Effect of <i>N</i>-Acetylcysteine on Human Diaphragm Strength and Fatigability

Travaline, John M.; Sudarshan, S; Roy, Bruce; Cordova, Francis; Leyenson, Vadim; Criner, Gerard J.

doi:10.1164/ajrccm.156.5.96-09133

Cited by 97 publications

(76 citation statements)

References 13 publications

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“…NAC is an antioxidant that acts both as a free radical scavenger and as a source of cysteine for glutathione synthesis. During IRB, NAC delays fatigue (52), increases the time to respiratory arrest (47), decreases the delayed diaphragmatic injury (at 3 days after severe IRB) (23), restores diaphragmatic glutathione levels (47), and decreases intradiaphragmatic protein carbonyl formation (5). In our model NAC administration blunted protein carbonyl formation in the diaphragm, decreased IRB-induced cytokine upregulation, and in parallel decreased P38, ERK1/2, and NF-B/p65 subunit phosphorylation, suggesting that ROS is a stimulus for MAPKs and NF-B activation and hence cytokine production in response to IRB.…”

Section: Role Of Oxidative Stressmentioning

confidence: 99%

MAPKs and NF-κB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

Sigala

Zacharatos²,

Toumpanakis

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Inspiratory resistive breathing (IRB) induces cytokine expression in the diaphragm. The mechanism of this cytokine induction remains elusive. The roles of MAPKs and NF-κB and the impact of oxidative stress in IRB-induced cytokine upregulation in the diaphragm were studied. Wistar rats were subjected to IRB (50% of maximal inspiratory pressure) via a two-way nonrebreathing valve for 1, 3, or 6 h. Additional groups of rats subjected to IRB for 6 h were randomly assigned to receive either solvent or N-acetyl-cysteine (NAC) or inhibitors of NF-κB (BAY-11–7082), ERK1/2 (PD98059), and P38 MAPK (SB203580) to study the effect of oxidative stress, NF-κB, and MAPKs in IRB-induced cytokine upregulation in the diaphragm. Quietly breathing animals served as controls. IRB upregulated cytokine (IL-6, TNF-α, IL-10, IL-2, IL-1β) protein levels in the diaphragm and resulted in increased activation of MAPKs (P38, ERK1/2) and NF-κB. Inhibition of NF-κB and ERK1/2 blunted the upregulation of all cytokines except that of IL-6, which was further increased. P38 inhibition attenuated all cytokine (including IL-6) upregulation. Both P38 and ERK1/2 inhibition decreased NF-κB/p65 subunit phosphorylation. NAC pretreatment blunted IRB-induced cytokine upregulation in the diaphragm and resulted in decreased ERK1/2, P38, and NF-κB/p65 phosphorylation. In conclusion, IRB-induced cytokine upregulation in the diaphragm is under the regulatory control of MAPKs and NF-κB. IL-6 is regulated differently from all other cytokines through a P38-dependent and NF-κB independent pathway. Oxidative stress is a stimulus for IRB-induced cytokine upregulation in the diaphragm.

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Section: Role Of Oxidative Stressmentioning

confidence: 99%

MAPKs and NF-κB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

Sigala

Zacharatos²,

Toumpanakis

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This effect was evident after 3 min of repetitive contractions and persisted throughout the 30-min protocol. Furthermore, TRAVALINE et al [92] showed that pre-administration of intravenous NAC may attenuate the development of fatigue and significantly increase diaphragm endurance in healthy subjects breathing against high inspiratory loads. Taken together, these data provide Reproduced from [35].…”

Section: After Exercisementioning

confidence: 99%

From muscle disuse to myopathy in COPD: potential contribution of oxidative stress

Couillard

Préfaut²

2005

European Respiratory Journal

160

125

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Evidence has been accumulating that chronic inactivity leading to muscle disuse is unlikely to be the only explanation for the peripheral muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients.Although a new concept of myopathy was recently proposed, the question of disuse and/or a form of myopathy is still being debated. This review proposes definitions for the terms used in this debate, discusses the relevant studies and concludes that the evidence points to a myopathy associated with muscle disuse in COPD.COPD myopathy implies pharmacological and/or pathophysiological mechanisms that need to be identified in order to optimally orient therapeutic strategies. The literature indicates that corticosteroids, inflammation, hypoxaemia and oxidative stress are among the factors contributing to COPD muscle dysfunction, but their relative contributions have not been fully elucidated.This review presents the advances in understanding each of these mechanisms, especially the data showing that muscle oxidative stress occurs and contributes to muscle dysfunction in chronic obstructive pulmonary disease. The current review also reports the studies that have elucidated the molecular mechanisms underlying this stress in chronic obstructive pulmonary disease by demonstrating alterations in oxidant and/or antioxidant systems. Finally, the review considers how inflammation and hypoxaemia may trigger oxidative stress in chronic obstructive pulmonary disease muscles and presents the therapeutic modalities that should be proposed to prevent it.

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“…13,17 For example, free radical scavengers N-acetylcysteine and aminophylline have been shown to attenuate diaphragm fatigue. [18][19][20] Research has shown that mitochondria stimulates the release of oxidants from the cells. [21][22][23] These oxidants may activate various apoptotic pathways.…”

mentioning

confidence: 99%

Dopamine alleviation of diaphragm contractile dysfunction and reduction of deoxyribonucleic acid damage in rats

et al. 2008

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Effect of N-Acetylcysteine on Human Diaphragm Strength and Fatigability

Cited by 97 publications

References 13 publications

MAPKs and NF-κB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

MAPKs and NF-κB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

From muscle disuse to myopathy in COPD: potential contribution of oxidative stress

Dopamine alleviation of diaphragm contractile dysfunction and reduction of deoxyribonucleic acid damage in rats

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