Prostaglandins, Leukotrienesand Essential FattyAcids (1996) 55(6), 379-383 © PearsonProfessionalLtd 1996 The effects of indomethacin, NDGA, allopurinol and superoxide d,smutase on prostaglandin E2 and leukotriene C4 levels after mesenteric ischemia. reperfusion injury M. Sare, ~ S. Bozkurt, 2 E. Onuk, 2 M. Oguz, 2 M. Gurel, 1 S. Ercan 3 l ln6nO University, Faculty of Medicine, Department of General Surgery, Malatya, Turkey 2Gazi University, Faculty of Medicine, Department of General Surgery, Ankara, Turkey SGazi University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey Summary In this study, the changes of arachidonic acid metabolites after an ischemia-reperfusion (I/R) period are investigated. The cyclooxygenase and lipoxygenase metabolites were found to be significantly increased after a 45 min period of ischemia followed by 5 min of reperfusion. Prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-Iike activities did not change in the ischemic period, but they both increased after reperfusion. A cyclooxygenase inhibitor indomethacin and lipoxygenase inhibitor nordehydroguaretic acid (NDGA) decreased PGEg- and LTC4-1ike activities, respectively, while allopurinol and superoxide dismutase (SOD) decreased both activities. According to our results, it can be assumed that free oxygen radicals are responsible for the elevation of PGE2- and LTC4-1ike activites and both of these arachidonic acid metabolites and free oxygen radicals are the main necrotizing agents in ischemia-reperfusion induced damage. INTRODUCTION The significance of rnesenteric artery occlusion is a well-known phenomenon and the physiologic changes occurring after embolectomy have been a subject for many studies. Tissue changes and formation of thrombo- sis are the most frequently encountered incidents occur- ring after an ischemia-reperfusion (I/R) period. In recent years, oxygen-derived free radicals (ODFR) were blamed for the tissue damage following an I/R period. 1,2 The inhibition of enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase leads to tissue destruction. The mechanism of reperfusion injury has been studied in the feline intestine and the role of 02- has been confirmed. Thus, SOD protects against the increased capillary permeability and the mucosal lesions Received 14 September 1995 Accepted 5 February 1996 Correspondence to: Dr Mustafa Sare, P.K. 18 Karakas PTT M0d, Malatya, Turkey, Tel. 90-422-3224939; Fax. 09-422-3230445. imposed by 3 h of ischemia. Pretreatment of the animals with allopurinol, to inhibit xanthine oxidase, also affords protection.3-~ I/R causes increased malondialdehyde con- tent and increased myeloperoxidase and phospholipase Az (PLA2) activity in the mucosa. PLA 2 is involved in the generation of a variety of bioactive and potentially toxic lipid metabolites, such as arachidonic acid metabolites, lysophospholipids, and platelet-activating factor (PAF)Y Oxidants have been reported to activate the enzyme PLA2, which results in the production of a number of proinflammatory agents including leukotriene B4 (LTB4) and PAF. There have been several in vivo studies demon- strating that LTB4 and PAF may play an important role in mediating the granulocyte accumulation elicited by reperfusion.9 LTB 4 production in intestine has been signi- ficantly increased following I/R. 1°,11 From LTA4, an epoxide hydrolyase generates LTB4, and a glutatahione-S-trans- ferase adds glutathione to form LTC4? 2 A wide variety of cells, organelles and enzymes may be involved in the free radical formation activated by ischemia and reperfusion; 379