Seawater inhalation induces acute lung injury via ROS generation and the endoplasmic reticulum stress pathway

Li,Peng‑Cheng; Wang,Bo‑Rong; Li,Cong‑Cong; Lu,Xi; Qian,Wei‑Sheng; Li,Yu‑Juan; Jin,Fa‑Guang; Mu,De‑Guang

doi:10.3892/ijmm.2018.3486

Seawater inhalation induces acute lung injury via ROS generation and the endoplasmic reticulum stress pathway

Authors:
- Peng‑Cheng Li
- Bo‑Rong Wang
- Cong‑Cong Li
- Xi Lu
- Wei‑Sheng Qian
- Yu‑Juan Li
- Fa‑Guang Jin
- De‑Guang Mu
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Affiliations: Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: February 12, 2018 https://doi.org/10.3892/ijmm.2018.3486
Pages: 2505-2516
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Seawater (SW) inhalation can induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, SW induced apoptosis of rat alveolar epithelial cells and histopathological alterations to lung tissue. Furthermore, SW administration increased generation of reactive oxygen species (ROS), whereas pretreatment with the ROS scavenger, N‑acetyl‑L‑cysteine (NAC), significantly decreased ROS generation, apoptosis and histopathological alterations. In addition, SW exposure upregulated the expression levels of glucose‑regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), which are critical proteins in the endoplasmic reticulum (ER) stress response, thus indicating that SW may activate ER stress. Conversely, blocking ER stress with 4‑phenylbutyric acid (4‑PBA) significantly improved SW‑induced apoptosis and histopathological alterations, whereas an ER stress inducer, thapsigargin, had the opposite effect. Furthermore, blocking ROS with NAC inhibited SW‑induced ER stress, as evidenced by the downregulation of GRP78, phosphorylated (p)‑protein kinase R‑like ER kinase (PERK), p‑inositol‑requiring kinase 1α (IRE1α), p‑50 activating transcription factor 6α and CHOP. In addition, blocking ER stress with 4‑PBA decreased ROS generation. In conclusion, the present study indicated that ROS and ER stress pathways, which are involved in alveolar epithelial cell apoptosis, are important in the pathogenesis of SW‑induced ALI.

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