Objectives Generation of large amount of ROS is considered to be a causative factor of structure damage or apoptotic in the myocardium and to be involved in the progress of exercise induced fatigue. ROS induce damage of DNA, enzymes, structural proteins, lipid peroxidation as well as disturb intracellular redox processes. antioxidant enzyme play a significant role in the antioxidant defense mechanisms operating in the heart. Ebselen is a seleno-organic compound which mimics the activity of the endogenous GPx and phospholipid hydroperoxide GPx. Protective effect of ebselen has been reported in various experimental in vivo and in vitro models of ischaemia, as well as in human ischaemic heart. The aim of this study was to investigate the effect of ebselen on the expression of cardiomyocytes apoptosis, the activity of antioxidant enzymes of SOD and GSH-Px, and the index of NO and NOS system in trained rat.
Methods Thirty male healthy SD rats were randomised into 3 groups, namely, the control group (A), exercise group (B) and exercise added ebselen group (C) with 10 rats in each group. Group C was gaster-poured by ebselen dissolved in 5% physiological saline solution with DMSO (50 mg/kg/d), and the two control group A and B preperfused with the same amount of placebo only. To establish the high-intensity and endurance-trained model for 8 weeks. The MDA, SOD, GSH-Px, NOS, iNOS, NO and other index of myocardiums of rats detected by routine methods, the expression of apoptosis protein Bcl-2 and Bax were detected using immunohistochemical staining.
Results Compared with control group, all above mentioned parameters in exercise group have notable changes, and the damage of cardiac structure are marked; After being interfered with ebselen, there are significantly improvement in the various index compared with exercise group, and the damage of cardiac muscle structure can be restrained effectively.
Conclusions Ebselen can inhibits the formation of superoxide anion, membrane phospholipid peroxidation after entering the cell by binding to mercapto functional group. Moreover, the author speculates that it has relationships between the increasing of expression of SOD and GSH-Px acylases in rat myocardium and ebselen’s participation in free radical metabolism of organism by imitating the activity of GSH-Px enzyme and reducing the consumption of the antioxidase system in vivo. Inhibition of apoptotic cell death by ebselen may be ascribed to reduction of active oxygen generation and oxygen free radicals for improving the antioxidation ability of the body and inhibiting the formation of NO after exercises. And these factors has been demonstrated to promote or induce the apoptosis. These findings may suggest that ebselen protected myocardium from the damage of apoptosis and free radicals in exercise and delayed the presence of exercise and its fatigue.