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)

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

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

Bile accumulation in the peritoneal cavity after partial hepatectomy reduces hepatic regeneration. In 70% of hepatectomized rats with bile peritonitis, hepatic DNA synthesis showed a delayed initiation and diminished peak level. Because intraperitoneal bile significantly accelerated lipid peroxidation and decreased energy metabolism in the liver remnant, all hepatectomized rats with bile peritonitis died within 7 days. Subcutaneous administration of exogenous combined antioxidants SOD and catalase dramatically reduced lipid peroxidation and improved the survival rate. Although the slightly elevated serum endotoxin level in rats with peritonitis may play a role in the inhibition of hepatic regeneration, the result suggest that intraperitoneal accumulation of bile components may also directly accelerate lipid peroxidation in the liver remnant, inhibiting the hepatic regeneration.
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PMID:The degree of hepatic regeneration after partial hepatectomy in rats with peritonitis and the role of lipid peroxidation. 1023 31

Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species (ROS). Recent evidence suggests that radicals and other ROS are an underlying aetiology in exercise-induced disturbances in muscle redox status. These exercise-induced redox disturbances in skeletal muscle are postulated to contribute to both muscle fatigue and/or exercise-induced muscle injury. To defend against ROS, muscle cells contain complex cellular defence mechanisms to reduce the risk of oxidative injury. Two major classes (enzymic and non-enzymic) of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell. Primary antioxidant enzymes include superoxide dismutase (EC 1.15.1.1; SOD), GSH peroxidase (EC 1.11.1.9; GPX), and catalase (EC 1.11.1.6); these enzymes are responsible for removing superoxide radicals, H2O2 and organic hydroperoxides, and H2O2 respectively. Important non-enzymic antioxidants include vitamins E and C, beta-carotene, GSH and ubiquinones. Vitamin E, beta-carotene and ubiquinone are located in lipid regions of the cell, whereas GSH and vitamin C are in aqueous compartments of the cell. Regular endurance training promotes an increase in both total SOD and GPX activity in actively-recruited skeletal muscles. High-intensity exercise training has been shown to be generally superior to low-intensity exercise in the upregulation of muscle SOD and GPX activities. Also, training-induced upregulation of antioxidant enzymes is limited to highly-oxidative skeletal muscles. The effects of endurance training on non-enzymic antioxidants remain a relatively uninvestigated area.
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PMID:Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle. 1081 71

OBJECTIVE: To explore the possible mechanisms for the occurrence of diaphragm fatigue induced by diaphragm pacing. METHODS: The phrenic nerve of 8 dogs were exposed and subjected to stimulation with electric pulses emitted by a diaphragm pacemaker to induce diaphragm fatigue models, and the contents of ATP, ADP, AMP and AXP in the diaphragm muscles before and after diaphragm pacing were determined by high-performance liquid chromatography (HPLC). The contents of SOD and MDA were also measured and the morphological alteration of the mitochondria observed with transmission electron microscope. RESULTS: The contents of ATP, ADP, AXP and SOD were found significantly lower but MDA was higher during fatigue than those in normal conditions, while AMP content manifested no obvious change. Some mitochondria in the diaphragm muscles swelled and in a few cases, vacuolar degeneration was observed. CONCLUSIONS: The exhaustion and synthesis disturbance of ATP may explain the generation of diaphragm fatigue, and the reduction of dynamophore and ultrastructural injuries of the cells induced by oxygen free radicals may also contribute to this result.
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PMID:Changes in adenine nucleotide, SOD and MDA contents and mitochondria ulteractructure during diaphragm fatigue in dogs induced by diaphragm pacing. 1242 86

