Xuemei Liu1, Baijie Tu1, Xuejun Jiang2, Ge Xu3, Lulu Bai1, Longbin Zhang1, Pan Meng1, Xia Qin4, Chengzhi Chen5, Zhen Zou6. 1. Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, PR China. 2. Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing 400016, PR China. 3. Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, PR China. 4. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. 5. 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. 6. 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.
Abstract
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 μg/animal), medium (103 μg/animal) and high (515 μg/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.
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 μg/animal), medium (103 μg/animal) and high (515 μg/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.