title: 1H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.
abstract: Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5by using a1H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using1H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5treated rats. The mainly affected metabolic pathways by PM2.5were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants.
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Hejing
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Lige
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Collins Otieno
authors.initials: CO
authors.lastname: Asweto
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China. Electronic address: jcduan@ccmu.edu.cn.
authors.forename: Junchao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069. PR China. Electronic address: zwsun@ccmu.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D007678:Kidney Glomerulus / Q000473:pathology; D008099:Liver / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D052638:Particulate Matter / Q000633:toxicity*; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests; D014132:Trachea
chemical_list: D052638:Particulate Matter
keywords: Fine particulate matter; Metabolites; Metabolomics; Pathway analysis; Rats; Toxicity