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Objective: To investigate the effects and mechanisms of zingerone on LPS-induced acute lung injury (ALI) in vivo. Methods:The mice were divided into control group, zingerone group, LPS group, and LPS + zingerone group. Each group was injected intraperitoneally with zingeroneor saline. The mice were injected with LPS after zingerone treatment for 2h and then were sacrificed 4h later. We collected the lung tissue and blood of the mice and determined lung injury by HE staining. Tunnel staining was performed for cell apoptosis. The concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by ELISA assay. And the protein levels of nuclear factor (erythroid-derived2)-like 2 protein (Nrf2) and heme oxygenase-1 (HO-1) were measured by immuno-blot method. And the above-mentioned experiments were repeated by using Nrf2 knockout mice. Results: Compared with those in control group, the lung injury of mice in LPS group aggravated and cell apoptosis rate was increased significantly. Compared with LPS group, the injury was alleviated and apoptosis rate was decreased markedly. Meanwhile, the concentrations of inflammatory cytokines, including IL-6, TNF-α, IL-1β and MDA, were up-regulated notably compared with the control group, the concentration of SOD was decreased; the concentrations of IL-6, TNF-α, IL-1β and MDA in LPS + zingerone group were decreased while SOD was increased compared with LPS group. In addition, LPS inhibited the expressions of Nrf2 and HO-1, zingerone up-regulated the protein levels of Nrf2 and HO-1. After knockdown of Nrf2 gene, the effects of zingerone on lung injury, inflammation and oxidative stress in the mouse model of LPS-induced acute lung injury were weakened. Conclusion: Zingerone alleviates lung injury in mice by inhibiting inflammation and oxidative stress through activating Nrf2 pathway.
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<p><b>OBJECTIVE</b>To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes.</p><p><b>METHODS</b>Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis.</p><p><b>RESULTS</b>Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V.</p><p><b>CONCLUSION</b>Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.</p>