Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.
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PMID:Free radical scavengers and diaphragm injury following inspiratory resistive loading. 1167 24

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear; however, a number of recent studies have shown oxidative stress may be involved in its pathogenesis. The role of oxidative stress in CFS is an important area for current and future research as it suggests the use of antioxidants in the management of CFS. Specifically, the dietary supplements glutathione, N-acetylcysteine, alpha-lipoic acid, oligomeric proanthocyanidins, Ginkgo biloba, and Vaccinium myrtillus (bilberry) may be beneficial. In addition, research on food intolerance is discussed, since food intolerance may be involved in CFS symptom presentation and in oxidation via cytokine induction. Finally, recent evidence suggests celiac disease can present with neurological symptoms in the absence of gastrointestinal symptoms; therefore, celiac disease should be included in the differential diagnosis of CFS.
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PMID:Chronic fatigue syndrome: oxidative stress and dietary modifications. 1170 65

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an important source of free radicals in the hypoxic diaphragm. The effects of N-acetylcysteine (NAC; 18 mM), Tiron (10 mM), and the XO inhibitor allopurinol (250 microM) were studied on isometric and isotonic force generation during hypoxia (PO(2) approximately 7 kPa). NAC and Tiron decreased maximal force generation, slowed the shortening velocity, and decreased the power output. Fatigue rate was decreased in the presence of either NAC or Tiron. Allopurinol did not alter the contractility or fatigability of the diaphragm. During hyperoxia (PO(2) approximately 85 kPa), neither NAC nor allopurinol affected the contractility or fatigability of the diaphragm. Thus free radicals play a significant role in diaphragm contractility during hypoxia. Whether antioxidants exert a beneficial or harmful effect on muscle performance depends on the contraction pattern of the muscle. Free radicals generated by XO do not play a role in diaphragm contractility during either hypoxia or hyperoxia.
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PMID:Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase. 1170 36

Infusion of the antioxidant N-acetylcysteine (NAC) reduces fatigability in electrically evoked human muscle contraction, but due to reported adverse reactions, no studies have investigated NAC infusion effects during voluntary exercise in humans. We investigated whether a modified NAC-infusion protocol (125 mg. kg(-1). h(-1) for 15 min, then 25 mg. kg(-1). h(-1)) altered blood redox status and enhanced performance during intense, intermittent exercise. Eight untrained men participated in a counterbalanced, double-blind, crossover study in which they received NAC or saline (control) before and during cycling exercise, which comprised three 45-s bouts and a fourth bout that continued to fatigue, at 130% peak oxygen consumption. Arterialized venous blood was analyzed for glutathione status, hematology, and plasma electrolytes. NAC infusion induced no severe adverse reactions. Exercise decreased the reduced glutathione (P < 0.005) and increased oxidized glutathione concentrations (P < 0.005); NAC attenuated both effects (P < 0.05). NAC increased the rise in plasma K(+) concentration-to-work ratio (P < 0.05), indicating impaired K(+) regulation, although time to fatigue was unchanged (NAC 102 +/- 45 s; saline 107 +/- 53 s). Thus NAC infusion altered blood redox status during intense, intermittent exercise but did not attenuate fatigue.
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PMID:N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans. 1249 40

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated whether the antioxidant compound N-acetylcysteine (NAC) augments time to fatigue during prolonged, submaximal cycling exercise. Seven men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling exercise, comprising 45 min at 70% of peak oxygen consumption (Vo2 peak) and then to fatigue at 90% Vo2 peak. NAC was intravenously infused at 125 mg.kg-1.h-1 for 15 min and then 25 mg.kg-1.h-1 for 20 min before and throughout exercise, which was continued until fatigue. Arterialized venous blood was analyzed for NAC concentration, hematology, and plasma electrolytes. NAC induced no serious adverse reactions and did not affect hematology, acid-base status, or plasma electrolytes. Time to fatigue was reproducible in preliminary trials (coefficient of variation 7.4 +/- 1.2%) and was not augmented by NAC (NAC 14.6 +/- 4.5 min; control 12.8 +/- 5.4 min). However, time to fatigue during NAC trials was correlated with Vo2 peak (r = 0.78; P < 0.05), suggesting that NAC effects on performance may be dependent on training status. The rise in plasma K+ concentration at fatigue was attenuated by NAC (P < 0.05). The ratio of rise in K+ concentration to work and the percentage change in time to fatigue tended to be inversely related (r = -0.71; P < 0.07). Further research is required to clarify a possible training status-dependent effect of NAC on muscle performance and K+ regulation.
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PMID:Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise. 1295 60

