Effects of repeated ozone exposure on pulmonary function and bronchial responsiveness in mice sensitized with ovalbumin

Funabashi, Hidemitsu; Shima, Masayuki; Kuwaki, Tomoyuki; Hiroshima, Kenzo; Kuriyama, Takayuki

doi:10.1016/j.tox.2004.06.047

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…For atherosclerotic lesion assessment, apoEϪ/Ϫ mice were exposed to 0.5 ppm O3 or FA from 6 to 14 wk of age, 5 days/wk, 8 h/day (12 a.m. to 8 a.m.). This concentration is substantially lower than levels used in several previous studies (e.g., 1.0 -2.5 ppm) (15,27), and although still higher than both EPA National Ambient Air Quality Standard (NAAQS) (0.075 ppm) and OSHA permissible exposure limit (0.1 ppm) regulatory levels, mice are routinely recognized as less susceptible to O3 insult than humans due to obligatory nose breathing and other intrinsic factors (42). Thus, the employed exposure paradigm represents an approach useful for delineating potential pathobiological sequelae in humans.…”

Section: Methodsmentioning

confidence: 70%

Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

Chuang

Yang²,

Westbrook³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

122

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More than 100 million people in the United States live in areas that exceed current ozone air quality standards. In addition to its known pulmonary effects, environmental ozone exposures have been associated with increased hospital admissions related to cardiovascular events, but to date, no studies have elucidated the potential molecular mechanisms that may account for exposure-related vascular impacts. Because of the known pulmonary redox and immune biology stemming from ozone exposure, we hypothesized that ozone inhalation would initiate oxidant stress, mitochondrial damage, and dysfunction within the vasculature. Accordingly, these factors were quantified in mice consequent to a cyclic, intermittent pattern of ozone or filtered air control exposure. Ozone significantly modulated vascular tone regulation and increased oxidant stress and mitochondrial DNA damage (mtDNA), which was accompanied by significantly decreased vascular endothelial nitric oxide synthase protein and indices of nitric oxide production. To examine influences on atherosclerotic lesion formation, apoE-/- mice were exposed as above, and aortic plaques were quantified. Exposure resulted in significantly increased atherogenesis compared with filtered air controls. Vascular mitochondrial damage was additionally quantified in ozone- and filtered air-exposed infant macaque monkeys. These studies revealed that ozone increased vascular mtDNA damage in nonhuman primates in a fashion consistent with known atherosclerotic lesion susceptibility in humans. Consequently, inhaled ozone, in the absence of other environmental toxicants, promotes increased vascular dysfunction, oxidative stress, mitochondrial damage, and atherogenesis.

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Section: Methodsmentioning

confidence: 70%

Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

Chuang

Yang²,

Westbrook³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

122

View full text Add to dashboard Cite

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“…Using an asthmatic phenotype modeled by allergic sensitization of the respiratory tract, effects of O 3 on pulmonary function have been found to be augmented by allergic sensitization in infant rhesus monkeys (Fanucchi et al 2006; Joad et al 2006; Schelegle et al 2003), mice (Funabashi et al 2004), and rats (Wagner et al 2007). In addition, in a bleomycin-induced pulmonary fibrosis rat model, exposure to O 3 increased pulmonary inflammation and fibrosis, along with the frequency of bronchopneumonia (Oyarzún et al 2005).…”

Section: Resultsmentioning

confidence: 99%

Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

Vinikoor-Imler

Owens

Nichols

et al. 2014

Environ Health Perspect

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Background: Epidemiologic and experimental studies have reported a variety of health effects in response to ozone (O3) exposure, and some have indicated that certain populations may be at increased or decreased risk of O3-related health effects.Objectives: We sought to identify potential response-modifying factors to determine whether specific groups of the population or life stages are at increased or decreased risk of O3-related health effects using a weight-of-evidence approach.Methods: Epidemiologic, experimental, and exposure science studies of potential factors that may modify the relationship between O3 and health effects were identified in U.S. Environmental Protection Agency’s 2013 Integrated Science Assessment for Ozone and Related Photochemical Oxidants. Scientific evidence from studies that examined factors that may influence risk were integrated across disciplines to evaluate consistency, coherence, and biological plausibility of effects. The factors identified were then classified using a weight-of-evidence approach to conclude whether a specific factor modified the response of a population or life stage, resulting in an increased or decreased risk of O3-related health effects.Discussion: We found “adequate” evidence that populations with certain genotypes, preexisting asthma, or reduced intake of certain nutrients, as well as different life stages or outdoor workers, are at increased risk of O3-related health effects. In addition, we identified other factors (i.e., sex, socioeconomic status, and obesity) for which there was “suggestive” evidence that they may increase the risk of O3-related health effects.Conclusions: Using a weight-of-evidence approach, we identified a diverse group of factors that should be considered when characterizing the overall risk of health effects associated with exposures to ambient O3.Citation: Vinikoor-Imler LC, Owens EO, Nichols JL, Ross M, Brown JS, Sacks JD. 2014. Evaluating potential response-modifying factors for associations between ozone and health outcomes: a weight-of-evidence approach. Environ Health Perspect 122:1166–1176; http://dx.doi.org/10.1289/ehp.1307541

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“…Although there have been several similar mouse studies looking at the O 3 effects on the asthmatic inflammation [ 10 , 18 , 22 – 24 ], our work is unique in the animal protocol to mimic the real situation of O 3 -induced asthma exacerbation in human. It is worth to note that the concentration of O 3 used in this study (1.0 ppm) is relative higher than the atmosphere O 3 concentration (~0.01 ppm) for inducing a measurable biological response.…”

Section: Discussionmentioning

confidence: 99%

Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model

Bao

Yang

et al. 2017

Respir Res

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BackgroundExposure to ambient ozone (O3) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O3 to trigger asthma exacerbations are still unclear.MethodsAn ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O3 (OVA-O3 model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O3 model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant). Biological measurements were conducted including airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL), inflammation in the airway lumen and lung parenchyma, the phosphorylation of p38 MAPK and heat shock protein (HSP) 27 in the tracheal tissues, and the malondialdehyde (MDA) content and the glutathione peroxidase (GSH-Px) activity in lung tissues.ResultsIn OVA-allergic mice, O3 exposure deteriorated airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL) and pulmonary inflammation, accompanied by the increased oxidative stress in lung tissues and promoted p38 MAPK and HSP27 phosphorylation in tracheal tissues. Administration of SB239063 (a p38 MAPK inhibitor) on OVA-O3 model exclusively mitigated the Raw, the CL, and the BAL IL-13 content, while α-tocopherol (antioxidant) differentially reduced the BAL number of eosinophils and macrophages, the content of BAL hyaluronan, the peribronchial inflammation, as well as the mRNA expression of TNF-α and IL-5 in the lung tissues of OVA-O3 model. Administration of these two chemical inhibitors similarly inhibited the AHR, the BAL IFN-γ and IL-6 production, the perivascular lung inflammation and the lung IL-17 mRNA expression of OVA-O3 model. Interestingly, the combined treatment of both compounds together synergistically inhibited neutrophil counts in the BALF and CXCL-1 gene expression in the lung.ConclusionsO3 exposure during the OVA challenge process promoted exacerbation in asthma. Both p38 MAPK and oxidative stress were found to play a critical role in this process and simultaneous inhibition of these two pathways significantly reduced the O3-elicited detrimental effects on the asthma exacerbation.

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Effects of repeated ozone exposure on pulmonary function and bronchial responsiveness in mice sensitized with ovalbumin

Cited by 11 publications

References 29 publications

Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model

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