Cardiac dysfunction subsequent to chronic ozone exposure in rats

Perepu, Rama Surya Prakash; Dostal, David E.; García, Carlos; Kennedy, Richard H.; Sethi, Rajat

doi:10.1007/s11010-011-1073-1

Cited by 18 publications

(2 citation statements)

References 24 publications

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“…O 3 is a strong oxidant, and, although not a radical species, most of its toxic effects are mediated through free radical reactions (21,22). Oxidative stress is indeed implicated in many deleterious effects of O 3 , such as pulmonary inflammation and dysfunction (23), Alzheimer's disease (24), and cardiovascular diseases (25). In a recent study, Bass et al (26) demonstrated that O 3 impaired glucose homeostasis in rats; however, very little is known about the effects of O 3 on metabolism and metabolic diseases.…”

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confidence: 99%

Ozone Exposure Triggers Insulin Resistance Through Muscle c-Jun N-Terminal Kinase Activation

et al. 2014

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A growing body of evidence suggests that exposure to traffic-related air pollution is a risk factor for type 2 diabetes. Ozone, a major photochemical pollutant in urban areas, is negatively associated with fasting glucose and insulin levels, but most aspects of this association remain to be elucidated. Using an environmentally realistic concentration (0.8 parts per million), we demonstrated that exposure of rats to ozone induced whole-body insulin resistance and oxidative stress, with associated endoplasmic reticulum (ER) stress, c-Jun N-terminal kinase (JNK) activation, and disruption of insulin signaling in skeletal muscle. Bronchoalveolar lavage fluids from ozone-treated rats reproduced this effect in C2C12 myotubes, suggesting that toxic lung mediators were responsible for the phenotype. Pretreatment with the chemical chaperone 4-phenylbutyric acid, the JNK inhibitor SP600125, or the antioxidant N-acetylcysteine alleviated insulin resistance, demonstrating that ozone sequentially triggered oxidative stress, ER stress, and JNK activation to impair insulin signaling in muscle. This study is the first to report that ozone plays a causative role in the development of insulin resistance, suggesting that it could boost the development of diabetes. We therefore provide a potential mechanism linking pollutant exposure and the increased incidence of metabolic diseases.

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confidence: 99%

Ozone Exposure Triggers Insulin Resistance Through Muscle c-Jun N-Terminal Kinase Activation

et al. 2014

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“…A recent report by Perepu et al (2012) showed the chronic effects of O 3 exposure (8 h/day at 0.8 ppm for 28 or 56 days) on cardiac dysfunction in rats. Altered function induced by O 3 included significant decrements in LV dP/dt max and dP/dt min as well as elevated LVEDP.…”

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confidence: 99%

Effects of Ozone and Particulate Matter on Cardiac Mechanics: Role of the Atrial Natriuretic Peptide Gene

Tankersley¹,

Georgakopoulos²,

Tang³

et al. 2012

Toxicological Sciences

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A positive association between air pollution exposure and increased human risk of chronic heart disease progression is well established. In the current study, we test two hypotheses: (1) the cardiac compensatory changes in response to air pollution are dependent on its composition and (2) specific cardiac adaptations are regulated by atrial natriuretic peptide (ANP). We address these hypotheses by initially examining the exposure effects of ozone (O(3)) and/or particulate matter (PM) on cardiac function in C57Bl/6J (B6) mice. Subsequently, the results are compared with cardiac functional changes to the same exposures in Nppa (the precursor gene for ANP) knockout (KO) mice. Separate groups of mice underwent 3 consecutive days of the same exposure sequence for 3h each consisting of the following: (1) 6h of filtered air (FAFA), (2) O(3) then FA (O(3)FA), (3) FA then carbon black (FACB), or (4) O(3) then CB. Cardiac function was assessed using a conductance catheter to generate cardiac pressure-volume loops 8-10h following each exposure sequence. As compared with FAFA, each sequence led to a substantial drop (as much as 33%) in stroke volume and cardiac output. However, these losses of cardiac function occurred by different compensatory mechanisms dependent on the pollutant composition. For example, O(3)FA exposure led to reductions in both end-systolic and end-diastolic left ventricular (LV) volumes, whereas FACB exposure led an increase in end-diastolic LV volume. These same cardiac compensatory changes were largely abolished in Nppa KO mice following O(3)FA or FACB exposure. These results suggest that cardiac functional changes in response to air pollution exposure are strongly dependent on the pollutant constituents, especially related to O(3) and/or PM. Furthermore, ANP regulation appears to be crucial to these cardiac compensatory mechanisms induced by air pollution.

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Differential expression of caveolin-1 and caveolin-3: potential marker for cardiac toxicity subsequent to chronic ozone inhalation

et al. 2012

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Earlier studies from our laboratory have shown myocardial dysfunction subsequent to chronic O(3) exposure in rats may be associated with a decrease in antioxidant reserve and increased activity of inflammatory mediators. The present study tested the hypothesis that O(3)-induced cardiac dysfunction in healthy adult rats may be due to changes in caveolin-1 and caveolin-3 levels. Sprague-Dawley rats were exposed 8 h/day for 28 and 56 days to filtered air or 0.8 ppm O(3). In order to assess the chronic effects to O(3), in vivo cardiac function was assessed by measuring LVDP, 24 h after termination of O(3) exposure. Compared to rats exposed to filtered air, LVDP values significantly decreased in all O(3)-exposed animals. This attenuation of cardiac function was associated with increased myocardial TNF-α levels and decreased myocardial activities of superoxidase dismutase. Progressive increases in the expression of myocardial TNF-α in 28 days and 56 days O(3)-exposed animals were followed by decreases in cardiac caveolin-1 levels. On the other hand, differential changes in the expression of caveolin-3 in hearts from 28 and 56 days O(3)-exposed animals were independent of intra-cardiac TNF-α levels. These novel findings suggest the interesting possibility that a balance between caveolin-1 and caveolin-3 may be involved in O(3)-mediated cardiac toxicity.

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Cardiac dysfunction subsequent to chronic ozone exposure in rats

Cited by 18 publications

References 24 publications

Ozone Exposure Triggers Insulin Resistance Through Muscle c-Jun N-Terminal Kinase Activation

Ozone Exposure Triggers Insulin Resistance Through Muscle c-Jun N-Terminal Kinase Activation

Effects of Ozone and Particulate Matter on Cardiac Mechanics: Role of the Atrial Natriuretic Peptide Gene

Differential expression of caveolin-1 and caveolin-3: potential marker for cardiac toxicity subsequent to chronic ozone inhalation

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