Modelling COPD co‐morbidities in preclinical models

Vlahos, Ross; Bozinovski, Steven

doi:10.1111/resp.13416

Cited by 8 publications

(10 citation statements)

References 8 publications

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“…One study available in the literature shows that the expression of Atrogin-1 in muscle cells and tubes of COPD patients is significantly higher than that in healthy individuals [44]. Another study demonstrates that COPD rats showing significantly reduced grip strength and aerobic exercise capacity also exhibit increased levels of E3 ligase proteins in their skeletal muscles [45]. Consistently, our results indicate that the expressions of Atrogin-1 and MuRF1 in the gastrocnemius of COPD rats are higher than those of control rats.…”

Section: Effect Of Smoke Exposure On the Skeletal Muscles Of Ratssupporting

confidence: 87%

The rat model of COPD skeletal muscle dysfunction induced by progressive cigarette smoke exposure: a pilot study

et al. 2020

BMC Pulm Med

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Background: Chronic obstructive pulmonary disease (COPD) skeletal muscle dysfunction is a prevalent malady that significantly affects patients' prognosis and quality of life. Although the study of this disease has attracted considerable attention, a definite animal model is yet to be established. This study investigates whether smoke exposure could lead to the development of a COPD skeletal muscle dysfunction model in rats. Methods: Sprague Dawley rats were randomly divided into model (MG, n = 8) and control groups (CG, n = 6). The MG was exposed to cigarette smoke for 16 weeks while the CG was not. The body weight and forelimb grip strength of rats were monitored monthly. The pulmonary function and the strength of tibialis anterior muscle were assessed in vitro and compared after establishing the model. The histological changes in lung and gastrocnemius muscles were observed. The expressions of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were detected by ELISA, while the expressions of Atrogin-1 and MuRF1 in the gastrocnemius muscle were determined by Western blotting. Results: Smoke exposure slowly increases the body weight and forelimb grip strength of MG rats, compared to CG rats. However, it significantly decreases the pulmonary ventilation function and the skeletal muscle contractility of the MG in vitro. Histologically, the lung tissues of MG show typical pathological manifestations of emphysema, while the skeletal muscles present muscular atrophy. The expressions of IL-6, IL-8, and TNF-α in MG rats are significantly higher than those measured in CG rats. Increased levels of Atrogin-1 and MuRF1 were also detected in the gastrocnemius muscle tissue of MG. Conclusion: Progressive smoking exposure decreases the contractile function of skeletal muscles, leading to muscular atrophy. It also increases the expressions of inflammatory and muscle protein degradation factors in COPD rats. This indicates that smoke exposure could be used to establish a COPD skeletal muscle dysfunction model in rats.

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Section: Effect Of Smoke Exposure On the Skeletal Muscles Of Ratssupporting

confidence: 87%

The rat model of COPD skeletal muscle dysfunction induced by progressive cigarette smoke exposure: a pilot study

et al. 2020

BMC Pulm Med

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“…This study investigated whether prior cigarette smoke exposure worsens brain injury and stroke outcomes (functional hanging wire test, neurological scoring, infarct and oedema volume) in mice. The cigarette smoke exposure protocols used in this study replicate many aspects of human COPD and have been used previously to investigate the molecular and biochemical mechanisms underlying the pathogenesis of COPD [ 26 , 34 ]. Briefly, the model involves exposing mice to CS over a period of days to months, depending on what features of cigarette smoke-induced lung inflammation and damage want to be modelled.…”

Section: Discussionmentioning

confidence: 99%

Prior cigarette smoke exposure does not affect acute post-stroke outcomes in mice

2019

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Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally and is characterized by airflow limitation that is progressive and not fully reversible. Cigarette smoking is the major cause of COPD. Fifty percent of deaths in the COPD population are due to a cardiovascular event and it is now recognised that COPD is a risk factor for stroke. Whether COPD increases stroke severity has not been explored. The aim of this study was to investigate whether functional and histological endpoints of stroke outcomes in mice after transient middle cerebral artery occlusion (tMCAo) were more severe in mice exposed to cigarette smoke (CS). 7-week-old male C57BL/6 mice were exposed to room air or CS generated from 9 cigarettes/day, 5 days/week for 2, 8 and 12 weeks. Following air or CS exposure, mice underwent tMCAO surgery with an ischaemic period of 30–40 min or sham surgery. Mice were euthanised 24 h following the induction of ischaemia and bronchoalveolar lavage fluid (BALF), lungs and brains collected. Mice exposed to CS for 2 weeks and subjected to a stroke had similar BALF macrophages to air-exposed and stroke mice. However, CS plus stroke mice had significantly more BALF total cells, neutrophils and lymphocytes than air plus stroke mice. Mice exposed to CS for 8 and 12 weeks had significantly greater BALF total cells, macrophages, neutrophils and lymphocytes than air-exposed mice, but stroke did not affect CS-induced BALF cellularity. Prior CS exposure did not worsen stroke-induced neurological deficit scores, reduced foregrip strength, infarct and oedema volumes. Collectively, we found that although CS exposure caused significant BALF inflammation, it did not worsen acute post-stroke outcomes in mice. This data suggests that while patients with COPD are at increased risk of stroke, it may not translate to COPD patients having more severe stroke outcomes.

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“…Animals began smoke exposure at a minimum of 6 cigarettes per day, with the total number of cigarettes increasing by 2 per day until reaching 24 total per day and then remaining constant for the remainder of the regimen. This regimen was selected to simulate acute-smoke-exposure models, which have been shown to induce significant inflammatory, genetic, and injury responses in the lung ( 38 – 40 , 69 , 70 ). Animals were monitored continuously during smoke exposure.…”

Section: Methodsmentioning

confidence: 99%

“…Analysis of sequenced NTHi genomes revealed a number of homologs of enzymes involved in reduction of oxidized thiols, including predicted glutathione reductase ( gor , NTHI0251), thioredoxin-dependent thiol peroxidase ( bcp , NTHI0361), thiol peroxidase ( tpx , NTHI0907), thioredoxin reductase ( trxB , NTHI1327) and glutaredoxin/peroxiredoxin ( pdgX , NTHI0705) ( Table 1 ) ( 38 – 40 ). We used a bacterial genetic approach to generate isogenic mutant strains with predicted impacts on thiol redox metabolism, which were then used to investigate the importance of this pathway in colonization, persistence, and biofilm formation within the airways.…”

Section: Introductionmentioning

confidence: 99%

Nontypeable Haemophilus influenzae Redox Recycling of Protein Thiols Promotes Resistance to Oxidative Killing and Bacterial Survival in Biofilms in a Smoke-Related Infection Model

Hunt

Gaggar

et al. 2022

mSphere

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Modelling COPD co‐morbidities in preclinical models

Cited by 8 publications

References 8 publications

The rat model of COPD skeletal muscle dysfunction induced by progressive cigarette smoke exposure: a pilot study

The rat model of COPD skeletal muscle dysfunction induced by progressive cigarette smoke exposure: a pilot study

Prior cigarette smoke exposure does not affect acute post-stroke outcomes in mice

Nontypeable Haemophilus influenzae Redox Recycling of Protein Thiols Promotes Resistance to Oxidative Killing and Bacterial Survival in Biofilms in a Smoke-Related Infection Model

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