The effects of melamine with or without cyanuric acid on immune function in ovalbumin-sensitized mice.

Melamine is commonly used in the chemical industry, and it has been found to exist on food processing equipment and utensils. Previous investigations suggested that melamine alone or its combination with cyanuric acid appears to be toxic to immune system in animals. The objective of this study is to investigate the potential effects of melamine with or without cyanuric acid on immune function in ovalbumin- sensitized mice. Our data indicated that melamine-related administration caused a significant decreasing in the content of IL-4 in mice in comparison to negative control group. Significant increasing in the content of histamine (HIS) was recorded in almost all treated groups. The co-administration of melamine and cyanuric acid with high dose (each at 16mgkg-12d-1) led to a significantly lower contents of IL-10, IL-16 and monocyte chemoattractant protein-1 (MCP-1) in mouse serum in comparison to negative control group. Moreover, our data indicated that the number of Th1 and Th2 cells, and the ratio of Th1/Th2 spleen lymphocytes were significantly changed after treatment. Also, our results demonstrated that the profiles of both CD40 and CD40L were significantly altered in spleen lymphocytes after treatment.

The effects of melamine on humoral immunity with or without cyanuric acid in mice.

Melamine is an industrial chemical with high nitrogen content. When added to the pet food and milk it can falsely elevate the apparent protein concentration readings. Cyanuric acid related structurally to melamine has a strong mutual affinity with melamine. The combined ingestion of melamine and cyanuric acid was considered to be responsible for the crystalluria, kidney stones and subsequent renal failure in animals. In our previous investigation, we demonstrated that melamine alone or its combination with cyanuric acid appears to be toxic to the immune system in mice. The objective of this study was to investigate the potential effects of melamine on humoral immunity with or without cyanuric acid in mice. In comparison to control group, a significantly lower content of plasma cells expressing CD138 were observed in mixture groups of melamine and cyanuric acid with both middle and high doses. The co-administration of melamine and cyanuric acid resulted in a significant decreasing in blimp-1 protein expression and the contents of sIgA, C3, IL-21 and IL-4 compared with the control group. Moreover, our data clearly showed that melamine-related toxicity suppressed the production of IL-6 and IL-10 in a dose-dependent manner. Also, the animals from mixture of melamine and cyanuric acid with high dose group exhibited a significantly lower expression of gata-3 protein, The results from the present study suggested that the exposure to melamine alone or combination with cyanuric acid had certain humoral immunotoxicity in mice, especially when ingested in high dosage.

The toxic effects of melamine on spleen lymphocytes with or without cyanuric acid in mice.

Melamine is an organic nitrogenous compound whose acute toxicity was generally thought to be low in animals. In the present work, we investigated the potential cytotoxic effects of melamine on spleen lymphocytes in mice. In the treated group, morphological changes were observed in cultured lymphocytes in vitro. The co-administration of melamine and cyanuric acid caused a declining tendency in stimulation index of spleen lymphocyte. All treated groups had lower ratios of CD4+/CD8+. Both early apoptotic and late apoptotic/necrotic rates of lymphocyte were significantly higher in the co-administration high groups of melamine and cyanuric acid. Melamine-related toxicity promoted the expression of Bax mRNA, and suppressed the expression of Bcl-2 mRNA in spleen of the treated mice. These results provided useful information for assessing the toxicity of melamine on immune system of mammals, and contributed to the existing toxic profile of melamine.

The reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice.

Melamine, a chemical compound, was used widely in the manufacture of amino resins and plastics. Cyanuric acid related structurally to melamine was used as a water stabilizer in swimming pools. The combination of melamine and cyanuric acid was thought to be responsible for renal impairment in mammals. In the present work, we investigated the reproductive toxicity of melamine in the absence and presence of cyanuric acid in male mice. Pathological damages in different degrees were observed in the testis of male mice treated with different doses of both melamine alone and combination of melamine and cyanuric acid in a dose-dependent manner. Based on the TUNEL assay, the mice treated with high dose of melamine (50 mg/kg/day) had a significant increase in apoptotic index of spermatogenic cells (p<0.05) compared with the control group. Sperm abnormality test indicated that melamine alone resulted in abnormal sperm morphology. The mice from co-administration groups of melamine and cyanuric acid were not eating, and were most likely in renal failure. The combined exposure to melamine and cyanuric acid was revealed to have certain toxic effects on testis of male mice at a relative low dose (each at 1 mg/kg/day). Also, in comparison to melamine treated groups, more severe apoptosis was observed in co-administration groups of melamine and cyanuric acid with both middle (each at 5 mg/kg/day) and high doses (each at 25 mg/kg/day). However, all mice administrated with combination of melamine and cyanuric acid (each at 206, 412, or 824 mg/kg/day) died before day 6 from which no data were obtained on sperm abnormality. These results from this study demonstrated that melamine had certain toxic effects on testes of male mice, especially when ingested in high concentration. These results might be useful in evaluating the toxicity of melamine on reproductive system of male animal, and they also would be a supplement to the existing toxic profile of melamine.