PMID- 31398419 OWN - NLM STAT- MEDLINE DCOM- 20191028 LR - 20191028 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 233 DP - 2019 Sep 15 TI - Lysosomal dysfunction is associated with persistent lung injury in dams caused by pregnancy exposure to carbon black nanoparticles. PG - 116741 LID - S0024-3205(19)30668-X [pii] LID - 10.1016/j.lfs.2019.116741 [doi] AB - AIMS: Carbon black nanoparticles (CBNPs) are widely used in industrial field. Sensitive stages such as pregnancy are assumed to be more susceptible to stimulus, however whether pregnancy exposure to CBNPs (PrE-to-CBNPs) would cause long-term toxic effects in dams and the underlying mechanisms remain poorly addressed. The present study is aimed to determine the long-term toxic effects of PrE-to-CBNPs in dams. MATERIALS AND METHODS: The pregnant mice were randomly divided into control group, low (21 mug/animal), medium (103 mug/animal) and high (515 mug/animal) CBNPs-treated groups. From gestational day (GD) 9 to GD18, the pregnant mice were intranasal exposed. At 49 days after parturition, lung tissues and bronchoalveolar lavage fluid (BALF) were obtained. Weight change, lung histopathology, lung ultrastructural pathology, cell count in BALF, oxidative stress/inflammatory maker and autophagy/lysosome-related protein expression were determined. KEY FINDINGS: PrE-to-CBNPs caused a dose-dependent persistent lung injury in mice even 49 days after parturition, including the deteriorative lung histopathological changes, elevation of oxidative stress marker Nrf-2, HO-1 and CHOP, infiltration of macrophage and increased mRNA expression of inflammatory cytokines in the lung tissues and elevation of cells in BALF. However, PrE-to-CBNPs did not induce significant neutrophil infiltration and fibrosis. Moreover, we found that CBNPs could deposit in the lysosomes and decrease cathepsin D (an important hydrolase in lysosome), which might be associated with the dysfunction of lysosome and autophagy. SIGNIFICANCE: Our study demonstrated that PrE-to-CBNPs could result in long-term lung injury in dams, and lysosomal dysfunction was probably linked to this process. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Liu, Xuemei AU - Liu X AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. FAU - Tu, Baijie AU - Tu B AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. FAU - Jiang, Xuejun AU - Jiang X AD - Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing 400016, PR China. FAU - Xu, Ge AU - Xu G AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, PR China. FAU - Bai, Lulu AU - Bai L AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. FAU - Zhang, Longbin AU - Zhang L AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. FAU - Meng, Pan AU - Meng P AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. FAU - Qin, Xia AU - Qin X AD - Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. FAU - Chen, Chengzhi AU - Chen C AD - Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China; Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: chengzhichen@cqmu.edu.cn. FAU - Zou, Zhen AU - Zou Z AD - Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, PR China; Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: zouzhen@cqmu.edu.cn. LA - eng PT - Journal Article DEP - 20190806 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Cytokines) RN - 0 (Soot) SB - IM MH - Animals MH - Autophagy MH - Cytokines/metabolism MH - Female MH - Inflammation/*complications MH - Lung Injury/*etiology/pathology MH - Lysosomes/*pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nanoparticles/*adverse effects MH - *Oxidative Stress MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*etiology/pathology MH - Soot/*adverse effects OTO - NOTNLM OT - Carbon black nanoparticles OT - Lysosomal dysfunction OT - Persistent lung injury OT - Pregnancy exposure EDAT- 2019/08/10 06:00 MHDA- 2019/10/29 06:00 CRDT- 2019/08/10 06:00 PHST- 2019/06/17 00:00 [received] PHST- 2019/07/31 00:00 [revised] PHST- 2019/08/06 00:00 [accepted] PHST- 2019/08/10 06:00 [pubmed] PHST- 2019/10/29 06:00 [medline] PHST- 2019/08/10 06:00 [entrez] AID - S0024-3205(19)30668-X [pii] AID - 10.1016/j.lfs.2019.116741 [doi] PST - ppublish SO - Life Sci. 2019 Sep 15;233:116741. doi: 10.1016/j.lfs.2019.116741. Epub 2019 Aug 6.