Proanthocyanidin Protects Intestine and Remote Organs Against Mesenteric Ischemia/Reperfusion Injury Ali Sizlan Æ Ahmet Guven Æ Bulent Uysal Æ Omer Yanarates Æ Abdulkadir Atim Æ Emin Oztas Æ Ahmet Cosar Æ Ahmet Korkmaz Published online: 29 April 2009 Ó Socie ´te ´ Internationale de Chirurgie 2009 Abstract Background Intestinal ischemia/reperfusion (IR) induces a systemic inflammatory response and releases harmful substances that may affect the function and integrity of distant organs such as lung, liver, and kidney. We con- ducted this study to find out if proanthocyanidins (PA) has protective effects against mesenteric IR injury and mes- enteric IR-induced intestinal and distant organ injury. Materials and methods Thirty-two Sprague-Dawley rats were divided into four groups: control, control ? PA, IR, IR ? PA. The IR and IR ? PA groups were subjected to mesenteric arterial ischemia for 60 min and reperfusion for 6 h. The Control ? PA and IR ? PA groups were administered PA (100 mg/kg/day via oral gavage) for 7 days prior to injury insult. We collected ileal and distant organ tissues, such as pulmonary, hepatic, and kidney specimens to measure tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxi- dase (GPx), and nitrite plus nitrate (NO x ), and we then evaluated histological changes. Results In the IR group, significant increases in MDA and NO x levels and significant increases in SOD and GPx activities of intestine, liver, kidney, and lung were observed. The MDA and NO x levels were significantly lower, as were the SOD and GPx activities in the IR ? PA group than that in the IR group. Although the intestine and distant organs damage scores were significantly higher in the IR group, these injuries were prevented by PA in the IR ? PA group. Conclusions This study demonstrates that PA has a sig- nificant effect in the protection of the intestine and the remote organs against mesenteric IR injury. Introduction Ischemia followed by reperfusion causes characteristic injuries to the intestine, such as necrotizing enterocolitis, midgut volvulus, incarcerated hernia, cardiopulmonary bypass, multiple traumas, shock, and sepsis [1, 2]. More- over, intestinal ischemia/reperfusion (IR) injury may develop as a consequence of mesenteric ischemia caused by any one of a number of factors, including enhanced endogenous vasocontractile substances [3] or such drugs as sumatriptan [4]. Despite decades of research in this area, IR injury remains a clinically challenging problem [1, 5]. Ischemia/reperfusion injury of the intestine is complex and multifactorial pathophysiological process that involves the actions of reactive oxygen species (ROS), reactive nitrogen species (RNS), inflammatory cytokines, nitric oxide (NO), and polymorphonuclear lymphocytes (PMNL). Reperfusion of the intestine causes the activation and adhesion of PMNL, with the release of proinflammatory substances and the formation of free radicals [6–8]. Moreover, the NO produced by inducible nitric oxide synthases (iNOS) is converted to a peroxynitrite (ONOO) A. Sizlan Á O. Yanarates Á A. Atim Á A. Cosar Department of Anesthesiology and Reanimation, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey A. Guven (&) Department of Pediatric Surgery, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey e-mail: drahmetguven@yahoo.com B. Uysal Á A. Korkmaz Department of Physiology, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey E. Oztas Department of Medical Histology and Embryology, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey 123 World J Surg (2009) 33:1384–1391 DOI 10.1007/s00268-009-0011-9