%0 Journal Article
%T Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation
%A Fadhil G. Al-Amran
%A Najah R. Hadi
%A Haider S. H. Al-Qassam
%J ISRN Pharmacology
%D 2013
%R 10.1155/2013/303717
%X Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30£¿min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-¦Á, IL-1¦Â, and ICAM-1 and plasma level of cTnI ( ). Morphologic analysis showed that both MK-886 and DITPA markedly improved ( ) the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway. 1. Introduction Organ transplantation is a unique situation where grafts are successively subjected to global cold ischemia, warm ischemia, and blood reperfusion. These events are believed to impair graft function and aggravate both acute and chronic rejection episodes [1, 2]. The pathophysiology of ischemia/reperfusion (I/R) injury shows several characteristics of inflammatory responses including activation of complement, platelets, and endothelial cells, infiltration of monocytes and neutrophils, and the release of oxygen-derived-free radicals, chemokines, and cytokines [3]. MK-886 is a highly potent inhibitor of leukotriene formation in vivo and in vitro [4]. This compound inhibits leukotriene biosynthesis indirectly by a mechanism through the binding of a membrane-bound 5-lipoxygenase-activating protein (FLAP), thereby inhibiting the translocation and activation of 5-lipoxygenase [5, 6]. MK-886 was found to prevent both post ischemic leukotriene accumulation and the microcirculatory changes after ischemia-reperfusion [7]. MK-886 was also found to be effective in prevention of liver and intestine injury by reducing apoptosis and oxidative stress in a hepatic I/R model. Anti-inflammatory properties and inhibition of lipid peroxidation by MK-886 could be
%U http://www.hindawi.com/journals/isrn.pharmacology/2013/303717/