The Protection Of Alpha-lipoic On Cadmium-induced Toxicity In Liver And Kidney Of Rat

We carried out vivo studies on 100 g female SD rats to investigate the toxical effect of Cadmium on the function of Rats’liver and kidney, the protect effect of lipoic acid and the regulation role of gap junction intercellular communication (GJIC) in this process. After one week feeding, thirty rats were allocated randomly to three groups of ten each. The treatment of each group included control group, the rats consumed the DDW (Double Distilled Water) as drinking water; the cadmium group, the rats consumed the CdAc2 (50 mg/L) as drinking water; the cadmium and the a-lipoic acid treated group, besides consumed the CdAc2 as drinking water, the rats were also taken lipoic acid (50mg/kg.bw) by intragastric administration. ①Food consumption and weight were measured everyday during the treatments of 12 weeks. The Rat blood of orbital vein plexus was taken to detect the blood routine examination and the serum enzymes (ALB, AST, ALT, TP, ALP, BUN, UA) in the treatment of 4 week and 8 week.② After the rats were slaughtered by narcosis, we detected the blood routine and related biochemical parameters in serum. At the same time, At the end of the treatment, the content of the methane dicarboxylic aldehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) were detected.③The pathological and ultrastructural changes of the rats’liver and renal cortex were detected by optical microscope and transmission electron microscopy. ④The GJIC of the hepatocyte were detected by the incision loading dye-transfer assay. The Cx43, p-Cx43, Cx32 in the liver and kidney were measured by western blotting.⑤The gene transcription levels (Cx43, Cx32, Cx26mRNA) in liver and kidney were measured by Fluorescent Quantitative-PCR (FQ-PCR).The Red blood cell count, hemoglobin content and the indicators related to the function of liver and kidney (ALB、AST、ALT、BUN、UA、TP、ALP) had no significant differencesin the fouth week.. Interestingly, in eighth week and twelfth week, ALB, AST, ALT, BUN, UA of the Cd group were extremely significantly or significantly higher than that of control group (p<0.05 or p<0.01). While TP, ALP, the number of RBC (red blood cells) and HGB (hemoglobin) of the Cd group were extremely significantly or significantly lower than that of control group (p<0.05 or p<0.01). But the cadmium and the a-lipoic acid treated group had no obvious differences (p>0.05) compared to the control group.②After 12 weeks treatment, the activities of SOD, CAT, GSH-Px in the liver, kidney and serum of the Cd group decreased significantly or extremely significantly (p<0.05 or p<0.01) compared to the control group, while the content of MDA increased significantly (p<0.05). However the cadmium and the a-lipoic acid co-treated group had significantly differences or no differences (p<0.05 or p>0.05) compared to the control group. ③The obvious pathological changes in Cd group included the steatosis around hepatic vein and epithelial hyperplasia of bile duct in the liver, and the atrophy of glomerulus in renal cortex. While the slightly steatosis around hepatic vein and the granular degeneration in glomerulus epithelial cells were found in cadmium and the a-lipoic acid co-treated group. The uneven distribution of nucleus chromatin and mitochondrial swelling or dissappearance was observed under transmission electronic microscope in Cd group, while the cadmium and the a-lipoic acid co-treated group had slight changes.④The results of IL/DT indicated that the function of GJIC in Cd or Cd+a-LA group were inhibited (p<0.01). But the the function of GJIC in Cd+a-LA group was better than the Cd group (p<0.01). Compared to the control group, the expression level of Cx43 Cx32 and p-Cx43 levels in the liver or kidney of rats had decreased significantly or extremely significantly (p<0.05 or p<0.01) in Cd or Cd+a-LA group. Compared to the Cd group, the expression level of Cx43 Cx32 and p-Cx43 levels in the liver or kidney of rats in Cd+a-LA group had increased significantly or extremely significantly (p<0.05 or p<0.01). ⑤The relative mRNA transcription levels of Cx43, Cx32, Cx26 in were sigificantly lower than that in the control group (p<0.05 or p<0.01), while the transcription levels of these genes in Cd+a-LA group was higher than the Cd group (p<0.01).In conclusion:①All changes of the indices associated with the function of liver and kidney and blood routine examination demonstrated that a-lipoic acid had more clearly protect effect to Cd exposure along treatment.②Cd exposure could lead to decreased of the antioxidant enzyme activity and increase of lipid peroxidation products in serum and liver and kidney of rats. The a-lipoic acid improved the antioxidant function and protected of the toxicity induced by cadmium.③Cd exposure could result in obvious pathological changes or damges in the different tissues of the rats, liver and kidney were the severe organs, the nucleus and mitochondria in which were badly damaged particularly. The a-lipoic acid could reduce these damages.④Cd could decrease the expression of the proteins which were associated with the gap junction in kidney and liver. The a-lipoic acid could up-regulate the GJIC, which protected the the liver and kidney of the rats from the damage of the cadmium.