PMID- 32503629 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20240426 IS - 1743-8977 (Electronic) IS - 1743-8977 (Linking) VI - 17 IP - 1 DP - 2020 Jun 5 TI - Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure. PG - 22 LID - 10.1186/s12989-020-00354-2 [doi] LID - 22 AB - 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 mug/m(3)) of PM(2.5). 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. FAU - Li, Daochuan AU - Li D AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Chen, Shen AU - Chen S AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Li, Qiong AU - Li Q AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Chen, Liping AU - Chen L AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Zhang, Haiyan AU - Zhang H AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Li, Huiyao AU - Li H AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Yu, Dianke AU - Yu D AD - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 266021, China. FAU - Zhang, Rong AU - Zhang R AD - Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, China. FAU - Niu, Yujie AU - Niu Y AD - Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, China. FAU - Lu, Shaoyou AU - Lu S AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Ye, Lizhu AU - Ye L AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Zeng, Xiaowen AU - Zeng X AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Dong, Guanghui AU - Dong G AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. FAU - Chen, Rui AU - Chen R AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China. FAU - Aschner, Michael AU - Aschner M AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. FAU - Zheng, Yuxin AU - Zheng Y AD - Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 266021, China. FAU - Chen, Wen AU - Chen W AUID- ORCID: 0000-0001-5435-1664 AD - Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China. chenwen@mail.sysu.edu.cn. LA - eng GR - R01 ES007331/ES/NIEHS NIH HHS/United States GR - R01 ES07331/ES/NIEHS NIH HHS/United States GR - R01 ES10563/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200605 PL - England TA - Part Fibre Toxicol JT - Particle and fibre toxicology JID - 101236354 RN - 0 (Air Pollutants) RN - 0 (Particulate Matter) SB - IM MH - Air Pollutants/pharmacokinetics/*toxicity MH - Animals MH - *Caloric Restriction MH - Liver/drug effects/metabolism MH - Liver Function Tests MH - Lung/*drug effects/metabolism MH - Lung Injury/chemically induced/*prevention & control MH - Male MH - Mice, Inbred C57BL MH - Particle Size MH - Particulate Matter/pharmacokinetics/*toxicity PMC - PMC7275546 OTO - NOTNLM OT - Caloric restriction OT - Extra-pulmonary toxicity OT - Particulate matter OT - Pulmonary injury OT - RNA sequencing OT - Xenobiotic metabolism COIS- The authors declare they have no actual or potential competing financial interests. EDAT- 2020/06/07 06:00 MHDA- 2021/04/02 06:00 PMCR- 2020/06/05 CRDT- 2020/06/07 06:00 PHST- 2020/02/05 00:00 [received] PHST- 2020/05/26 00:00 [accepted] PHST- 2020/06/07 06:00 [entrez] PHST- 2020/06/07 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2020/06/05 00:00 [pmc-release] AID - 10.1186/s12989-020-00354-2 [pii] AID - 354 [pii] AID - 10.1186/s12989-020-00354-2 [doi] PST - epublish SO - Part Fibre Toxicol. 2020 Jun 5;17(1):22. doi: 10.1186/s12989-020-00354-2.