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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have tested the hypothesis that diaphragm muscle fibers release superoxide anion radicals (O2-.) into the extracellular space. Fiber bundles were isolated from rat diaphragm and incubated in Krebs-Ringer solution containing cytochrome c (10(-5) M), a standard assay for O2-.. Bundles were either passive or active, i.e., directly stimulated to contract rhythmically. After 1 h, absorbance of reduced cytochrome c in the incubation medium was measured at 550 nm. Absorbance was greater in medium exposed to passive muscle than in medium without muscle (P < 0.01), indicating O2-. release by passive muscle. Absorbance was greater in medium exposed to active muscle than in that exposed to passive muscle (P < 0.01), an increase inhibited by superoxide dismutase (10(3) U/ml). Active bundles fatigued; bundles developing the lowest final stresses produced the greatest absorbance increases (P < 0.001), suggesting that the magnitude of fatigue was inversely related to O2-. release. We conclude that O2-. is released by diaphragm myocytes into the interstitium and surrounding medium, a process accelerated by fatiguing muscular contractions.
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PMID:Reactive oxygen in skeletal muscle. II. Extracellular release of free radicals. 133 53

We hypothesized that muscle fiber bundles produce reactive oxygen intermediates and that reactive oxidant species contribute to muscular fatigue in vitro. Fiber bundles from rat diaphragm were mounted in chambers containing Krebs-Ringer solution. In studies of intracellular oxidant kinetics, bundles were loaded with 2',7'-dichlorofluorescin, a fluorochrome that emits at 520 nm when oxidized; emissions were quantified using a fluorescence microscope. Emissions from unstimulated muscles increased over time (P < 0.001). Accumulation of fluorescence was slowed by addition of catalase (P < 0.001) or superoxide dismutase (P < 0.001) and was accelerated by repetitive muscular contraction (P < 0.05). To determine effects of reactive oxygen intermediates on fatigue, curarized bundles were stimulated to contract isometrically; force was measured. Catalase, superoxide dismutase, and dimethyl sulfoxide were screened for effects on low- and high-frequency fatigue. Antioxidants inhibited low-frequency fatigue [after 5 min of repetitive contractions, force at 30 Hz was 20% greater than control (P < 0.015)] and increased the variability of fatigue at 30 Hz (P < 0.03). Antioxidants did not alter high-frequency (200-Hz) fatigue. We conclude that 1) diaphragm fiber bundles produce reactive oxygen intermediates, including O2-. and H2O2; 2) muscular contraction increases intracellular oxidant levels; and 3) reactive oxygen intermediates promote low-frequency fatigue in this preparation.
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PMID:Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro. 147 54

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
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PMID:5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats. 153 18

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.
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PMID:Oxygen radical mechanisms of brain injury following ischemia and reperfusion. 175 40

We used in situ gastrocnemius muscle of anaesthetized dogs to test the hypothesis that O2 radical production during muscle contraction contributes to fatigue. Muscle tension was measured with a force transducer and blood flow was monitored with an electromagnetic flow probe. Muscle contractions were produced by stimulating the nerve for 15 min at 20 Hz, 12 trains/min, and a duty cycle of 0.25. Three groups of seven animals were given an infusion of 0.2 mL.min-1 of either saline, low-dose oxygen radical scavengers (250 IU.mL-1 superoxide dismutase, 640 IU.mL-1 polyethylene glycol (PEG)-catalase, 0.25 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol), or high-dose oxygen radical scavengers (3300 IU.mL-1 superoxide dismutase, 6600 IU.mL-1 PEG-catalase, 2.5 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol). Blood flow and vascular resistance of the gastrocnemius muscle during stimulation did not differ among groups. After 15 min of stimulation, the developed tension (represented as a percentage of initial tension developed) was 66 +/- 7% in the saline treated group, 70 +/- 6% in the low-dose group, and 70 +/- 4% in the high-dose group. The change in tension during recovery was not significant in the control or low-dose groups. However, there was partial recovery in the high-dose group. In conclusion, in this preparation, oxygen radical scavengers did not delay the development of decreased muscle tension.
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PMID:Failure of oxygen radical scavengers to modify fatigue in electrically stimulated muscle. 177 47

The changes of locomotor activities in rat loaded with swimming exercise were recorded by our newly devised apparatus. In addition, changes of lipid peroxide levels and their related enzyme activities in rat brain, liver as well as blood were studied. The results obtained were as follows: 1. The locomotor activities in rat recorded by the apparatus showed the same patterns as that reported by the other researchers. 2. After the loading of swimming, locomotor activities in rat during the dark period decreased significantly as compared to those of the control. 3. The levels of TBARS (thiobarbituric acid reactive substance), SOD (superoxide dismutase) and GSH-px (glutathione peroxidase) in rat liver elevated after the swimming exercise in the first group, which was sacrificed after loading with one treatment (about 5 hours) exercise of swimming. 4. The level of TBARS in rat brain elevated after the swimming exercise in the second group, which was sacrificed after loading with two treatment exercise of swimming. 5. The level of TBARS in plasma decreased, and GSH-px, GR (glutathione reductase) and catalase in red blood cells elevated in the third group, which was sacrificed after two-hour rest following the loading with two treatment exercise of swimming. It is indicated that our newly devised apparatus is useful for monitoring locomotor activities in rat, and that the fatigue in rat caused by swimming load can be shown in terms of changes in the above activities. The elevation of the level of TBARS during the swimming exercise observed in tissues of the brain and liver may suggest that the lipid peroxidation will reflect a certain state of fatigue in rat.
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PMID:[Changes of locomotor activities, lipid peroxide levels and their related enzyme activities in rat loaded with swimming exercise (author's transl)]. 727 88

