Protective Effect Of Betulinic Acid On Liver Injury Induced By T-2 Toxin In Mice

Objective:To study the protective effect and molecular mechanism of betulinic acid(BA)on liver injury induced by T-2 toxin in mice,and to provide important experimental basis and theoretical reference for the use of betulinic acid as an antidote of mycotoxin.Methods:The liver of mice was taken as the object of study.Different concentrations of betulinic acid(0.25 mg/kg,0.5 mg/kg,1 mg/kg)were added to the liver of mice at the same time.The antagonistic effect of betulinic acid on T-2 toxin induced liver injury in mice by oxidative stress was preliminarily studied by using the recognized water-soluble antioxidant VE as a positive control drug.(1)Protective effect of BA on oxidative damage of liver induced by T-2 toxin in mice: The activities of SOD,T-AOC,CAT and the contents of GSH and MDA in liver of mice were detected.(2)The protective effect of BA on liver injury induced by T-2 toxin in mice: The serum biochemical indexes of ALP,ALT,AST,TP and A/G in mice liver were detected.(3)The effect of BA on the pathological sections of mice liver induced by T-2 toxin.(4)The effect of BA on T-2 toxin-induced hepatocyte apoptosis in mice: TUNNEL assay was used to detect apoptosis in mice liver;Western Blot was used to detect the expression of mitochondrial apoptosis-related proteins Bax,Bcl-2,Caspase-3,P-STAT3,P-JAK 2 and JAK.Result:(1)T-2 toxin can cause oxidative damage to the liver of mice,reduce the activity of SOD,CAT,T-AOC and GSH content,and increase the content of MDA.When T-2 toxin combined with BA acted on the liver of mice,the activity of SOD,T-AOC,CAT and GSH content increased,while the content of MDA decreased.(2)T-2 toxin can cause liver injury in mice,decrease the value of TP and A/G,and increase the activity of ALP,ALT and AST.When T-2 toxin combined with BA acts on the liver of mice,the value of TP and A/G increases,while the activity of ALP,ALT and AST decreases.(3)After T-2 toxin treatment,the normal structure of the liver disappeared in pathological sections,and extensive necrosis of hepatocytes and obvious infiltration of inflammatory cells were observed.After BA treatment,apoptotic cells and inflammatory cells decreased significantly.(4)TUNNEL assay was used to detect apoptotic cells in T-2 toxin group.When T-2 toxin combined with BA acted on the liver of mice,apoptotic cells decreased in a dose-dependent manner.Compared with T-2 toxin alone,BA combined with T-2 toxin could down-regulate apoptotic signal pathway related proteins Bax,Caspase-3,P-STAT3,P-JAK2.The expression of Bcl-2/Bax was down-regulated and the expression of anti-apoptotic protein Bcl-2 was up-regulated.Conclusions:BA has protective effect on oxidative damage of liver induced by T-2 toxin in mice and can antagonize apoptosis of liver cells induced by T-2 toxin.