Does melamine exposure during infancy cause rhabdomyolysis?

We investigated the possible toxic effects of melamine on muscle tissue in rats using biochemical, hematological and histopathological methods. We used three groups of female albino Wistar rats. The first group was given 0.1 ml saline. The second and third groups were given 50 and 75 mg/kg melamine dissolved in 0.1 ml saline, respectively, daily for 21 days. On day 45, all rats were sacrificed, and whole blood and plasma were analyzed for hematologic and biochemical characteristics. Muscle samples were stained with hematoxylin and eosin for histopathological investigation. Other sections were immunostained for matrix metalloproteinase-9 (MMP-9) and type IV collagen. We found a significant increase in the lymphocytosis-compliant leukocyte number in the 75 mg/kg melamine group compared to the other groups. We also found significant decreases in the hemoglobin levels and hematocrit values in the 75 mg/kg compared to the other groups. We found that the 75 mg/kg melamine group exhibited a significant increase in plasma aspartate aminotransferase (AST) activity compared to the other groups. Changes in plasma creatine kinase and lactate dehydrogenase activity were not statistically significant. Plasma AST activity and mean corpuscular hemoglobin levels were correlated with the lymphocyte:neutrophil ratio. We found mononuclear cell infiltration at the periphery of muscle bundles and in the connective tissue bundles in the melamine treated group. We found MMP-9 expression in muscle cell membranes and type IV collagen expression in degenerative connective tissue fibers. Whole blood, plasma and muscle tissue analysis indicated that the 75 mg/kg melamine group exhibited rhabdomyolysis that was associated with lymphocytosis and anemia. The underlying mechanisms by which melamine causes rhabdomyolytic effects remain unclear.