Cold injury is a tissue trauma produced by exposure to freezing temperatures and even brief exposure to a severely cold and windy environment. Rewarming of frozen tissue is associated with blood reperfusion and the simultaneous generation of free oxygen radicals. In this review is discussed the current understanding of the mechanism of action of free oxygen radicals as related to cold injury during rewarming. Decreased energy stores during ischaemia lead to the accumulation of adenine nucleotides and liberation of free fatty acids due to the breakdown of lipid membranes. On rewarming, free fatty acids are metabolized via cyclo-oxygenase and adenine nucleotides are metabolized via the xanthine oxidase pathway. These may be the source of free oxygen radicals. Leukocytes may also play a major role in the pathogenesis of cold injury. Oxygen radical scavengers, such as superoxide dismutase and catalase, may help to reduce the cold induced injury but their action is limited due to the inability readily to cross the plasma membrane. Lipid soluble antioxidants are likely to be more effective scavengers because of their presence in membranes where peroxidative reactions can be arrested.
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PMID:The role of free radicals in cold injuries. 760 50

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.
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PMID:N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro. 796 Dec 53

The anti-fatigue effect of 50% ethanol extract ([M]) from the dried whole body of Agkistrodon blomhoffii blomhoffii Boie, was investigated using an acute weight-loaded forced swimming (AWLFS) test by monitoring swimming times, blood biochemical parameters, thiobarbiturate-reactive substances (TBARS) as an index of lipid peroxide and antioxidative enzyme activities in blood and tissue. [M] (500 mg/kg/d), given orally for three successive days, significantly prolonged swimming times. It also inhibited the elevation of TBARS in plasma, liver, brain, kidney and soleus, and inhibited the lowering of catalase activity in erythrocyte, liver and soleus. However, it had no inhibitory effect on the elevation of creatine-kinase activity, free fatty acid and lactic acid levels or on the decrease in glucose level in serum. Also, it decreased the plasma TBARS level and increased the superoxide dismutase activity of plasma and erythrocytes in normal rats. From these results, it can be considered that [M] has an anti-fatigue effect.
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PMID:Pharmacological study on Agkistrodon blomhoffii blomhoffii BOIE. V. anti-fatigue effect of the 50% ethanol extract in acute weight-loaded forced swimming-treated rats. 882 Sep 13

Recent studies have suggested that free radical scavenger administration reduces the rate of development of diaphragm fatigue. Much of this work has been done, however, using in vitro muscle preparations; the purpose of the present study was to assess the effect of scavengers on in vivo diaphragm contractile function. To accomplish this, we compared the rate of development of fatigue of the electrically stimulated diaphragm in four groups of dogs: (1) animals given intravenous polyethylene glycol adsorbed superoxide dismutase (PEG-SOD, 2,000 units/kg) 1 h before a fatigue trial; (2) a group given intravenous dimethylsulfoxide (DMSO, 0.5 ml/kg of a 50% solution) before fatigue; (3) a group given saline before fatigue; and (4) a group treated with denatured PEG-SOD (2,000 units/kg) before fatigue. We measured diaphragmatic concentrations of thiobarbituric acid reactive substances (TBAR), a marker of free radical-mediated lipid peroxidation, on muscle samples taken at the conclusion of fatigue trials. As a control, we also measured TBAR concentrations for muscle samples taken from nonfatigued diaphragm. We found that the rate of development of diaphragm fatigue was much greater in saline and denatured PEG-SOD-treated groups than for animals pretreated with either PEG-SOD or DMSO, with force falling to 23 +/- 4, 21 +/- 4, 50 +/- 7, and 47 +/- 6% of its initial value, respectively, over a 2-h period of electrophrenic stimulation in these four groups of animals (p < 0.01). TBAR concentrations in fatigued diaphragm from saline and denatured PEG-SOD-treated animals were significantly higher than levels for either nonfatigued fresh diaphragm or fatigued diaphragm taken from PEG-SOD- or DMSO-treated animals (p < 0.01). These data suggest that diaphragm fatigue resulting from repetitive low-frequency stimulation is associated with lipid peroxidation within this muscle and that pretreatment with free radical scavengers prevents lipid peroxidation and reduces the rate of development of fatigue.
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PMID:Effect of free radical scavengers on diaphragmatic fatigue. 903 4


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