Nuclear factor-κB activation inhibitor attenuates ischemia reperfusion injury and inhibits Hmgb1 expression

To investigate the effects of nuclear factor-κB activation inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on cardiac ischemia reperfusion injury in a transplantation model.

Hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. Some mice were administrated intraperitoneally with DHMEQ (8 mg/kg) 1 h before reperfusion. For inhibition of Hmgb1, mice were treated with glycyrrhizin at 250 mg/kg prior to reperfusion.

DHMEQ decreased cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by DHMEQ treatment. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with DHMEQ treatment (IR+DHMEQ: 58.6 ± 5.75 ml/min; IR: 25.9 ± 4.1 ml/min; P < 0.05). Furthermore, DHMEQ suppressed high mobility group protein (Hmgb1) expression. And the Caspase 3 activity, the number of TUNEL-positive cardiomyocytes and infiltrated neutrophil in cardiac allograft were markedly decreased with Hmgb1 inhibitor treatment.

Nuclear factor-κB activation inhibitor DHMEQ attenuates ischemia reperfusion injury in a cardiac transplantation model and it may be a suitable agent for the protection of the cardiac against ischemia reperfusion injury.