Hypoxia preconditioning by cobalt chloride enhances endurance performance and protects skeletal muscles from exercise-induced oxidative damage in rats

• Published in: Acta Physiologica Vol. 200; no. 3; pp. 249 - 263
• Main Authors: Saxena, S, Shukla, D, Khan, Y.A, Singh, M, Bansal, A, Sairam, M, Jain, S.K
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2010; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Animals; antioxidant; Antioxidants - metabolism; Biological and medical sciences; Cell Hypoxia; Cobalt - pharmacology; Creatine Kinase, MM Form - blood; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; exercise; Fundamental and applied biological sciences. Psychology; Glutathione - metabolism; Heme Oxygenase (Decyclizing) - metabolism; hypoxia mimetic; Lactic Acid - blood; Lipid Peroxidation - drug effects; Lipofuscin - metabolism; Male; Metallothionein - metabolism; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - metabolism; Mitochondrial Proteins - metabolism; muscle damage; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Diseases - etiology; Muscular Diseases - metabolism; Muscular Diseases - pathology; Muscular Diseases - physiopathology; Muscular Diseases - prevention & control; Necrosis; oxidative stress; Oxidative Stress - drug effects; Physical Endurance - drug effects; Physical Exertion; physical performance; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Physical exercise; Oxidative stress; hypoxia mimetic; Oxygen; Physical performance; Rat; Rodentia; exercise; Antioxidant; Striated muscle; Cobalt; Vertebrata; Mammalia; Chlorides; muscle damage; Hypoxia; Endurance; Preconditioning
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2010.02136.x

Training under hypoxia has several advantages over normoxic training in terms of enhancing the physical performance. Therefore, we tested the protective effect of hypoxia preconditioning by hypoxia mimetic cobalt chloride against exercise-induced oxidative damage in the skeletal muscles and improvement of physical performance. Male Sprague-Dawley rats were randomly divided into four groups (n = 8), namely control, cobalt-supplemented, training and cobalt with training. The red gastrocnemius muscle was examined for all measurements, viz. free radical generation, lipid peroxidation, muscle damage and antioxidative capacity. Hypoxic preconditioning with cobalt along with training significantly increased physical performance (33%, P < 0.01) in rats compared with training-only rats. Cobalt supplementation activated cellular oxygen sensing system in rat skeletal muscle. It also protected against training-induced oxidative damage as observed by an increase in the GSH/GSSG ratio (36%, P < 0.001; 28%, P < 0.01 respectively) and reduced lipid peroxidation (15%, P < 0.01; 31%, P < 0.01 respectively) in both trained and untrained rats compared with their respective controls. Cobalt supplementation along with training enhanced the expression of antioxidant proteins haem oxygenase-1 (HO-1; 1.2-fold, P < 0.05) and metallothionein (MT; 4.8-fold, P < 0.001) compared with training only. A marked reduction was observed in exercise-induced muscle fibre damage as indicated by decreased necrotic muscle fibre, decreased lipofuscin content of muscle and plasma creatine kinase level (16%, P < 0.01) in rats preconditioned with cobalt. Our study provides strong evidence that hypoxic preconditioning with cobalt chloride enhances physical performance and protects muscle from exercise-induced oxidative damage via GSH, HO-1 and MT-mediated antioxidative capacity.