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

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 proinflammatory 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)