Protective Effects and Possible Mechanism of Ebselen Pretreatment on the Rat Skeletal Muscle Structure and Function in High Intensity Endurance Training

Objective:Through analyzing the functional mechanism of ebselen in scavenging skeletal muscular reactive oxygen and reactive nitrogen and in regulating cell apoptosis during the process of fatigue in high-intensity endurance training, the research can provide experimental basis for ebselen to applied into the field of anti-fatigue.Methods:Thirty healthy male SD rats were randomly divided into the control group, exercise group and ebselen pretreatment exercise group after eliminate inadaptation treadmill exercise rats (n=8) .Ebselen pretreatment add exercise group was gaster-poured by ebselen dissolved in 5% physiological saline solution with DMSO (50mg/kg/d) , and the rest group were poured with the same amount of placebo only.After intensive endurance training on the treadmill for 8weeks, In situ DNA nick-end labeling (TUNEL) was used to detect apoptotic changes as an indicator of apoptosis.SOD, Cu/ZnSOD, GSH-Px, MDA, TAOC, NO, NOS, iNOS express levels were determined by kits.Bcl-2and Bax protein levels were estimated by immunohistochemistry.And skeletal muscle ultrastructure were illustrated with Transmission Electron Microscopy.Results:After intensive endurance training, the activity of endogenous antioxidant enzymes SOD, GSH-Px in the rat skeletal muscle decreased (P<0.05) , total antioxidant capacity TAOC decreased, the level of MDA increased (P<0.01) ;the content of NO and NOS was elevated and Bax/Bcl-2decreased (P<0.01) , apoptosis index AI increased (P<0.01) , the integrity of skeletal muscle ultrastructure was damaged significantly;Compared to the control exercise group, Ebselen pretreatment can increase the skeletal muscle SOD, GSH-Px activtiy, TAOC (P<0.05) and Bax/Bcl-2 (P<0.01) , decrease the level of MDA, NO and AI (P<0.01) , the ultrastructure of skeletal muscle received obvious protection.Conclusion:These findings may suggest that ebselen can protect the skeletal integrity of structure effectively, prolong the time that rat run on the treadmill until exhausted.The reason may be associated with that Ebselen can mimic activity of glutathione peroxidase, increase endogenous antioxidant enzyme activity in skeletal muscle, accelerate the degradation of reactive oxygen and reactive nitrogen species in the exercise, reduce the production of lipid peroxidation, inhibit the down-regulation of anti-apoptosis protein Bcl-2.