dehydroxymethylepoxyquinomicin and Reperfusion-Injury

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.

Topics: Animals; Apoptosis; Benzamides; Cyclohexanones; Glycyrrhizic Acid; Heart Transplantation; HMGB1 Protein; Male; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Neutrophil Infiltration; NF-kappa B; Peroxidase; Reperfusion Injury; Troponin T

Nuclear factor-kappaB regulates the expression of several genes involved in inflammation, the immune response, apoptosis, cell survival, and proliferation. Many of these same genes are activated during ischemia/reperfusion (I/R) injury. Here, we examined the anti-inflammatory efficacy of a newly developed nuclear factor-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in the intestinal I/R injury model of rats.. Intestinal ischemia was induced by occluding the superior mesenteric artery for 60 min. The experimental animals were divided into two groups: untreated group, control; treated group, DHMEQ-treated (20 mg/kg). DHMEQ were administered intraperitoneally at 60 min prior to clamping and 5 min prior to reperfusion. Animal survival rates, intestinal tissue blood flow, serum levels of tumor necrosis factor-alpha, and interleukin-6, and the histopathology of both the intestine and the lung were analyzed.. The DHMEQ-treated animals exhibited higher values of intestinal tissue blood flow and suppression of tumor necrosis factor-alpha and interleukin-6 production, resulting in marked prolongation of their survival times. Histopathological findings obtained by examining tissues from control animals revealed severe intestinal mucosal damage and disruption of the lung alveolar architecture accompanied by hemorrhage and marked neutrophilic infiltration. These findings were significantly ameliorated in DHMEQ-treated animals.. DHMEQ effectively prevented both intestine and lung injuries in rat intestinal I/R models. This agent may possess a good potency for clinical application in various pathological settings including intestinal I/R and/or inflammatory acute lung injury.

Topics: Animals; Anti-Inflammatory Agents; Benzamides; Cyclohexanones; Disease Models, Animal; Intestinal Diseases; Lung Diseases; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Reperfusion Injury