A Preliminary Study On The Toxic Effect Of Inorganic Arsenic Exposure On Mouse Liver And Its Mechanism

Arsenic(As)is a widely distributed metalloid element,which is mainly absorbed by people and animals through contaminated food,air or drinking water and accumulated in the body.It affects the liver,kidney,brain,spleen,skin and other tissues and organs of the body.Has a strong toxic effect.The liver is an important organ for detoxification and an important target organ for arsenic toxicity.At present,there are many studies on the toxicity of arsenic,but there is still little research on the body's own resistance feedback mechanism after the toxic effect of low concentration arsenic on the body.Therefore,this topic explored the toxic effects of arsenic exposure on mice and the possible body feedback resistance mechanism.In this study,three-week-old ICR mice were randomly divided into 9 groups of 10 mice,which were exposed to 0,AsIII(10,50,100,200 ?g/L)and AsV(10,50,100,200 ?g /L),after continuous exposure for 30 days,dissect,take blood and liver for related index detection.The specific experimental results are as follows:(1)Through continuous measurement of body weight and liver function indexes of mice,it was found that AsIII exposure reduced the Specific grow rate of mice,and the amount of body weight change in the AsIII treatment group was reduced compared with the blank control.The maximum reduction was 14.33% in the 200 ?g/L concentration group;Compared with the control group,the treatment group significantly increased serum ALT and AST levels.AsIII treatment group ALT and AST increased by 178%,294%,424%,140% and 28%,35%,17%,21%,respectively.AsV treatment group ALT and AST increased by 410%,268%,565%,772% and 28%,23%,52%,respectively.It showed that the liver of mice was damaged after arsenic exposure,and liver function was affected.(2)Through the detection of the expression of immune inflammation-related genes,it was found that the exposure of arsenic promoted the expression of IL-1?,IL-2,IL-6 and TNF-? mRNA in the liver of mice,and the exposure of arsenic induced the expression of inflammatory factors in the body.The body produces inflammation;At the same time,the body's immune-related immune gene expression increases to suppress inflammation.It showed that arsenic exposure had an inflammatory effect on the liver of mice and caused a certain effect on the liver immune system of mice.(3)The detection of antioxidative stress related enzyme activities and gene expression in mice revealed that: after exposure to arsenic,the MDA content in the mice liver was significantly increased by up to 96%;AsIII significantly inhibited the SOD activity in the mice liver,They were reduced by 14.1%,13.7%,17.8%,and 17.6%,respectively.At the same time,AsIII significantly inhibited Cu/Zn-SOD mRNA expression,and the change trend was consistent with SOD;Mn-SOD increased at 200 ?g/L.The Cu/Zn-SOD and Mn-SOD mRNA expression of AsV treatment group showed an overall increasing trend.AsIII inhibited the expression of MT-1 and MT-2 mRNA,and the expression of MT-1 and MT-2 mRNA in AsV treatment group increased at 200 ?g/L.The results showed that arsenic exposure induced mice to produce oxidative stress,which caused oxidative damage to the liver.The body itself regulated enzyme activity and related gene expression to remove peroxygen free radicals and resist stress.Comparing the experimental results of AsIII and AsV shows that the biological toxicity of AsIII is greater than AsV.(4)Through the detection of gene and protein expression of Nrf2-Keap1 signaling pathway in mice liver,it was found that the exposure of arsenic promoted the expression of mRNA of Nrf2,Keap1 and downstream HO-1,NQ01,GCLC and other mRNA regulated by mice liver.At the same time,the expression levels of Keap1 qualitative protein and Nrf2 nucleoprotein in mice liver are increased,which indicates that the oxygen free radical attack in mice liver generates oxidative stress and activates its own Nrf2-Keap1 signaling pathway,which exerts the body's antioxidant effect.Second,the protein expression levels of Nrf2 and Keap1 in AsIII treatment group were higher than those in AsV treatment group,indicating that AsIII was more biotoxic than AsV.\...