New therapeutic strategy of hinokitiol in haemorrhagic shock‐induced liver injury

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.