The pathologic lesions of liver caused by melamine alone or in combination with cyanuric acid in mice

Abstract

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.