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Abstract

ABSTRACT:Training under hypoxic conditions is known to enhance physical performance. The possible mechanism might be the stabilization of Hypoxia Inducible Factor (HIF), which otherwise is degraded under normoxia by the action of Prolyl Hydroxylase domain enzymes (PHD). Stabilization of HIF leads to upregulation of its target genes leading to improved erythropoiesis, angiogenesis and antioxidant status as an adaptation to combat training induced stress. Present study investigates efficacy of Ethyl 3, 4 Dihydroxybenzoate (EDHB) in stabilizing HIF-1α which leads to elevated levels of Vascular Endothelial Growth Factor, Erythropoetin, Hb and Hct, indicating improved angiogenesis and blood oxygen carrying capacity. In the present study we have reported 1.5 times increase in endurance performance in rats supplemented with EDHB with or without training as compared to respective controls. Significant improvement in antioxidant status as observed by increase in GSH, SOD, GST and decrease in MDA and protein oxidation, enhanced expression of anti-oxidative proteins Heme-Oxygenase, Metallothionein, Nuclear Factor Erythroid 2-Related Factor contributed in decreasing exercise training induced oxidative stress in EDHB supplemented trained rats. Enhanced levels of anti-inflammatory and reduced levels of pro-inflammatory cytokines might be additional factors responsible in decreasing muscle damage as observed by histopathological studies. The major outcome of the study is preconditioning with PHD inhibitor EDHB results in stabilization of HIF-1α, thus boosting erythropoiesis, antioxidant status and anti-inflammatory response which, in concert result in improvement of physical performance. The study thus underscores the potential of EDHB as a therapeutic agent for improving endurance performance by facilitating hypoxia adaptation in the skeletal muscle.