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J Appl Physiol (June 11, 2004). doi:10.1152/japplphysiol.00371.2004
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Submitted on April 6, 2004
Accepted on June 7, 2004

N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals

Ivan Medved1, Malcolm J Brown2, Andrew R Bjorksten3, Kate T Murphy1, Aaron C Petersen1, Simon Sostaric1, Xiaofei Gong1, and Michael J McKenna1*

1 School of Human Movement, Recreation & Performance; Centre for Aging, Rehabilitation, Exercise and Sport Science, Victoria University of Technology, Melbourne, Victoria, Australia
2 Department of Anaesthesia, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia
3 Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia

* To whom correspondence should be addressed. E-mail: michael.mckenna{at}vu.edu.au.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine and glutathione, and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight males completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71%VO2peak, then to fatigue at 92%VO2peak. NAC was intravenously infused at 125 mg.kg-1.h-1 for 15 min, then 25 mg.kg-1.h-1 for 20 min prior to and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status and cysteine concentration. A vastus lateralis biopsy was taken pre-infusion, at 45 min exercise and fatigue and analysed for NAC, total glutathione (TGSH), reduced glutathione (GSH) cysteine and cystine. Time to fatigue at 92%VO2peak was reproducible in preliminary trials (CV 5.6±0.6%) and with NAC was enhanced by 26.3±9.1% (NAC 6.4±0.6 vs CON 5.3±0.7 min, P<0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P<0.005). Muscle cysteine and cystine were unchanged during CON, but were elevated above pre-infusion levels with NAC (P<0.001). Muscle TGSH declined (P<0.05) and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P<0.05). Neither exercise nor NAC affected whole blood TGSH. Whilst blood GSH was decreased and calculated oxidised glutathione (cGSSG) increased with exercise (P<0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.




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