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Caloric restriction attenuates C57BL/6?J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure.

ABSTRACT: BACKGROUND:Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined. RESULTS:Male C57BL/6?J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4?weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77??g/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay. CONCLUSION:These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

SUBMITTER: Li D

PROVIDER: S-EPMC7275546 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure.

Li Daochuan D Chen Shen S Li Qiong Q Chen Liping L Zhang Haiyan H Li Huiyao H Yu Dianke D Zhang Rong R Niu Yujie Y Lu Shaoyou S Ye Lizhu L Zeng Xiaowen X Dong Guanghui G Chen Rui R Aschner Michael M Zheng Yuxin Y Chen Wen W

Particle and fibre toxicology 20200605 1

<h4>Background</h4>Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.<h4>Results</h4>Male C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m<sup>3</sup>) of PM<sub>2 ...[more]

PMID: 32503629

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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression

Project description:BackgroundFetal growth has been known to be associated with particulate matter (PM) air pollution during gestation. Given that regular working may deviate outdoor air pollution exposure, the association between air pollution and fetal growth restriction can be different across maternal working status. This study was to assess possible effect modification by maternal employment in the association between exposure to PM during pregnancy and fetal growth restriction.MethodsUsing hourly PM less than or equal to 10 and 2.5??m in diameter (PM10 and PM2.5) regulatory monitoring data for 2001-2012 and 2008-2012, respectively, and birth certificate data for 2002-2012, we computed maternal exposures with district-level averages of PM10 and PM2.5 during one year before birth, entire pregnancy, and the 1st, 2nd and 3rd trimesters. The outcomes of fetal growth restriction were assessed by small for gestational age (SGA, weighted <10th percentile in the same gestational age) as well as low birth weight (LBW, <?2.5?kg) at term. We performed logistic regression to examine the association between PM and each of fetal growth restriction outcomes adjusting for individual risk factors. For effect modification by maternal employment, we estimated adjusted odds ratio (OR) of SGA or LBW for interquartile (IQR) increases in PM10 or PM2.5 stratified by employed and non-employed mothers. We also computed relative excess risk due to interaction (RERI) to investigate additive interaction.ResultsAmong 824,011 singleton term births, 34.0% (279,856) were employed and 66.0% (544,155) were non-employed mothers. Proportions of LBW were 1.5% in employed and 1.6% in non-employed (P <?0.001). SGA occurred in 12.7% of employed and 12.8% of non- employed (P =?0.124) mothers. For non-employed mothers, we observed increased odds of SGA per IQR increase in PM10 for one year before birth (OR?=?1.02, 95% confidence intervals (CI): 1.00-1.04, P =?0.028). ORs of SGA for full pregnancy period and the 3rd trimester were also positive but did not reach statistical significance. We did not observe positive association for PM2.5. RERI was not significant both for PM10 and PM2.5.ConclusionsWe did not observe evidence of effect modification by maternal employment in the association between ambient PM and fetal growth restriction. Future studies using more refined exposure measures should confirm this finding.

Dataset Information

Caloric restriction attenuates C57BL/6?J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure.

Publications

Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure.

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