Impact of Melamine Exposure on Apoptotic Proteins and Oxidative Stress Markers in Mouse Hepatic Tissue

Abstract

Most melamine studies have focused on renal toxicity and its effects on the liver are still not well known. We investigated the apoptotic and oxidative effects of melamine on the liver using thirty BALB/c mice, divided into three groups. The control group received saline, while the low-dose melamine (LDM) group was given 400 mg/kg (1/8 LD50) and the high-dose melamine (HDM) group received 1600 mg/kg (1/2 LD50) intragastrically (0.25 ml) for 5 consecutive days. Liver Bcl-2 and caspase-3 expressions were analyzed at the protein level by immunohistochemistry and ELISA, and also at the gene level by quantitative Real-Time PCR. In addition, total antioxidant (TAS), total oxidant (TOS), and oxidative stress index (OSI) levels in liver tissues were measured spectrophotometrically. The immunohistochemical expression of caspase-3 was higher in the LDM and HDM groups compared to the control group (p = 0.002). TOS and OSI levels were increased significantly (P <0.05) in the HDM group as compared to controls. Bcl-2 ELISA levels in the HDM group increased significantly compared to the control (P = 0.0024). Caspase-3 values increased significantly in the HDM group compared to the control (P < 0.0001) and LDM (P = 0.0016) groups. This study provides evidence that exposure to melamine induces oxidative stress and increases apoptosis in the liver. In conclusion, we suggest that both apoptotic and anti-apoptotic mechanisms may be disrupted at high melamine exposures, which has not been reported extensively in previous publications.