Effects Of γ-oryzanol And Cysteamine On Redox Status And Immunity Of Stressed Mice

The body’s stress response caused by various forms of continuous stimulation may be accompanied by the occurrence of oxidative stress,which can cause oxidative damage to cells,tissues and even organs,and cause inflammation,which will adversely affect the body’s immune system,then further aggravate the body’s oxidative damage,which will eventually lead to the occurrence of a series of diseases.Therefore,the development of safe,efficient,and economical antioxidants is essential to alleviate oxidative stress in the body and improve immunity.The use of single antioxidants often has limitations such as strong dose dependence and narrow range of action.It is difficult to achieve the desired antioxidant effect when added at low doses.High doses will cause pro-oxidation effects,while composite antioxidants often show better effect.γ-oryzanol and cysteamine have been proved to have certain effects in anti-oxidation and anti-inflammatory aspects in previous studies.Considering the structural characteristics of γ-oryzanol which is highly fat-soluble,it may enter mitochondria--the main source of ROS to play a role,and cysteamine mainly exists in the cytoplasm.Therefore,the continuous stressed mouse model induced by the glucocorticoid prednisone was used in this experiment.In order to explore whether γ-oryzanol and cysteamine can play a synergistic role in combating oxidative stress and regulating immunity,different combinations of γ-oryzanol and cysteamine were added to the diet for intervention to study their effects on the redox state,internal redox state of mitochondria,mitochondrial function,immune function and intestinal health in stressed mice.It is expected to provide a reference for the development of safe and efficient compound antioxidants.The experimental design is as follows: 90 5-week-old male ICR mice were adaptively reared for one week and randomly divided into normal group,model group,oryzanol group,cysteamine group,combination 1 group and combination 2 group.Subcutaneous injections were given every two days.The normal group was injected with normal saline,and the other groups were injected with 40 mg/kg body weight of prednisone for modeling.The normal group and the model group were fed with normal diets.The supplementary amounts ofγ-oryzanol and cysteamine per kilogram of diet in the other four groups were 40 mg+0 mg,0mg+60 mg,20 mg+30 mg,and 40 mg+60 mg,respectively.The body weight was measured at the same time every week.In the 6th week of rearing,the sugar preference behavioral experiment was carried out on each group of mice,and the forced swimming behavioral experiment was carried out in the 7th week.After 8 weeks of rearing,they were sacrificed and sampled,and the stress status,redox status,mitochondrial function,immune and inflammatory status,intestinal morphology and other related indicators were determined to evaluate the effects of γ-oryzanol and cysteamine on the redox state and immune function of stressed mice and whether they have a synergistic effect.The study found that continuous stress caused slow weight gain,depression,a higher degree of stress response in the body,a significant decrease in antioxidant enzyme activity,a significant increase in lipid peroxidation,mitochondrial dysfunction,immune system damage,and intestinal inflammation,and the addition of different doses of γ-oryzanol and cysteamine could improve the situation to a certain extent.The results showed: Compared with the model group of mice,(1)the weight of the mice in the four experimental groups increased,their preference for sugar water increased,the immobility time during forced swimming was shortened,and the depression caused by continuous stress was improved.In addition,HPA axis-related hormone levels and HSP70 levels in heart,liver and jejunum decreased.Overall,the combination 1 group had the most obvious alleviating effect on stress conditions;(2)The activity of total SOD,CAT,GSH-PX and total antioxidant capacity in the four experimental groups of mice increased,and the MDA content in plasma and tissues decreased.In general,the combination 1 group had the most obvious effect on improving the redox state of stressed mice,and significantly increased the expression level of genes related to the Nrf2/ARE antioxidant signal pathway;(3)The Mn-SOD activity,mitochondrial membrane potential,A-Co A and ATP levels in the mitochondria of the four experimental groups of mice increased,the MDA content decreased.Mitochondrial DNA copy number,TFAM and PGC-1α gene expression levels increased.In general,the combination 1 group and oryzanol group had a significant effect on the redox state and mitochondrial energy metabolism in the mitochondria of stressed mice;(4)The spleen and thymus index,the content of immunoglobulin and anti-inflammatory factors in plasma and jejunum of the mice in the four experimental groups increased,the level of pro-inflammatory factors decreased,and the internal morphology and structure of the jejunum were improved.The expression level of genes related to the TLR4 signal pathway in the jejunum decreased,while the expression level of tight junction proteins related genes increased.In general,the combination 1 group had the most significant effect on improving immune dysfunction and inflammation in stressed mice,and effectively protected the integrity of the jejunal mucosal barrier.According to the results of all the above experiments,it can be found that the four experimental groups had a certain improvement effect on the redox status and immune function of stressed mice,and the combination 1 group had the most significant effect.It shows that when γ-oryzanol and cysteamine are used in combination at a lower dose,they may exert a synergistic effect in the body,play a good role in anti-oxidation and regulating immune function,thereby effectively resisting the harm caused by oxidative stress.