Effect of N-acetylcysteine on diaphragm fatigue

Abstract

It has recently been postulated that diaphragm fatigue may be due, at least in part, to a form of low-grade injury to subcellular organelles. Moreover, several studies have shown that thiol-containing compounds can protect cardiac and striated skeletal muscle organelles from the deleterious effects of a number of physiological stresses. The purpose of the present study was to determine whether pretreatment with N-acetylcysteine (NAC), a thiol-containing compound, would attenuate the rate of development of diaphragmatic fatigue. Studies were performed with the use of an in situ rabbit diaphragm strip preparation that permitted direct and continuous measurement of diaphragm tension development. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 30/min (20-Hz trains) for 20 min. The diaphragm force-frequency relationship (10-, 20-, 50-, and 100-Hz stimuli) was assessed immediately before and after fatigue trials and then again 20 min into the period of recovery. Half the animals were treated with intravenous NAC before fatigue, whereas the remaining animals were given intravenous saline. The rate of development of fatigue was markedly greater in saline-treated control than in NAC-treated animals, with reductions in tension of 55 +/- 3 and 34 +/- 3%, respectively, in these two groups of animals over 20 min (P less than 0.001). Although rhythmic stimulation resulted in a downward shift in the force-frequency relationship in both NAC- and saline-treated animals, the magnitude of this shift was substantially greater in saline-treated animals (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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).…”

Increased oxidative stress status in rat serum after five minutes treadmill exercise

“…Also, it was demonstrated that vitamin E could delay the onset of muscular fatigue [35]. Additionally N-acetylcysteine (NAC), which is also a very well recognized antioxidant, was also reported to prevent muscle fatigue in some experimental muscle preparations [36]. However, most of the studies regarding the positive effects of the antioxidants in this area of research are controversial, since some authors showed for example that both vitamin C and E did not affect in any way the performance of the exercise [4,37].…”

Effect of Whey Protein Isolate on Oxidative Stress, Exercise Performance, and Immunity

“…Other studies feeding NAC to rats (1g/kg/day) showed similar decreases in blood GSH oxidation following exhaustive exercise (71). Shindoh et al, (80) observed an increase in muscular performance with NAC supplementation in rabbit diaphragm muscle. Rabbits were treated with either intravenous NAC or saline.…”

“…However, one antioxidant, N-acetylcysteine (NAC), a known GSH booster, has improved performance in both animal and human models (see Table 1) (66,80). Indeed, direct GSH supplementation is ineffective in raising GSH because of its lipophobic properties and inability to cross cellular membranes (89).…”