The Protective Effect Of Vitamin E On Oxidative Damage Of Liver In Subchronic Cadmium Poisoning Rats

Cadmium（Cd）I s a toxic heavy metal environmental pollutant that can cause toxic damage to multiple organs in humans and animals.The liver is an important target organ for Cd poisoning.The toxicity of Cd to the liver is closely related to oxidative stress.Therefore,in order to reduce the oxidative damage of the liver caused by Cd,it has become the main research direction to search for a safe and effective antioxidant.Vitamin E（Vitamin E,VE）is an important antioxidant.Nrf2-mediated signaling pathways play an important role in cellular oxidative defense.At present,there have been some reports showing that VE combined with other antioxidants has a certain protective effect on Cd poisoning,but the protective effect of adding VE alone on Cd poisoning is less reported,and the relationship of Nrf2 signaling pathway in VE on liver oxidative damage in rats with Cd poisoning has not been reported.In this study,32 nine-week-old healthy male Sprague-Dawley rats were randomly divided into four groups,namely control,VE（100 mg/kg VE）,Cd（5 mg/kg Cd Cl₂）and VE+Cd（100 mg/kg VE+5 mg/kg Cd Cl₂）,and received intragastric administration of Cd and VE for 28 days.The effects of Cd on serum liver function-related enzyme（ALT and AST）activity,liver morphological structure,Cd content and oxidative stress levels,as well as VE protective effects were investigated by histopathological methods,atomic absorption spectrometry,biochemical methods,as well as relative real-time fluorescent quantitative PCR（RT-q PCR）and Western blotting analysis.The results were as follows:（1）Weight and weight growth results:After 28 days of experiment,the body weight and body weight growth rate of rats in Cd group were significantly reduced compared with the control group（P<0.05）,the body weight and body weight growth rate of rats in VE+Cd group were significantly increased compared with Cd group（P<0.05）,And the body weight of the VE+Cd group was not significantly different from that of the control group（P>0.05）.In addition,there was no significant difference in body weight and body weight growth rate between the VE group and the control group（P>0.05）.（2）The results of Cd and VE concentrations in the liver showed that:the content of Cd in the Cd group was significantly higher than that of the control group（P<0.05）,while that of the VE+Cd group was significantly lower than that of the Cd group（P<0.05）,but still significantly higher than that of the control group（P<0.05）.In addition,compared with the control group and the Cd group,VE and VE+Cd groups had significantly higher VE contents（P<0.05）.（3）The results of the liver weight,liver index and liver macrostructure showed that:at the 28 days of the experiment,the liver weights in the Cd group were significantly decreased compared with the control group（P<0.05）.The liver weight of the VE+Cd group increased significantly compared with the Cd group（P<0.05）,and there was no significant difference from the control group（P>0.05）.In addition,there was no significant difference in the liver index of rats among the four groups（P>0.05）.It can be seen from the general observation that the liver color of the Cd group rats is slightly lighter.Compared with the Cd group,the liver color and texture of the VE+Cd group were similar to the control group.（4）The results of serum liver function indexes（ALT,AST）showed that:the serum ALT and AST activities in the Cd group and VE+Cd group were significantly increased compared with the control group（P<0.05）.Compared with the Cd group,serum ALT and AST activities were significantly decreased in the VE+Cd group（P<0.05）.（5）Liver histopathological examination showed that:the histopathological alterations were observed in the Cd group,including granular and vacuolar degeneration of some hepatocytes,slightly disordered hepatic cord arrangement,narrowed hepatic sinusoids and a few pyknotic nuclei with condensed chromatin in some hepatocytes（Figure 1E,F）.The histopathological alterations mentioned above in the VE+Cd group were significantly alleviated compared with the Cd group.（6）The oxidative stress levels of the liver showed that:compared with the control group,the liver MDA content in the Cd group increased significantly（P<0.05）,while antioxidant enzyme（CAT,SOD and GSH-Px）activities and non-enzyme antioxidant GSH content and liver total antioxidant capacity（T-AOC）decreased significantly（P<0.05）.Compared with the Cd group,the change ranges of the above indicators in the VE+Cd group were significantly reduced（P<0.05）,but there was still a significant difference compared with the control group（P<0.05）.（7）The results of Nrf2 pathway related molecules detection showed that:compared with the control group,the m RNA and protein expression levels of Nrf2 and its downstream factors HO-1,NQO-1,GCLC,GCLM,GST were significantly reduced in the Cd group and VE+Cd group（P<0.05）.However,compared with the Cd group,the above indicators in VE+Cd group were significantly increased（P<0.05）.In conclusion,our results showed that administration of Cd Cl₂（5mg/kg/day）to rats by gavage for 28 days reduced the body weight,weight growth rate and liver weight were decreased,while serum ALT and AST levels were significantly increased.led to liver pathological damages,increased liver Cd accumulation and MDA level,decreased the total antioxidant capacity（T-AOC）,the activity of antioxidant enzymes and the content of GSH,together with the lowered m RNA and protein expressions of Nrf2 signal pathway related molecules.However,after supplementing VE（100 mg/kg）in advance before exposure to Cd in rats,the above indexes were significantly improved,suggesting that VE may improve the Cd-induced oxidative damage of liver by increasing the activity of antioxidant enzyme（CAT,SOD and GSH-Px）and non-enzyme antioxidant content,along with activating the Nrf2 signaling pathway.