College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
Laboratory of Animal Pathology and Public Health, College of Veterinary Medicine, China Agriculture University, Beijing, China.
Res Vet Sci. 2021 May;136:230-238. doi: 10.1016/j.rvsc.2021.03.002. Epub 2021 Mar 3.
The toxicity of melamine (MA) and its analogue cyanuric acid (CA) in multiple organs has been widely investigated. The purpose of this study was to characterize the pathological lesions of the liver caused by melamine alone or in combination with CA. Mice were oral administered 0, 25, 50, or 100 mg/kg/day MA and CA mixture (MC), or 25, 50, and 100 mg/kg/day MA alone for 7 days. We found MC caused increase of liver weight index and elevations of the serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cr). Histopathologically, both MA and MC caused scattered necrosis and inflammation cell infiltration in liver. Notably, at 100 mg/kg/day MC, melamine-related crystals were observed in hepatic sinusoid. The liver at high-dose MA and MC groups were further examined by TEM. There were marked degeneration of the mitochondria, and crystal deposition in the Disse space or cytoplasm of hepatic cells and Kupffer cells. TUNEL staining revealed that MA and MC caused apoptosis of hepatocytes and Kupffer cells. Western blotting showed the expression of Bcl-2 decreased, and Bax and caspase-3 increase in liver. The analysis of oxidative stress showed that the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) decreased, and the concentration of malondialdehyde (MDA) elevated in MA- and MC-treated mice. These results from this study demonstrated that both MA and MC caused pathological damage to the liver in mice, especially when ingested in high concentration.
三聚氰胺（MA）及其类似物氰尿酸（CA）的毒性已在多个器官中得到广泛研究。本研究旨在描述三聚氰胺单独或与 CA 混合物（MC）联合作用引起的肝脏病理损伤。小鼠经口给予 0、25、50 或 100mg/kg/天 MA 和 MC 混合物（MC），或 25、50 和 100mg/kg/天 MA 连续 7 天。我们发现 MC 导致肝重指数增加，血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和肌酐（Cr）浓度升高。组织病理学检查发现，MA 和 MC 均可引起肝脏散在性坏死和炎症细胞浸润。值得注意的是，在 100mg/kg/天 MC 组中，在肝窦中观察到与三聚氰胺相关的晶体。用 TEM 进一步检查高剂量 MA 和 MC 组的肝脏。线粒体明显变性，结晶沉积在 Disse 间隙或肝细胞和枯否细胞的细胞质中。TUNEL 染色显示 MA 和 MC 引起肝细胞和枯否细胞凋亡。Western blot 显示 MA 和 MC 处理后，Bcl-2 表达减少，Bax 和 caspase-3 增加。氧化应激分析表明，两种关键抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）的表达和活性降低，MA 和 MC 处理小鼠的丙二醛（MDA）浓度升高。本研究结果表明，MA 和 MC 均可引起小鼠肝脏的病理损伤，尤其是高浓度摄入时。
