Dexmedetomidine Attenuates Oxidative Stress Induced Lung Alveolar Epithelial Cell ApoptosisIn Vitro

Abstract

Background. Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α 2 adrenoceptor agonist dexmedetomidine (Dex) from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2) and the underlying mechanisms. Methods. The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 μM H2O2 with or without Dex (1 nM) or Dex in combination with atipamezole (10 nM), an antagonist of α 2 receptors. Their effect on mitochondrial membrane potential (Δψ m), reactive oxygen species (ROS), and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR), ERK1/2, and E-cadherin expression were also determined with immunocytochemistry. Results. Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole. Conclusion. Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.

Decreased expression of E‐cadherin by Porphyromonas gingivalis‐lipopolysaccharide attenuates epithelial barrier function

“…Previous studies showed that inflammatory mediators reduced E‐cad expression in the epithelium . Fujita et al .…”

“…Recent studies have demonstrated a decrease in E‐cad expression in the gingival epithelium of gingivitis and periodontitis . In addition, it has been reported that some inflammatory mediators such as tumor necrosis factor‐α (TNF‐α) and ROS decrease E‐cad expression in human epithelial cells . However, whether there is a relationship between E‐cad expression and barrier function in human gingival epithelial cells stimulated with microbial toxic products has not been fully clarified yet.…”

“…Furthermore, to clarify the mechanism of the E‐cad decrease induced by P. gingivalis ‐LPS, we focused on ROS that was reported to induce a decrease in E‐cad expression in lung epithelial cells and pancreatic epithelial cells . Then, we analyzed ROS involvement in the process of E‐cad reduction by the addition of the antioxidants vitamin C (VC), vitamin E (VE) and l ‐ascorbic acid 2‐phosphate magnesium salt (APM) to human gingival epithelial cells.…”

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

“…Therein, activated Bax can permeabilize the mitochondrial membrane, leading to the release of cytochrome c and subsequent cascade activations of caspases‐9, ‐3, and ‐6 [Ow et al, ]. In lung alveolar epithelial cells, Cui et al [] showed that dexmedetomidine could downregulate the Bax‐mediated signals and then attenuate hydrogen peroxide‐induced programmed cell death. In rats with intracerebral hemorrhage, dexmedetomidine was shown to alleviate impairment of short‐term and spatial learning memory by enhancing brain‐derived neurotrophic factor expression and suppressing apoptosis [Hwang et al, ].…”

Potential protective effect of arginine against 4-nitrophenol-induced ovarian damage in rats

“…Oxidative stress is frequently cited to explain cell damage in various diseases. Cells have evolved an array of antioxidant defense systems to protect against the harmful effect of exogenous matters (Cui et al, 2015). Under oxidative condition, some antioxidants are tremendously synthesised to inhibit oxidation or reactions promoted by oxygen, peroxides, or free radicals or their actions.…”