title: Comprehensive pulmonary metabolome responses to intratracheal instillation of airborne fine particulate matter in rats.
abstract: Airborne fine particulate matter (PM2.5) has been closely related with a variety of lung diseases. Although some modes of action (e.g. oxidative stress, inflammations) have been proposed, but the pulmonary toxicological mechanism remains obscure. In this paper, in order to understand the comprehensive pulmonary response to PM2.5 stress, a non-targeted high-throughput metabolomics strategy was adopted to characterize the overall metabolic changes and relevant toxicological pathways. PM2.5 samples were collected from Tangshan, one of the most polluted cities in China. Adult male rats were treated with PM2.5 suspension once a week at the dose of 1mg/kg/week through intratracheal instillation in three months. Aqueous and organic metabolite extracts of the lung tissues were subjected to metabolomics analysis using ultra-high performance liquid chromatograph/mass spectrometry. Along with a significant increase of oxidative stress, significant metabolome alterations were observed in the lung tissues of the treated rats. Nineteen metabolites were found decreased and 31 metabolites increased, which are mainly involved in lipid and nucleotide metabolism. Integrated pathway analysis suggests that PM2.5 can induce pulmonary toxicity through disturbing pro-oxidant/antioxidant balance, which may further correlate with metabolism changes of phospholipid, glycerophospholipid, sphingolipid and purine. These findings improve our understanding of the toxicological pathways of PM2.5 exposure.
authors.affiliation: Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China.
authors.forename: Shoufang
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Du
authors.affiliation: Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China. Electronic address: weibingzhang@ecust.edu.cn.
authors.forename: Weibing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China. Electronic address: jzhang@iue.ac.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D002681:China; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D010316:Particle Size; D052638:Particulate Matter / Q000009:adverse effects*; D051381:Rats
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Fine particulate matter; Lipid metabolism; Pulmonary toxicity; Purine metabolism