| T-2 toxin is mainly produced by specific strains of Fusarium,such as Fusarium trifilum,Fusarium pseudomycoides,Fusarium pyrifolium,Fusarium pink,Fusarium graminearum and Fusarium snow rot.It belongs to class A of trichothecenes compound that has the strongest toxicity.Animals whom consumed the feed contaminated by T-2 toxin or long-term exposure to it may lead to acute and sub-chronic poisoning of immune system,hematopoietic system,circulatory system,metabolic system,reproductive system and etc.Consequently it causes great damage to the livestock and poultry industry.One of the important mechanism for T-2 toxin to exert its toxicity is to induce excessive production of free radicals in cells,which leads to oxidative stress in the body.Betulinic acid(BA)is a plant-derived pentacyclic triterpenoids with immune regulation,anti-inflammatory,anti-oxidative stress and many other biological activities.BA could alleviate oxidative stress induced by glucocorticoid and might have a positive effect on minimizing the oxidative injury in immunological system.However,the protective effect and the potential mechanism of BA on T-2 toxin induced oxidative injury has not been reported in literature.Objective:The main objective of the current study was to investigate the protective effect of BA on oxidative damage of immune organs induced by T-2 toxin in mice and its potential mechanism,which would provide the theoretical basis for further scientific research and livestock and poultry industrial application of BA.Methods:Total of 60 male Kunming mice were randomly divided into six groups as follow:control group;T-2 toxin group;low,medium and high doses(0.25,0.50,1.00mg/kg b.w.)of BA groups and the Vitamin E(VE)group(100mg/kg b.w.).BA and VE were suspended in1% starch jelly and administered orally daily for 14 d.The control and the T-2 toxin groups received 1% starch jelly with the same route of administration.Animals were received T-2toxin which dissolved in mixed solution of alcohol and PBS(alcohol: PBS = 1:12.5)intraperitoneally at the dose of 4 mg/kg b.w.to induce oxidative damage,while the control group was given the mixed solution of alcohol and PBS injections of the equal volume.Mice were executed to collect blood and lymphatic organs 15 h after last administration of T-2toxin.Hematology and blood biochemical indexes,the levels of reactive oxygen species(ROS),superoxidedismutase(SOD),glutathione(GSH),malondialdehyde(MDA)and total antioxidant capacity(T-AOC)in spleen and thymus were detected.Histomorphological changes of spleen and thymus were observed by H&E stain under a light microscope,and microstructure changes of spleen was observed by transmission electron microscope.Protein expression and phosphorylation of p38,ERK,JNK in MAPK signaling pathway,and protein expressions of Nrf-2,Keap1,HO-1 in Nrf-2/HO-1 signaling pathway were determined by Western blot.Results:1)Pretreatment with BA inhibited the increase of serum TC、TG and IgG levels induced by T-2 toxin(P< 0.01),and restored the number of white blood cells(P< 0.05)and lymphocytes(P< 0.01).2)BA pretreatment significantly reduced the accumulation of ROS level in spleen and thymus induced by T-2 toxin(P< 0.01).3)BA pretreatment enhanced SOD activity and decreased MDA content in spleen and thymus,and significantly increased T-AOC level in spleen and elevated GSH content in thymus(P<0.05).4)H&E stain of spleen and thymus showed that BA reduced inflammatory cell infiltration in spleen and decreased congestion in thymus.Ultrastructural observation of spleen showed that BA improved the morphology of mitochondria and enriched the number of organelles in splenocytes.5)BA administration suppressed the protein expressions and phosphorylation of p38,ERK,JNK in MAPK signaling pathway,as well as down-regulated protein expression of Keap-1and up-regulated protein expressions of Nrf-2 and HO-1 in Nrf-2-HO-1signaling pathway in spleen and thymus of mice treated with T-2 toxin.Conclusion:BA had protective effect on oxidative damage of immune organs induced by T-2 toxin in mice.The primary mechanisms underlying the prevention of BA on T-2-induced immune organs injury might be due to its alleviation of oxidative stress,possibly inhibiting MAPK signaling pathway and activating Nrf2-HO-1 signaling pathway. |
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