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

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.

Echinochrome exhibits anti-asthmatic activity through the suppression of airway inflammation, oxidative stress, and histopathological alterations in ovalbumin-induced asthma in BALB/c mice

“…At the same time, a significant rise was shown in the Ech treatment groups. Previous research indicated that OVA administration decreased GSH levels, which were then correlated to their deletion as a result of lipid peroxidation and ROS generation (Xiao et al 2023 ). CAT can alleviate cell damage by converting H 2 O 2 into water and oxygen (Sahiner et al 2018 ).…”

Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells

“…Activation of Nrf2 limits allergen-induced asthma ( 26 ), whereas DMF promotes the expression of Nrf2 to modulate inflammation ( 27 ). Following this, we hypothesized that the DMF-induced increased Tregs population depends on Nrf2 signaling.…”

Ferroptosis triggers airway inflammation in asthma

“…122 Nrf2 increases the antioxidant genes, including HO-1, GPX4, which serves an important role in maintaining redox balance in asthma. 103 It is reported that Nrf2-Keap1 signaling pathway promotes the activation of system Xc-, the expression of GPX4, and regulates the activity of SLC7A11, 123,124 to reduce the production of ROS, which ultimately inhibits ferroptosis. 125 It is suggested that Nrf2 activator ameliorates airway inflammation and oxidative stress in asthmatic mice.…”

“…Glutathione (GSH) is the most abundant antioxidant in the airway epithelial lining fluid and is involved in various important functions relevant to asthma. 103 It is suggested that the airway GSH/ glutathione oxidized (GSSG) redox balance is unbalanced in asthma. 104 Ferroptosis caused by abnormal metabolism of amino acids is mainly related to abnormal metabolism of GSH.…”