TY - JOUR
T1 - Illuminating a time-response mechanism in mice liver after PM2.5 exposure using metabolomics analysis
AU - Wang, Rongrong
AU - Han, Xi
AU - Pang, Huanhuan
AU - Hu, Zeping
AU - Shi, Chunzhen
N1 - Funding Information:
This work was financially supported by Support Project of High-level Teacher in Beijing Municipal Universities in the Period of 13th Five-year Plan (CIT&TCD201904032), National Natural Science Foundation of China ( 21407006 ).
Funding Information:
This work was financially supported by Support Project of High-level Teacher in Beijing Municipal Universities in the Period of 13th Five-year Plan (CIT&TCD201904032), National Natural Science Foundation of China (21407006).
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - PM2.5 is recognized as an atmospheric pollutant that seriously jeopardizes human health. Emerging evidence indicates that PM2.5 exposure is associated with metabolic disorders. Existing epidemiology and toxicology studies on the health effects of PM2.5 usually focused on its different components and doses, the effects on susceptible populations, or the effects of indoor and outdoor pollution. The underlying mechanisms of exposure time are poorly understood. Liver, as the central organ involved in various metabolisms, has special signaling pathways non-existed in lung and cardiovascular systems. Exacerbation in liver by the prolonged exposure of PM2.5 leads to hepatic function disorder. It is therefore essential to elucidate the mechanism underlying hepatotoxicity after PM2.5 exposure from the perspective of time-response relationship. In this study, targeted metabolomics was utilized to explore the hepatic injury in mice after PM2.5 exposure. Our results showed that prolonged exposure of PM2.5 would aggravate liver metabolic disorders. The metabolic process was divided into three phases. In phase I, it was found that PM2.5 exposure disturbed the hepatic urea synthesis. In phase II, oxidative damages and inflammations obviously occurred in liver, which would further cause neurobehavioral disorders and fat deposits. In phase III, the changes of metabolites and metabolic pathways indicated that the liver has been severely damaged, with the accelerated biosynthesis and fat metabolism. Finally, using ROC analysis coupled with their biological functions, 4 potential biomarkers were screened out, with which we established a method to classify and diagnose the progress of liver damage in mice after PM2.5 exposure. In this paper, we not only established the time-response relationship of PM2.5, but also provided new insights for the classification and prediction of the toxic injury stages in mice liver, which provides a ground work for the future drug intervention to prevent oxidative damage of PM2.5.
AB - PM2.5 is recognized as an atmospheric pollutant that seriously jeopardizes human health. Emerging evidence indicates that PM2.5 exposure is associated with metabolic disorders. Existing epidemiology and toxicology studies on the health effects of PM2.5 usually focused on its different components and doses, the effects on susceptible populations, or the effects of indoor and outdoor pollution. The underlying mechanisms of exposure time are poorly understood. Liver, as the central organ involved in various metabolisms, has special signaling pathways non-existed in lung and cardiovascular systems. Exacerbation in liver by the prolonged exposure of PM2.5 leads to hepatic function disorder. It is therefore essential to elucidate the mechanism underlying hepatotoxicity after PM2.5 exposure from the perspective of time-response relationship. In this study, targeted metabolomics was utilized to explore the hepatic injury in mice after PM2.5 exposure. Our results showed that prolonged exposure of PM2.5 would aggravate liver metabolic disorders. The metabolic process was divided into three phases. In phase I, it was found that PM2.5 exposure disturbed the hepatic urea synthesis. In phase II, oxidative damages and inflammations obviously occurred in liver, which would further cause neurobehavioral disorders and fat deposits. In phase III, the changes of metabolites and metabolic pathways indicated that the liver has been severely damaged, with the accelerated biosynthesis and fat metabolism. Finally, using ROC analysis coupled with their biological functions, 4 potential biomarkers were screened out, with which we established a method to classify and diagnose the progress of liver damage in mice after PM2.5 exposure. In this paper, we not only established the time-response relationship of PM2.5, but also provided new insights for the classification and prediction of the toxic injury stages in mice liver, which provides a ground work for the future drug intervention to prevent oxidative damage of PM2.5.
KW - Fine particulate matter
KW - Liver
KW - Metabolomics
KW - Time-response
UR - http://www.scopus.com/inward/record.url?scp=85098955362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098955362&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2020.144485
DO - 10.1016/j.scitotenv.2020.144485
M3 - Article
C2 - 33429275
AN - SCOPUS:85098955362
SN - 0048-9697
VL - 767
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 144485
ER -