The Novel NF-κB Inhibitor, Dehydroxymethylepoxyquinomicin, Prevents Local and Remote Organ Injury Following Intestinal Ischemia/Reperfusion in Rats

• Published in: The Journal of surgical research Vol. 149; no. 1; pp. 69 - 75
• Main Authors: Suzuki, Tomomi, M.D, Yamashita, Kenichiro, M.D, Jomen, Wataru, M.D, Ueki, Shinya, M.D, Aoyagi, Takeshi, M.D, Fukai, Moto, M.D, Furukawa, Hiroyuki, M.D, Umezawa, Kazuo, Ph.D, Ozaki, Michitaka, M.D., Ph.D, Todo, Satoru, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2008; Elsevier
• Subjects: ARDS; Biological and medical sciences; DHMEQ; General aspects; ischemia-reperfusion; Medical sciences; NF-kB inhibitor; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; small bowel transplantation; Surgery; small bowel transplantation; ischemia-reperfusion; NF-kB inhibitor; DHMEQ; ARDS; Rat; Transplantation; Small intestine; Prevention; Signal transduction; Surgery; Intestinal ischemia; Graft; Intestinal disease; Transcription factor NFκB; Lung disease; Respiratory disease; Ischemia reperfusion; Severe acute respiratory syndrome; Rodentia; Trauma; Infection; Medicine; Vertebrata; Mammalia; Treatment; Adult respiratory distress syndrome; Viral disease; Animal; Digestive diseases; Inhibitor; Lesion; ischemia- reperfusion; Organ
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.01.020

Background Nuclear factor-κB 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-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in the intestinal I/R injury model of rats. Materials and methods 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. Results 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. Conclusion 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.