| In order to investigate the toxic effects of lead and cadmium on the liver of rats and the protective effect of ?-lipoic(?-LA)acid in this process,rat model was used in this study.100 g clean-grade inbred female SD rats were pre-fed for 1 week and randomly divided into 8 groups.(1)The control group was free to drink pure water;(2)Pb treatment group:rats consumed a solution of PbAc2(300mg/L)as drinking water.(3)Cd treatment group:rats consumed a solution of CdAc2(50mg/L)as drinking water.(4)Pb+Cd treatment group:rats received both Pb and Cd at the does,periods and ways of administration described above.(5)The Pb+?-LA treatment group:besides consumed the PbAc2 as drinking water,the rats were also taken ?-LA(50mg/kg.bw)by intragastric administration.(6)The Cd+?-LA treatment group:besides consumed the CdAc2 as drinking water,the rats were also taken ?-LA(50mg/kg.bw)by intragastric administration.(7)The Pb+Cd+?-LA treatment group:besides consumed the PbAc2 and CdAc2 as drinking water,the rats were also takena-LA(50mg/kg.bw)by intragastric administration.(8)?-LA treatment group were taken?-LA(50mg/kg.bw)by intragastric administration.Animals from each group were fed with conventional food pellets for 12 weeks.After the end of the exposure,following experiments:?Rats were sacrificed after exposure,weigh each group rats weight and liver weight,the change of the liver coefficient was calculated;?The contents of Cd,Pb,Cu,Fe,Zn and Mn in liver tissue were determined,the contents and vigour of antioxidant enzyme in liver tissue were determined;?The pathological and ultrastructural changes of liver tissue were observed by optical microscope and transmission electron microscope;?By fluorescence quantitative PCR method and western blot method in the detection of rat liver tissue autophagy related genes and proteins become bigger.The results are as follows:?At the end of the exposure,the liver of rats in each group had no obvious pathological changes.Compared with the control group,the liver coefficient of each exposure group showed varying degrees of decline,the Pb group and Pb+Cd group were significantly lower(P<0.05).Compared with the other groups,after adding ?-LA,the coefficient of liver tissue was significantly increased(P<0.01)and returned to the control level.?After exposure,compared with the control group,Cd and Pb+Cd group of cadmium content was significantly increased(P<0.01),after adding ?-LA the cadmium content of each group was significantly reduced(P<0.01);Compared with the control group,there was no significant changes of cadmium content in the other groups.Compared with the control group,Pb and Pb+Cd group lead content was significantly increased(P<0.01).After the addition of ?-LA,the lead content was significantly decreased compared with the other groups(P<0.01);There was no significant changes in lead content in other groups compared with the control group.?The results of optical microscope and electron microscope showed that there were significant histopathological changes in the liver tissues of all groups.There was a significant improvement compared with the exposure group after the addition of a-LA.?Compared with the control group,the contents of Mn,Cu and Zn in the liver tissues of the Pb,Cd and Pb+Cd group were significantly increased after exposure(P<0.01).Compared with the control group,the content of Fe in the Cd group and Pb+Cd group were significantly reduced,and there was no significant change in Pb group.?The content of CAT and the activity GSH riesd by lead and cadmium,SOD activity no change.?The mRNA and proteins expression levels of autophagy related genes Atg5,Atg7,Beclin-1 and LC3 in the exposed groups increased in different degrees compared with the control group,but there was no significant difference between the two groups.Compared with the control group,the expression of autophagy related genes in the exposed group increased significantly,and the protein expression in the combined group was significantly higher than that in the control group.The results illustrated that Lead and cadmium can cause liver damage which can be protected by autophagy induced by a-LA.Conclusion:Lead and Cadmium exposure can cause liver injury in rats,and oxidative stress is one of the ways to its toxicity and the liver can produce antioxidant enzymes to protect the body;Lead and Cadmium exposure increase liver autophagy levels;Lead and Cadmium have synergistic effect;a-LA can reduce the toxicity of Lead and Cadmium. |
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