N-acetylcysteine inhibits muscle fatigue in humans.

Abstract

Acute muscular fatigue is associated with the development of oxidative stress in humans. Strenuous contraction increases free radical production by human limb muscle (1) and fatiguing exercise alters biochemical indices of oxidative stress including glutathione status (2, 3) and markers of lipid peroxidation (4, 5). Such biochemical changes can be inhibited by chronic supplementation with antioxidant vitamins (4, 5) but nutritional supplements have not improved exercise performance (6-9). Thus, experiments to date have not determined whether oxidative stress is a cause of muscular fatigue in humans or simply an effect.In order to establish a cause/effect relationship, it is critical to demonstrate that exogenous antioxidants inhibit the loss of mechanical function during fatigue. This study tested this relationship using an experimental design that differs from previous human studies in two aspects. First, rather than using chronic nutritional supplements, we pretreated subjects with the nonspecific antioxidant N-acetylcysteine (NAC)' (10) by intravenous infusion immediately before fatiguing exercise. Second, rather than using volitional exercise to induce peripheral fatigue, we electrically stimulated tibialis anterior to repetitively contract under quasi-isometric conditions. This technique was developed previously (11) to evoke peripheral fatigue in the absence of central neural processes (e.g., inhibitory reflexes, coordination, motivation, learning) that can importantly influence volitional

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

“…Oral NAC supplementation in human subjects for two days (total dose 2.4 g) has been reported to decrease GSSG levels and blood lipid peroxidation indices provoked by an acute bout of exercise (93). Recently, Reid et al (20) showed that NAC administration improved muscle contractile functions and reduced low-frequency fatique in humans. Regardless of the mechanisms in the mentioned studies, supplementation of exogenous thiol sources has shown some clear merit in reducing oxidative stress during exercise (7).…”

Multiple Classes of Sulfhydryls Modulate the Skeletal Muscle Ca2+ Release Channel

“…Under basal conditions, unfatigued skeletal muscle produces reactive oxygen species (12) and nitric oxide (NO) derivatives (13,14) that have been shown to modulate excitation-contraction coupling (12,13). Strenuous contractile activity increases reactive oxidant production (14 -17), which contributes to fatigue of both isolated muscle preparations (15,16,18,19) and human muscle in vivo (20). Redox modulation of the ryanodine-binding protein has been proposed as a common mechanism for these effects (21).…”

Regulação metabólica e produção de espécies reativas de oxigênio durante a contração muscular: efeito do glicogênio na manutenção do estado redox intracelular

“…Em adição aos experimentos em que o efeito da suplementação de N-acetil-Lcisteína no estado redox plasmático foi estudado, em experimentos utilizando músculo diafragma de rato foi mostrado que o tratamento com N-acetil-L-cisteína atenua a fadiga muscular durante contrações agudas. Ao passo que, em humanos, a infusão de N-acetil-L-cisteína significativamente aumentou a força de contração muscular durante contrações intensas (fadigante) (60,61) .…”