Dexmedetomidine attenuates airway inflammation and oxidative stress in asthma via the Nrf2 signaling pathway

Xiao,Shilin; Zhou,Ying; Gao,Huibin; Yang,Dong

doi:10.3892/mmr.2022.12889

Dexmedetomidine attenuates airway inflammation and oxidative stress in asthma via the Nrf2 signaling pathway

Authors:
- Shilin Xiao
- Ying Zhou
- Huibin Gao
- Dong Yang
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Affiliations: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
Published online on: November 2, 2022 https://doi.org/10.3892/mmr.2022.12889
Article Number: 2
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Allergic asthma is a chronic inflammatory disease in which oxidative stress serves a pivotal role. In clinical practice, dexmedetomidine (DEX), an α‑2‑adrenergic receptor agonist, is used as a sedative. DEX exhibits antioxidative and organ‑protective properties. In a murine model of asthma, DEX has a therapeutic effect via the toll like receptor 4/NF‑кB signaling pathway; however, whether DEX can exert an antioxidative effect on asthma has yet to be elucidated. In the present study, a T helper (Th)2‑dominant murine asthma model was established. DEX treatment significantly reduced eosinophilic airway inflammation, mucus overproduction and airway hyperresponsiveness, as well as the concentrations of Th2 cytokines. The lung tissues of mice with asthma were characterized by redox imbalance (increased oxidative stress and impaired antioxidant capacity). DEX treatment alleviated this imbalance by decreasing the levels of malondialdehyde and reactive oxygen species, and increasing the levels of glutathione. Furthermore, the nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway was inhibited in the lung tissues of asthmatic mice; these effects were noted in its downstream genes, heme oxygenase 1 and glutathione peroxidase 4. In mice with asthma, DEX treatment induced the expression of these antioxidant genes and the activation of Nrf2, whereas ML385 (an inhibitor of Nrf2) partially abrogated the antioxidative and therapeutic effects of DEX. To the best of our knowledge, the present study is the first to demonstrate the protective effect of DEX on Th2‑dominant asthma through the activation of the Nrf2 signaling pathway. The results suggested that the antioxidative properties of DEX could be beneficial in clinical application of DEX for the relief of asthmatic symptoms.

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