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Preconditioning with ethyl 3,4-dihydroxy benzoate augments aerobic respiration in rat skeletal muscle

Authors Nimker C, P Singh D, Saraswat D, Bansal A

Received 22 December 2015

Accepted for publication 7 March 2016

Published 13 May 2016 Volume 2016:4 Pages 109—120


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Dörthe Katschinski

Charu Nimker, Deependra Pratap Singh, Deepika Saraswat, Anju Bansal

Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Timarpur, Delhi, India

Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model. We observed that EDHB supplementation increases aerobic metabolism via upregulation of HIF-mediated GLUT1 and GLUT4, thus enhancing glucose uptake in muscles. There was also a twofold rise in the activity of enzymes of tricarboxylic acid (TCA) cycle and glycolysis, ie, hexokinase and phosphofructokinase. There was an increase in citrate synthase and succinate dehydrogenase activity, resulting in the rise in the levels of ATP due to enhanced Krebs cycle activity as substantiated by enhanced acetyl-CoA levels in EDHB-treated rats as compared to control group. Increased lactate dehydrogenase activity, reduced expression of monocarboxylate transporter 1, and increase in monocarboxylate transporter 4 suggest transport of lactate from muscle to blood. There was a concomitant decrease in plasma lactate, which might be due to enhanced transport of lactate from blood to the liver. This was further supported by the rise in liver pyruvate levels and liver glycogen levels in EDHB-supplemented rats as compared to control rats. These results suggest that EDHB supplementation leads to improved physical performance due to the escalation of aerobic respiration quotient, ie, enhanced muscle respiratory capacity.

Keywords: cellular metabolism, exercise, ethyl 3,4-dihydroxybenzoate, prolyl hydroxylase enzyme

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