Study Of Liver Injury Induced By Subchronic Aluminum Exposure In Rats

This study aimed to investigate the effects of subchronic aluminum(Al)exposure on structure and function of liver in rats. Sixty healthy, 110g¹20g,Wistar rats were divided randomly into four groups: control group(distilled water), low concentration(64.18mg/kg,Al³⁺), medium concentration(128.36mg/kg,Al³⁺), and high concentration(256.72mg/kg,Al³⁺). The model of subchronic aluminum exposure rat was made by having alminium with drinking water for 120 days. Clinical symptom, postmortem, organcoefficient, microstructure and ultrastructure of liver were observed. The activities of alanine transarninase ( ALT ) and glutamic-oxal(o)acetic transaminase(AST)and the concentrations of total protein(TP), albumin(ALB), total bilirubin(TBIL), direct bilirubin(DBIL), and total bile acid(TBA)in serums were detected using automatic biochemical analyzer. The activities of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD)and the concentrations of malondialdehyde(MAD) in serums and livers were detected by spectrophotometric method. The contents of Al, Fe, Zn and Cu in livers were measurede by using graphite furnace atomic absorption spectrophotometry and flame atomic absorption spectrophotometry. Hepatocyte apoptosis index was detected by Annexin V/PI with flow cytometry. The protein expressions of Bcl-2 and Bax in livers were detected by immunohistochemistry. The mRNA expressions of Bcl-2 and Bax in livers were detected by semiquantitative RT-PCR. The results were shown as follows.1. Depression, anorexia, slow-growing and fragility of liver were observed. The body weight and the organ coefficient of liver decreased with the increase of the dose of Al administration. It was proved that aluminum exposure could inhibit rats'growth and development.2. Under optical microscope, fatty degeneration, swell, confused of liver cells and pyknosis, splitting and solution of nucleus were observed. Under electron microscope, nucleus paramorphia, crimple, membrane invagination, increased lysosome, swollen and fused mitochondria were observed. Rough surface endoplasmic reticulum was decreased and lysosome was increased in intracytoplasm. It was proved that aluminium exposure could cause rat liver structure damage.3. The activities of ALT and AST and the concentration of TBA and TBIL were significantly lower and the concentrations of TP, ALB and DBIL were significantly higher in serums in the Al-treated rats than in the control ones. It was proved that aluminum expouse could damage metabolism, absorption, secretion, and protein synthesis function of rat liver.4. The the activity of GSH-Px and SOD were significantly lower and the concentrations of MDA were significantly higher in liver and serum in the Al-treated rats than in the control ones. It confirmed that aluminum could induce the oxidative stress. Accordingly, the antioxidant defence system of organism was destroyed and the free radical could not be removed, which further caused oxidative damage, and affected normal physiological function in rat liver.5. The contents of Al and Cu were significantly higer and the contents of Fe and Zn were significantly lower in liver in the Al-treated rats than in the control ones. It was proved that Al accumulated in the liver interfered with the metabolism of Fe, Zn, Cu and caused liver damage.6. Hepatocyte apoptosis index increased significantly in Al-treated rats than that in the control one. The expression of Bcl-2 protein and Bcl-2 mRNA decreased and the expression of Bax protein and Bax mRNA increased. Al-treated groups had significant differences from the control group. It was proved that aluminium exposure could induce hepatocyte apoptosis.