Catalase, superoxide dismutase, glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle

Kar, Nirmal C.; Pearson, Carl M.

doi:10.1016/0009-8981(79)90076-7

Cited by 100 publications

(32 citation statements)

References 19 publications

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“…But the data obtained from DMD studies are varied and are contradictory in some cases [5,6,9,14]. DMD pathology was associated with chronic oxidative stress, impairment of the redox-sensitive metabolic enzymes [13], decreased activity of both MnSOD and Cu/ Zn SOD and increased activity of GPx and GST [5,16].…”

Section: Discussionmentioning

confidence: 96%

“…Oxidative stress is one such mechanism implicated in MD but the contribution of this phenomenon has not been completely understood. In MD patients, altered antioxidant enzyme activities [5,6], lowered activity of mitochondrial complexes [7] and NFkappaB activation [8] have been demonstrated. Systemic [9,10] and muscle-specific [11] oxidative damage and altered anti-oxidant function have been reported in the muscles of DMD patients [12].…”

Section: Introductionmentioning

confidence: 97%

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Oxidative Damage in Muscular Dystrophy Correlates with the Severity of the Pathology: Role of Glutathione Metabolism

et al. 2012

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Muscular dystrophies (MDs) such as Duchenne muscular dystrophy (DMD), sarcoglycanopathy (Sgpy) and dysferlinopathy (Dysfy) are recessive genetic neuromuscular diseases that display muscle degeneration. Although these MDs have comparable endpoints of muscle pathology, the onset, severity and the course of these diseases are diverse. Different mechanisms downstream of genetic mutations might underlie the disparity in these pathologies. We surmised that oxidative damage and altered antioxidant function might contribute to these differences. The oxidant and antioxidant markers in the muscle biopsies from patients with DMD (n = 15), Sgpy (n = 15) and Dysfy (n = 15) were compared to controls (n = 10). Protein oxidation and lipid peroxidation was evident in all MDs and correlated with the severity of pathology, with DMD, the most severe dystrophic condition showing maximum damage, followed by Sgpy and Dysfy. Oxidative damage in DMD and Sgpy was attributed to the depletion of glutathione (GSH) and lowered antioxidant activities while loss of GSH peroxidase and GSH-S-transferase activities was observed in Dysfy. Lower GSH level in DMD was due to lowered activity of gamma-glutamyl cysteine ligase, the rate limiting enzyme in GSH synthesis. Similar analysis in cardiotoxin (CTX) mouse model of MD showed that the dystrophic muscle pathology correlated with GSH depletion and lipid peroxidation. Depletion of GSH prior to CTX exposure in C2C12 myoblasts exacerbated oxidative damage and myotoxicity. We deduce that the pro and anti-oxidant mechanisms could be correlated to the severity of MD and might influence the dystrophic pathology to a different extent in various MDs. On a therapeutic note, this could help in evolving novel therapies that offer myoprotection in MD.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

Oxidative Damage in Muscular Dystrophy Correlates with the Severity of the Pathology: Role of Glutathione Metabolism

et al. 2012

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“…Lipid peroxidation is a common index of free radical mediated injury (Halliwell and Gutteridge, 1989). Previous measurements of lipid peroxidation in dystrophin-deficient muscles have indicated elevated levels in both humans and mice (Kar and Pearson, 1979;Jackson et al, 1984;Mechler et al, 1984;Ragusa et al, 1997). A number of studies reported the reduction of oxidative stress by various mechanistic approaches, like antioxidant supplementation, led to a reduction in the adverse events in different pathologies (Grounds and Torrisi, 2004;Buck and Chojkier, 1996;Aragno et al, 2002;Buetler et al, 2002;Kaczor et al, 2007).…”

Section: Introductionmentioning

confidence: 96%

Histological assessment of SJL/J mice treated with the antioxidants coenzyme Q10 and resveratrol

Potgieter

Pretorius

Merwe

et al. 2011

Micron

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“…47 Oxidative stress in the dystrophic muscles of mdx mice is counteracted by compensatory mechanisms involving up-regulation of glutathione cycle enzymes. 27,45,48 We now show a similar adaptation of glutathione cycle enzymes expression in the heart of mdx mice, together with increased systemic glutathione reserve from the age of 15 weeks, when mice undergo a continuing cycle of skeletal muscle fiber degeneration and regeneration. 34,49 Such adaptive changes of glutathione metabolism in mdx mice are likely to lessen the severity and/or delay the progression of dystrophic disease and cardiomyopathy.…”

Section: Discussionmentioning

confidence: 74%

Delayed Cardiomyopathy in Dystrophin Deficient mdx Mice Relies on Intrinsic Glutathione Resource

Khouzami

Bourin

Christov

et al. 2010

The American Journal of Pathology

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Oxidative stress contributes to the pathogenesis of Duchenne muscular dystrophy (DMD). Although they have been a model for DMD, mdx mice exhibit slowly developing cardiomyopathy. We hypothesized that disease process was delayed owing to the development of an adaptive mechanism against oxidative stress, involving glutathione synthesis. At 15 to 20 weeks of age, mdx mice displayed a 33% increase in blood glutathione levels compared with age-matched C57BL/6 mice. In contrast, cardiac glutathione content was similar in mdx and C57BL/6 mice as a result of the balanced increased expression of glutamate cysteine ligase catalytic and regulatory subunits ensuring glutathione synthesis in the mdx mouse heart, as well as increased glutathione peroxidase-1 using glutathione. Oral administration from 10 weeks of age of the glutamate cysteine ligase inhibitor, L-buthionine(S,R)-sulfoximine (BSO, 5 mmol/L), led to a 33% and 50% drop in blood and cardiac glutathione, respectively, in 15-to 20-week-old mdx mice. Moreover, 20-week-old BSO-treated mdx mice displayed left ventricular hypertrophy associated with diastolic dysfunction, discontinuities in ␤-dystroglycan expression, micronecrosis and microangiopathic injuries. Examination of the glutathione status in four DMD patients showed that three displayed systemic glutathione deficiency as well. In conclusion, low glutathione resource hastens the onset of cardiomyopathy linked to a defect in dystrophin in mdx mice. This is relevant to the glutathione deficiency that DMD patients may suffer.

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Catalase, superoxide dismutase, glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle

Cited by 100 publications

References 19 publications

Oxidative Damage in Muscular Dystrophy Correlates with the Severity of the Pathology: Role of Glutathione Metabolism

Oxidative Damage in Muscular Dystrophy Correlates with the Severity of the Pathology: Role of Glutathione Metabolism

Histological assessment of SJL/J mice treated with the antioxidants coenzyme Q10 and resveratrol

Delayed Cardiomyopathy in Dystrophin Deficient mdx Mice Relies on Intrinsic Glutathione Resource

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