Skeletal muscle arterioles from obese Zucker rats (OZR) exhibit oxidant stress-based alterations in reactivity, enhanced alpha-adrenergic constriction, and reduced distensibility vs. microvessels of lean Zucker rats (LZR). The present study determined the impact of these alterations for perfusion and performance of in situ skeletal muscle during periods of elevated metabolic demand. During bouts of isometric tetanic contractions, fatigue of in situ gastrocnemius muscle of OZR was increased vs. LZR; this was associated with impaired active hyperemia. In OZR, vasoactive responses of skeletal muscle arterioles from the contralateral gracilis muscle were impaired, due in part to elevated oxidant tone; reactivity was improved after treatment with polyethylene glycol-superoxide dismutase (PEGSOD). Arterioles of OZR also exhibited increased alpha-adrenergic sensitivity, which was abolished by treatment with phentolamine (10-5 M). Intravenous infusion of phentolamine (10 mg/kg) or PEG-SOD (2,000 U/kg) in OZR altered neither fatigue rates nor active hyperemia from untreated levels; however, combined infusion improved performance and hyperemia, although not to levels in LZR. Microvessel density in the contralateral gastrocnemius muscle, determined via histological analyses, was reduced by approximately 25% in OZR vs. LZR, while individual arterioles from the contralateral gracilis muscle demonstrated reduced distensibility. These data suggest that altered arteriolar reactivity contributes to reduced muscle performance and active hyperemia in OZR. Further, despite pharmacological improvements in arteriolar reactivity, reduced skeletal muscle microvessel density and arteriolar distensibility also contribute substantially to reduced active hyperemia and potentially to impaired muscle performance.
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PMID:Impaired skeletal muscle perfusion in obese Zucker rats. 1285 17

Oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of ischemic heart disease patients. Recently, it was found that endurance training elevates protective heat shock proteins (HSPs) and antioxidant enzymes in skeletal muscle in healthy subjects and antioxidant enzymes in heart failure patients. However, it is unknown whether coronary ischemia and mild infarct without heart failure contributes to impairment of stress proteins and whether exercise training reverses those effects. We tested the hypothesis that exercise training would reverse alterations in muscle TNF-alpha, oxidative stress, HSP70, SOD (Mn-SOD, Cu,Zn-SOD), glutathione peroxidase (GPX), and catalase (CAT) due to chronic coronary occlusion of the left circumflex (CCO). Yucatan swine were divided into three groups (n = 6 each): sedentary with CCO (SCO); 12 wk of treadmill exercise training following CCO (ECO); and sham surgery controls (sham). Forelimb muscle mass-to-body mass ratio decreased by 27% with SCO but recovered with ECO. Exercise training reduced muscle TNF-alpha and oxidative stress (4-hydroxynonenal adducts) caused by CCO. HSP70 levels decreased with CCO (-45%), but were higher with exercise training (+348%). Mn-SOD activity, Mn-SOD protein expression, and Cu,Zn-SOD activity levels were higher in ECO than SCO by 72, 82, and 112%, respectively. GPX activity was 177% greater in ECO than in SCO. CAT trended higher (P = 0.059) in ECO compared with SCO. These data indicate that exercise training following onset of coronary artery occlusion results in recovery of critical stress proteins and reduces oxidative stress.
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PMID:Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion. 1687 55

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

Curcumin, a yellow pigment present in the Indian spice turmeric (associated with curry powder), has been linked with suppression of inflammation; angiogenesis; tumorigenesis; diabetes; diseases of the cardiovascular, pulmonary, and neurological systems, of skin, and of liver; loss of bone and muscle; depression; chronic fatigue; and neuropathic pain. The utility of curcumin is limited by its color, lack of water solubility, and relatively low in vivo bioavailability. Because of the multiple therapeutic activities attributed to curcumin, however, there is an intense search for a "super curcumin" without these problems. Multiple approaches are being sought to overcome these limitations. These include discovery of natural curcumin analogues from turmeric; discovery of natural curcumin analogues made by Mother Nature; synthesis of "man-made" curcumin analogues; reformulation of curcumin with various oils and with inhibitors of metabolism (e.g., piperine); development of liposomal and nanoparticle formulations of curcumin; conjugation of curcumin prodrugs; and linking curcumin with polyethylene glycol. Curcumin is a homodimer of feruloylmethane containing a methoxy group and a hydroxyl group, a heptadiene with two Michael acceptors, and an alpha,beta-diketone. Structural homologues involving modification of all these groups are being considered. This review focuses on the status of all these approaches in generating a "super curcumin.".
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PMID:Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. 1877 80

Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force-frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm(-2)) at stimulation frequencies of 20-300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in microm(2)) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with contractile dysfunction. Finally, the transgenic overexpression of independent endogenous antioxidants alters diaphragm skeletal muscle morphology, and these changes may also contribute to the diminished specific force production observed in these animals.
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PMID:Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery. 1978 18


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