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J Appl Physiol 107: 1420-1430, 2009. First published September 10, 2009; doi:10.1152/japplphysiol.00668.2009
8750-7587/09 $8.00
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Effect of nandrolone decanoate administration on recovery from bupivacaine-induced muscle injury

James P. White,1 Kristen A. Baltgalvis,1 Shuichi Sato,1 L. Britt Wilson,2 and James A. Carson1

1Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, and ; 2Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina

Submitted 23 June 2009 ; accepted in final form 1 September 2009

Although testosterone administration elicits well-documented anabolic effects on skeletal muscle mass, the enhancement of muscle regeneration after injury has not been widely examined. The purpose of this study was to determine whether anabolic steroid administration improves skeletal muscle regeneration from bupivacaine-induced injury. Male C57BL/6 mice were castrated 2 wk before muscle injury induced by an intramuscular bupivacaine injection into the tibialis anterior (TA) muscle. Control mice received an intramuscular PBS injection. Anabolic steroid [nandrolone decanoate (ND), 6 mg/kg] or sesame seed oil was administered at the time of initial injury and continued every 7 days for the study's duration. Mice were randomly assigned to one of four treatment groups for 5, 14, or 42 days of recovery, as follows: 1) control (uninjured); 2) ND only (uninjured + ND); 3) bupivacaine only (injured); or 4) bupivacaine + ND (injured + ND). TA morphology, protein, and gene expression were analyzed at 14 and 42 days after injury; protein expression was analyzed at 5 days after injury. After 14 days of recovery, the injury and injury + ND treatments induced small-diameter myofiber incidence and also decreased mean myofiber area. The increase in small-myofiber incidence was 65% greater in injury + ND muscle compared with injury alone. At 14 days, injury + ND induced a fivefold increase in muscle IGF-I mRNA expression, which was greater than injury alone. Muscle Akt activity and glycogen synthetase kinase-3β activity were also induced by injury + ND at 14 days of recovery, but not by injury alone. ND had a main effect for increasing muscle MyoD and cyclin D1 mRNA expression at 14 days. After 42 days of recovery, injury + ND increased large-diameter myofiber incidence compared with injury only. Nandrolone decanoate (ND) administration can enhance castrated mouse muscle regeneration during the recovery from bupivacaine-induced injury.

muscle regeneration; anabolic steroids; myotoxin



Address for reprint requests and other correspondence: J. A. Carson, Dept. of Exercise Science, Public Health Research Center, Univ. of South Carolina, 921 Assembly St., Rm. 405, Columbia, SC 29208 (e-mail: carsonj{at}sc.edu).







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