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 men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min 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 preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined 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. Whereas blood GSH was decreased and calculated oxidized glutathione 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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PMID:N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. 1519 75

Fatigue of hand and forearm muscle groups can limit task performance by astronauts wearing space suits. Countermeasures to delay fatigue would therefore be useful to the space program. N-acetylcysteine (NAC) has been shown to inhibit fatigue during other tasks so we tested its effects during handgrip exercise. Volunteers practiced isometric handgrip maneuvers until performance was reproducible over three successive sessions (baseline). Performance then was retested after ingesting NAC (150 mg.kg(-1)) or saline. Drug administration increased NAC and cysteine blood levels (P < 0.001). Performance of sustained maximal efforts was unaffected. During repetitive submaximal efforts, NAC delayed fatigue (130% baseline) and inhibited glutathione oxidation. Saline did not alter glutathione status or performance of sustained maneuvers; repetitive task performance was increased by 15% (P < 0.05), a placebo effect. These data indicate that NAC supports glutathione homeostasis in exercising humans and may delay muscle fatigue during repetitive handgrip exercise. Our findings support oxidative stress as a causal factor in human muscle fatigue and argue for larger translational studies to define NAC effects on human performance.
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PMID:Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise. 1602 22

Sepsis impairs diaphragmatic contractility and endurance capacity and increases diaphragmatic fatigability. Several investigations have shown that administration of a number of free radical scavengers, such as N-acetylcysteine (NAC), protects the diaphragm from the development of endotoxin-mediated diaphragmatic dysfunction. The aim of this study was to evaluate the effects of melatonin (CAS 73-31-4), a naturally occurring potent antioxidant, on diaphragmatic contractility and lipid peroxidation as a marker of oxidative stress in endotoxemic rats. Rats were randomly divided into four groups: control group, endotoxemic group, melatonin group and endotoxemic plus melatonin group. Melatonin was administered by intraperitoneal injection 30 min before endotoxin inoculation to animals. Diaphragmatic function and malondialdehyde (MDA) level analysis as an indicator of lipid peroxidation were assessed 17 h after endotoxin or saline inoculation. Endotoxemia decreased the development of diaphragm fatigue and diaphragmatic MDA levels. The effects of endotoxemia on diaphragmatic contractions and fatigability were reversed and returned to control levels by melatonin administration. However, melatonin did not prevent the increase in muscle MDA content. In conclusion, the present study demonstrated that melatonin attenuated the endotoxin-induced impairment of diaphragm function. This effect of melatonin does not seem to be related to its antioxidant properties.
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PMID:Beneficial effects of melatonin on diaphragmatic contractility and fatigability in Escherichia coli endotoxemic rats. 1657 23

Reactive oxygen species (ROS) have been linked with both depressed Na(+),K(+)-pump activity and skeletal muscle fatigue. This study investigated N-acetylcysteine (NAC) effects on muscle Na(+),K(+)-pump activity and potassium (K(+)) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion 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. Subjects cycled for 45 min at 71% , then continued at 92% until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na(+),K(+)-pump activity (K(+)-stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K(+) and other electrolytes. Time to fatigue at 92% was reproducible in preliminary trials (c.v. 5.6 +/- 0.6%) and was prolonged with NAC by 23.8 +/- 8.3% (NAC 6.3 +/- 0.5 versus CON 5.2 +/- 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 +/- 2.8% at 45 min and by 23.9 +/- 2.3% at fatigue (P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%Deltaactivity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %Deltaactivity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K(+)] during exercise and the Delta[K(+)]-to-work ratio at fatigue were attenuated by NAC (P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K(+) regulation, and point to a role for ROS in muscle fatigue.
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PMID:N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans. 1690 38

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.
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PMID:Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice. 1800 75


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