Mechanism Study Of Selenium On The Liver Damage Induced By Beta-cypermethrin In Mice

Beta-cypermethrin is one of 80 synthetic pyrethroid insecticides currently.It disturbs normal nerve signal transmission by acting on sodium channels and potassium channels on animal nerve cell membranes,thus causing pests to convulse and die in farmland.At present,-CYP occupies the first place in the pyrethroid market.Due to the large amount of ?-C YP used in agriculture,it not only has adverse effects on the surrounding ecological environment,but also accumulates in agricultural products and nearby water bodies,causing potential hazards to animals and humans.Selenium is one of the essential trace elements in our body.It usually exists in the form of inorganic selenium and organic selenium in nature.It plays an important role in the growth and development of animal body and reproductive immunity.For animals,the optimum intake of Se is within a certain range,too low or too high is not conducive to health.At present,the researches on reducing or eliminating the toxicity of ?-CYP mostly focus on the harm of its residues to the body,and look for degrading bacteria with the ability to decompose ?-CYP from nature.However,few studies have been conducted on the toxic damage repair effect of?-CYP in animals,especially the recovery effect of Se on ?-CYP-induced liver injury has not been reported,and the transcriptomics of Se on ?-CYP-induced liver injury has not been discussed.In this study,inorganic selenium?Na₂SeO₃?and organic selenium?Se-SP?were used to study the effects of different forms of Se on liver injury in mice infected with B-CYP,respectively,to explore the recovery effects and molecular mechanisms of Se on liver injury caused by ?-CYP,and to lay a theoretical foundation for the rational use of Se in liver injury repair.The main contents include the following aspects:1.The effect of Se on the liver index in P-CYP treated miceCompared with the control group,the liver index in the ?-CYP injury group increased and the liver became swollen.Compared with ?-CYP injury group,both Na₂SeO₃ and Se-SP have the effect of reducing liver index,and the optimum concentration of Se is 50?g/kg.2.Effect of Se on antioxidant activity of liver in ?-CYP treated miceSe,as the active center of GSH-Px,can promote GSH-Px synthesis by increasing its concentration.At the same time,Se and necessary metal elements such as copper and zinc in SOD can synergistically promote absorption in animals,and lipid peroxide concentration will increase after oxidative damage.Therefore,the activities of SOD,GSH-Px and MDA can reflect the strength of antioxidant capacity in cells.Through the examination of liver tissue,we found that compared with the blank control group,SOD and GSH-Px activities in P-CYP injury group decreased,while MDA concentration increased.The cause of injury is that ?-CYP increases the level of reactive oxygen species?ROS?in cells,and lipid in peroxidation biomembrane generates more MDA,resulting in excessive pressure on the oxidative stress kinase activation system and decreased enzyme activity.In the repair group,the optimum concentration of Se for the recovery of GSH-Px by Na₂SeO₃ is 100?g/kg,and for the rise of SOD and the decline of MDA are both 50?g/kg.3.Repair effect of Se on the liver in ?-CYP treated miceIn the ?-CYP injury group,the enzyme activities of ALT and AST decreased in liver tissue,which was due to the leakage of contents caused by the large amount of ROS generated by ?-CYP attacking biomembrane.The concentrations of cholesterol,triglyceride and homocysteine increase due to the peroxidation effect which reduces the activities of various lipases.Observation of pathological sections of liver tissue showed that hepatocytes in the injured group showed vacuolization,nuclear deletion and even apoptosis.Na₂SeO₃ with Se concentration of 50?g/kg is the best concentration to increase ALT and AST in liver cells and reduce TC level,while Na₂SeO₃ with Se concentration of 100?g/kg is the best concentration to reduce TG level.Se-SP with 50?pg/kg Se concentration is the best concentration to increase ALT and AST and decrease TG and Hcy levels,and the best Se concentration to decrease TC concentration is only 25?g/kg.This shows that the nutrients contained in SP itself can restore liver injury.Both Na₂SeO₃ and Se-SP have the function of repairing liver function indexes,and the latter has more remarkable repairing ability.4.Transcriptome analysis of Se on the liver in ?-CYP treated miceThrough mRNA high-throughput sequencing,GO function analysis,qPCR and other methods,we screened and successfully verified 9 significantly differentially expressed genes:Cyp2b10,Cyp3a13,Cyp2j11 significantly increased in ?-CYP injury group,decreased in repair group,and Se-SP caused the decrease of these 3 genes to be larger than that of Na₂SeO₃.However,the expressions of Cyp26b1,Gm 13305,Stat4,Retsat,Socs2,Dhrs9 in the P-CYP injury group decreased significantly,and were up-regulated in different degrees in the repair group.Se-SP led to a higher increase in the expressions of Gm 13305,Socs2,and Dhrs9 genes than that of Na₂SeO₃,it indicates that Se-SP has a stronger regulatory effect on genes than Na₂SeO₃.Through pathway analysis,we screened linoleic acid metabolic pathway,JAK-STAT signal pathway,retinol metabolic pathway are closely related to these genes.To sum up,?-CYP and its metabolites affect the permeability of hepatocyte membrane through linoleic acid pathway,resulting in the decrease of intracellular ALT and AST concentrations and the increase TC and TG concentrations.At the same time,MDA increased and the activities of SOD and GSH-Px decreased.In addition,?-CYP oxidative damage destroys nuclear structural integrity and promotes cell apoptosis by inhibiting JAK-STAT signaling pathway.In addition,p-CYP affects cell survival by inhibiting retinol metabolic pathway.However,addition of Se could revised ?-CYP induced damage,promoted the recovery of liver.The comparison between inorganic selenium and organic selenium shows that Se-SP is not only better than SP,but also better than Na₂SeO₃.