Etomidate attenuates hyperoxia‑induced acute lung injury in mice by modulating the Nrf2/HO‑1 signaling pathway

Jia,Liming; Hao,Hongzhong; Wang,Chunyu; Wei,Jianfeng

doi:10.3892/etm.2021.10217

Etomidate attenuates hyperoxia‑induced acute lung injury in mice by modulating the Nrf2/HO‑1 signaling pathway

Authors:
- Liming Jia
- Hongzhong Hao
- Chunyu Wang
- Jianfeng Wei
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Affiliations: Department of Anesthesiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China
Published online on: May 19, 2021 https://doi.org/10.3892/etm.2021.10217
Article Number: 785
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the protective effects of etomidate on hyperoxia‑induced acute lung injury in mice, particularly on the nuclear factor‑erythroid 2‑related factor 2 (Nrf2)/heme oxygenase 1 (HO‑1) pathway. Fifty specific pathogen‑free mice were randomly divided into the blank control, model, high oxygen exposure + low etomidate dose (0.3 mg·kg‑1), a high oxygen exposure + moderate etomidate dose (3 mg·kg‑1), and a high oxygen exposure + high etomidate dose (10 mg·kg‑1) groups, with ten mice allotted per group. After 72 h, the mice were sacrificed and the lung tissues were harvested, and the wet‑to‑dry (W/D) ratio of the tissues was calculated. Hematoxylin‑eosin staining was performed to observe the pathological changes in the lung tissues, and the lung injury score (LIS) was calculated. The mRNA and protein expression levels of Nrf2 and HO‑1 were measured. The malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels were also measured, and interleukin (IL)‑1β, IL‑6, tumor necrosis factor alpha (TNF‑α) and IL‑10 concentrations in the bronchoalveolar lavage fluid were determined. At low and moderate doses, etomidate decreased pathological damage in the lung tissue, decreased the LIS and W/D ratio, upregulated Nrf2 and HO‑1 mRNA and protein expression, decreased IL‑1β, IL‑6, and TNF‑α concentrations, increased MPO activity and IL‑10 levels, suppressed the production of the oxidation product MDA, and enhanced the activities of the antioxidant enzymes CAT and SOD. Within a certain dose range, etomidate enhanced antioxidant and anti‑inflammatory effects in mice, thereby decreasing lung injury induced by the chronic inhalation of oxygen at high concentrations. Furthermore, the underlying mechanism may be associate with the upregulation of the Nrf2/HO‑1 signaling pathway.

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