Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine protects gastric mucosal epithelial cells against ischemia/reperfusion-induced apoptosis by inhibiting HMGB1-mediated inflammation and oxidative stress

Tianpin Liu^1,2, Bing Wang³, Qiong Han³, Wansheng Gong³, Juan Ye⁴

¹Department of Anesthesiology, The First College of Clinical Medical Science, China Three Gorges University, China; ²Department of Anesthesiology, Yichang Central People’s Hospital, Yichang, Hubei Province 443003, China; ³Department of Anesthesiology, Yichang Zigui County People’s Hospital, Yichang, Hubei Province 443600, China; ⁴Department of Anesthesiology, Banan Hospital of Chongqing Medical University, Chongqing 401320, China.

For correspondence:- Juan Ye Email: juan_ye81@163.com Tel:+862366293462

Accepted: 12 June 2022 Published: 31 July 2022

Citation: Liu T, Wang B, Han Q, Gong W, Ye J. Dexmedetomidine protects gastric mucosal epithelial cells against ischemia/reperfusion-induced apoptosis by inhibiting HMGB1-mediated inflammation and oxidative stress. Trop J Pharm Res 2022; 21(7):1411-1417 doi: 10.4314/tjpr.v21i7.8

© 2022 The authors.
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Abstract

Purpose: To investigate the role of dexmedetomidine in gastric ischemia/reperfusion injury using gastric mucosal epithelial cell (GES-1) model.

Methods: GES-1 were subjected to oxygen-glucose deprivation conditions, followed by increasing dexmedetomidine concentrations (0.5, 1.0, or 1.5 μM) for 4 h of reoxygenation. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry, respectively. Oxidative stress and inflammation were analyzed by enzyme-linked immunosorbent assay (ELISA).

Results: Oxygen-glucose deprivation conditions induced cytotoxicity in GES-1 by decreasing cell viability and increasing apoptosis. Dexmedetomidine treatment significantly increased the cell viability of hypoxia/reoxygenation-induced GES-1 (p < 0.01) but reduced apoptosis. Dexmedetomidine also attenuated the hypoxia/reoxygenation-induced increase in malondialdehyde and myeloperoxidase, but the decrease in superoxide dismutase and glutathione in GES-1. Moreover, upregulated tumor necrosis factor-α, interleukin (IL)-1β, and IL-18 in hypoxia/reoxygenation-induced GES-1 was downregulated by dexmedetomidine treatment. Dexmedetomidine also enhanced IL-10 levels and inhibited pro-inflammatory factor production (p < 0.01). High-mobility group box 1 (HMGB1) protein in GES-1 was upregulated by hypoxia/reoxygenation but decreased by dexmedetomidine. HMGB1 over-expression attenuated the dexmedetomidine-induced increase in cell viability and the decrease in apoptosis, oxidative stress, and inflammation in hypoxia/reoxygenation-induced GES-1 (p < 0.01).

Conclusion: Dexmedetomidine protects GES-1 against ischemia/reperfusion-induced apoptosis, inflammation, and oxidative stress by inhibiting HMGB1, thus providing a potential strategy for treating gastric ischemia/reperfusion injury.

Keywords: Dexmedetomidine, gastric mucosal epithelial cells, Ischemia/reperfusion, Apoptosis, Inflammation, Oxidative stress, High-mobility group box 1 (HMGB1)