Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading

Domínguez-Álvarez, Marisol; Sabaté‐Brescó, Marina; Vilà-Ubach, Mònica; Gáldiz, Juan B.; Álvarez, Francisco J.; Casadevall, Carme; Gea, Joaquim; Barreiro, Esther

doi:10.1016/j.trsl.2013.12.004

Cited by 6 publications

(28 citation statements)

References 54 publications

(92 reference statements)

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“…Moreover, mitochondria was the most relevant contributor to oxidant production as levels were larger than in the other cell compartments and were, indeed, increased in both respiratory and limb muscles of the CIH‐exposed animals. These results are in agreement with former investigations, in which increased oxidant production was also shown in the muscles of COPD patients with severe hypoxia (Koechlin et al, ), in diaphragm of rats exposed to high‐inspiratory loading (Dominguez‐Alvarez et al, ), and in both respiratory and limb muscles of mice exposed to very short IH (Giordano et al, ). Systemic levels of superoxide anion were also significantly greater in the animals exposed to CIH compared to non‐exposed control rats.…”

Section: Discussionsupporting

confidence: 93%

“…The activity of the respiratory muscle, as opposed to the limb muscle, most likely accounts for the differential expression profile of cytokines between the two muscles. In fact, previous investigations have also demonstrated a rise in inflammatory cytokines only in the respiratory muscle following resistive breathing (Vassilakopoulos et al, ; Sigala et al, ) and high‐inspiratory threshold loading (Dominguez‐Alvarez et al, ) in rats.…”

Section: Discussionmentioning

confidence: 92%

“…The reagents used in these experiments were all purchased from Sigma (Sigma, Saint Louis, MO). Frozen muscle specimens from diaphragm and gastrocnemius of all groups were fractionated into cytosolic, membrane, and mitochondria compartments following previous reports by some of us (Marin‐Corral et al, ; Fermoselle et al, ; Dominguez‐Alvarez et al, ). The entire procedure was done at 4°C (on ice).…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the study period, differences in both physiological and biological variables (muscle and blood compartments) between the different study groups were assesed using one‐way analysis of variance, and Dunnett́s post‐hoc analysis was used to adjust for multiple comparisons. The sample size chosen was based on previous studies, where very similar approaches were employed (Barreiro et al, , ; Chacon‐Cabrera et al, ,; Dominguez‐Alvarez et al, ; Chacon‐Cabrera et al, ) and on assumptions of 80% power to detect an improvement of more than 20% in measured outcomes at a level of significance of P ≤ 0.05.…”

Section: Methodsmentioning

confidence: 99%

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Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies

Domínguez-Álvarez

Gea

Barreiro

2016

Journal Cellular Physiology

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We hypothesized that inflammatory events and reactive oxygen species (ROS) production may be differentially expressed in respiratory and limb muscles, and blood of a chronic intermittent hypoxia (CIH) experimental model and that antioxidants and TNF-alpha blockade may influence those events. In blood, diaphragm, and gastrocnemius of rats non-invasively exposed to CIH (10% hypoxia, 2 h/day, 14 consecutive days) with/without concomitant treatment with either anti-TNF-alpha antibody (infliximab) or N-acetyl cysteine (NAC), inflammatory cytokines, superoxide anion production, muscle structural abnormalities, and fiber-type composition were assessed. Compared to non-exposed controls, in CIH-exposed rats, body weight gain was reduced, TNF-alpha, IL-1beta, IL-6, and interferon-gamma levels were increased in diaphragm, TNF-alpha, and IL-1 beta plasma levels were greater, systemic and muscle superoxide anion production was higher, diaphragm and gastrocnemius inflammatory cells and internal nuclei were higher, and muscle fiber-type and morphometry remained unmodified. CIH rats treated with infliximab further increased TNF-alpha, IL-1beta, IL-6, and interferon-gamma diaphragm levels, whereas NAC induced a reduction only in TNF-alpha and IL-1beta levels in diaphragm and plasma. Infliximab and NAC elicited a significant decline in superoxide anion production in diaphragm, gastrocnemius, and plasma, while inducing a further increase in inflammatory cells and internal nuclei in both muscles. Proinflammatory cytokines are differentially expressed in respiratory and limb muscles and plasma of CIH-exposed rats, while superoxide anion production increased in both muscle types and blood. Infliximab and NAC exerted different effects. These findings may help understand the biology underlying CIH in skeletal muscles and blood of patients with chronic respiratory diseases. J. Cell. Physiol. 232: 1165-1175, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies

Domínguez-Álvarez

Gea

Barreiro

2016

Journal Cellular Physiology

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“…Non‐parametric Kruskal–Wallis test with a Mann–Whitney post hoc analysis was used to assess differences of the study biological variables between the experimental groups. The sample size chosen was based on previous studies, where very similar approaches were employed (Barreiro et al, , ; Fermoselle et al, ; Chacon‐Cabrera et al, ; Dominguez‐Alvarez et al, ), and on assumptions of 80% power to detect an improvement of >20% in measured outcomes at a level of significance of P ≤ 0.05.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure

et al. 2015

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Patients with chronic heart failure (CHF) experience exercise intolerance, fatigue and muscle wasting, which negatively influence their survival. We hypothesized that treatment with either the antioxidant N-acetyl cysteine (NAC) or the proteasome inhibitor bortezomib of rats with monocrotaline-induced CHF may restore inspiratory and limb muscle mass, function, and structure through several molecular mechanisms involved in protein breakdown and metabolism in the diaphragm and gastrocnemius. In these muscles of CHF-cachectic rats with and without treatment with NAC or bortezomib (N = 10/group) and non-cachectic controls, proteolysis (tyrosine release, proteasome activities, ubiquitin-proteasome markers), oxidative stress, inflammation, mitochondrial function, myosin, NF-κB transcriptional activity, muscle structural abnormalities, and fiber morphometry were analyzed together with muscle and cardiac functions. In diaphragm and gastrocnemius of CHF-cachectic rats, tyrosine release, proteasome activity, protein ubiquitination, atrogin-1, MURF-1, NF-κB activity, oxidative stress, inflammation, and structural abnormalities were increased, while muscle and cardiac functions, myosin content, slow- and fast-twitch fiber sizes, and mitochondrial activity were decreased. Concomitant treatment of CHF-cachectic rats with NAC or bortezomib improved protein catabolism, oxidative stress, inflammation, muscle fiber sizes, function and damage, superoxide dismutase and myosin levels, mitochondrial function (complex I, gastrocnemius), cardiac function and decreased NF-κB transcriptional activity in both muscles. Treatment of CHF-cachectic animals with NAC or bortezomib attenuated the functional (heart, muscles), biological, and structural alterations in muscles. Nonetheless, future studies conducted in actual clinical settings are warranted in order to assess the potential beneficial effects and safety concerns of these pharmacological agents on muscle mass loss and wasting in CHF-cachectic patients.

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Impact of drugs with anti-inflammatory effects on skeletal muscle and inflammation: A systematic literature review

Alturki

Beyer

Mets

et al. 2018

Experimental Gerontology

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Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading

Cited by 6 publications

References 54 publications

Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies

Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure

Impact of drugs with anti-inflammatory effects on skeletal muscle and inflammation: A systematic literature review

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