L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro

• Published in: Journal of applied physiology (1985) 2009-07, Vol.107 (1), p.211-216
• Main Authors: Ferreira, Leonardo F, Gilliam, Laura A. A, Reid, Michael B
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Animals; Antioxidants - pharmacology; Biological and medical sciences; Diaphragm - drug effects; Diaphragm - metabolism; Diaphragm - physiopathology; Fatigue; Fatigue - prevention & control; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Glutathione Disulfide - metabolism; Hypotheses; In Vitro Techniques; Male; Mice; Mice, Inbred ICR; Musculoskeletal system; Oxidation; Oxidation-Reduction; Oxidative Stress - drug effects; Oxygen; Pyrrolidonecarboxylic Acid - pharmacology; Thiazolidines - pharmacology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00001.2009

Department of Physiology, University of Kentucky, Lexington, Kentucky Submitted 2 January 2009 ; accepted in final form 30 April 2009 Fatiguing exercise promotes oxidation of intracellular thiols, notably glutathione. Interventions that oppose or reverse thiol oxidation can inhibit fatigue. The reduced cysteine donor L -2-oxothiazolidine-4-carboxylate (OTC) supports glutathione synthesis and is approved for use in humans but has not been evaluated for effects on skeletal muscle. We tested the hypotheses that OTC would 1 ) increase reduced glutathione (GSH) levels and decrease oxidized glutathione, and 2 ) inhibit functional indexes of fatigue. Diaphragm fiber bundles from adult male ICR mice were incubated for 1 or 2 h at 37°C with buffer (control, C) or OTC (10 mM). N -acetylcysteine (NAC; 10 mM) was used as a positive control. We measured GSH metabolites and fatigue characteristics. We found that muscle GSH content was increased after 1-h incubation with OTC or NAC but was not altered after 2-h incubation. One-hour treatment with OTC or NAC slowed the decline in force with repetitive stimulation [mean (SD) fatigue index at 300 s: OTC = 34 ± 6% vs. C = 50 ± 8%, P < 0.05; NAC = 55 ± 4% vs. C = 65 ± 8%, P < 0.05] as did the 2-h OTC treatment (OTC = 38 ± 9% vs. C = 51 ± 9%, P < 0.05). These results demonstrate that OTC modulates the muscle GSH pool and opposes fatigue under the current experimental conditions. exercise; diaphragm; respiratory muscle; oxidative stress Address for reprint requests and other correspondence: M. B. Reid, Dept. of Physiology, Univ. of Kentucky, 800 Rose St., MS-508, Lexington, KY 40536-0298 (e-mail: michael.reid{at}uky.edu )