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題名: New therapeutic strategy of hinokitiol in haemorrhagic shock-induced liver injury
作者: Lu, Wan-Jung;Lin, Kuan-Hung;Tseng, Mei-Fang;Yuan, Kuo-Ching;Huang, Hung-Chang;Sheu, Joen-Rong;Chen, Ray-Jade
貢獻者: 視光學系
關鍵詞: Hemorrhagic shock;hinokitiol;liver;resuscitation;trauma
日期: 2019-03-01
上傳時間: 2025-08-11 14:44:15 (UTC+8)
摘要: Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia-reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone-related compound, exhibits antiplatelet and anti-inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R-induced hepatic injury. Hinokitiol could inhibited NF-κB activation and IL-6 and TNF-α upregulation in liver tissues. Moreover, hinokitiol reduced caspase-3 activation, upregulated Bax and downregulated Bcl-2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)-induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R-induced caspase-3 activation, PPAR cleavage, Bax overexpression and Bcl-2 downregulation. Moreover, hinokitiol attenuated H/R-stimulated NF-κB activation and reduced the levels of IL-6 and TNF-α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF-κB activation.
關聯: Journal of Cellular And Molecular Medicine, 23, 1723-1734. https://doi.org/10.1111/jcmm.14070
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