1. Academic Validation
  2. Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis

Ferroptosis participated in inhaled polystyrene nanoplastics-induced liver injury and fibrosis

  • Sci Total Environ. 2024 Jan 24:916:170342. doi: 10.1016/j.scitotenv.2024.170342.
Yiling Ge 1 Sheng Yang 1 Tianyi Zhang 1 Saisai Gong 1 Xin Wan 1 Yuxin Zhu 1 Yifei Fang 1 Chengyu Hu 1 Fei Yang 2 Lihong Yin 1 Yuepu Pu 1 Zaozao Chen 3 Geyu Liang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, PR China.
  • 2 Department of Epidemiology and Health Statistics, The Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Public Health, Hengyang Medical School, University of South China, PR China.
  • 3 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, PR China. Electronic address: 101012282@seu.edu.cn.
  • 4 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, PR China. Electronic address: lianggeyu@163.com.
Abstract

The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs-induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS-NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 μg/day). Results showed that inhaled PS-NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time-dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-β, α-SMA, and Col1a1 identified that inhaled PS-NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that Ferroptosis was involved in PS-NPs-induced liver hepatotoxicity, and key features of Ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that Ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of Ferroptosis in PS-NPs-induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS-NPs on the liver, identified that continuous inhaled PS-NPs could cause liver injury and fibrosis, and PS-NPs- Ferroptosis provided a novel mechanistic explanation.

Keywords

AOP framework; Ferroptosis; Inhalation exposure; Liver injury and fibrosis; Nanoplastics.

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