
b Department of Thoracic Surgery , The First Hospital of Norman Bethune, Jilin University , Changchun , China.
Toxicol Mech Methods. 2016 Sep;26(7):501-510. doi: 10.1080/15376516.2016.1201559. Epub 2016 Jul 17.
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.
This study aimed to determine the toxicity of Mel and one of its homologs, cyanuric acid (Cya), in vitro and in vivo.
The IC of 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).
The NRK cell toxicity studies on Mel and Cya revealed IC values of 1.89 mg/mL and 4.20 mg/mL, respectively. Similarly, Mel and Cya IC values 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.
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.
三聚氰胺(Mel)作为一种基本有机化学中间体被广泛应用于多种产品中。在过去十年中,发生了两起备受瞩目的三聚氰胺暴露事件,引发了毒理学关注,尤其是在食品掺假方面。
本研究旨在确定三聚氰胺及其同系物之一氰尿酸(Cya)在体外和体内的毒性。
采用MTT法在NRK - 52E和293T细胞系中测定三聚氰胺和氰尿酸的半数抑制浓度(IC)。使用以下Wistar大鼠给药方案评估器官特异性毒性:第1组:生理盐水;第2组:三聚氰胺(180mg/kg);第3组:氰尿酸(150mg/kg);第4组:三聚氰胺(180mg/kg)+氰尿酸(150mg/kg)。
对三聚氰胺和氰尿酸的NRK细胞毒性研究显示,IC值分别为1.89mg/mL和4.20mg/mL。同样,三聚氰胺和氰尿酸在293T细胞中的IC值分别为2.07mg/mL和3.71mg/mL。组织病理学研究显示,接受三聚氰胺加氰尿酸的组中,肾髓质 - 皮质出现晶体,胃黏膜主细胞丢失。对器官匀浆的HPLC - MS分析表明,在同时接受三聚氰胺和氰尿酸的动物中,三聚氰胺浓度最高。
三聚氰胺比其同系物氰尿酸毒性更大。肾脏是受影响最严重的器官。三聚氰胺不仅在肾脏中浓度高,在子宫和肝脏中也有较高浓度,这为未来三聚氰胺和氰尿酸毒性机制的研究范围提供了依据。