Pharmacological Research 48 (2003) 397–403 The effects of caffeic acid phenethyl ester on tissue damage in lung after hindlimb ischemia-reperfusion Mukadder Çalikoglu a,∗ , Lulufer Tamer b , Nehir Sucu c , Banu Coskun d , Bahadir Ercan e , Ali Gul f , Ilker Calikoglu g , Arzu Kanik h a Department of Chest Disease, Mersin University School of Medicine, Mersin, Turkey b Department of Biochemistry, Mersin University School of Medicine, Mersin, Turkey c Department of Cardiovascular Surgery, Mersin University School of Medicine, Mersin, Turkey d Department of Histology, Mersin University School of Medicine, Mersin, Turkey e Department of Biochemistry, Mersin University School of Medicine, Mersin, Turkey f Department of Cardiovascular Surgery, Mersin University School of Medicine, Mersin, Turkey g Clinic of Biochemistry, Silifke Government State Hospital, Mersin, Turkey h Department of Biostatistic, Mersin University School of Medicine, Mersin, Turkey Accepted 16 April 2003 Abstract Aim: The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) on the lungs as a remote organ after performing hindlimb ischemia-reperfusion (I/R) and by assessing biochemical and histopathological analysis. Methods: The animals were divided into three groups: control, I/R, and I/R with CAPE. I/R period for 8 h was performed on the right hindlimb of all the anesthesied rats in I/R and CAPE with I/R group. In the CAPE with I/R group, the animals received CAPE 10 M by intraperitoneal injection 1 h before the reperfusion. The animals in the control and I/R groups received a similar volume of saline solution by means of intraperitoneal injection. At the end of the reperfusion period, a midsternotomy was performed. Blood, bronchoalveolar lavage (BAL) and lung tissue were obtained, and were used for biochemical and histopathological examination. Results: The tissue and serum malondyaldehyde levels were significantly lower in the control (P = 0.0001 and 0.001, respectively) and in the CAPE with I/R groups (P = 0.0001 and 0.003, respectively) compared to the I/R group. Tissue Na + -K + ATPase activity in the CAPE with I/R group was significantly higher than in the I/R group (P = 0.0001). Reduced activity was found in the I/R group compared to the control group (P = 0.0001). Myeloperoxidase activity (P = 0.001) and protein concentration (P = 0.034) in BAL were significantly reduced in CAPE-treated animals when compared with the I/R group. A decreased activity and protein concentration were found in the control group compared to the I/R group (P = 0.0001 and 0.024, respectively). The lungs of the I/R group displayed intense peribronchial and perivascular leukocytic infiltration in histopathological examination compared to the CAPE with I/R group (P< 0.05). Conclusion: CAPE seems to be effective in protecting remote organ injury caused by increased oxidative stress and neutrophil accumu- lation that results from an I/R injury. © 2003 Elsevier Ltd. All rights reserved. Keywords: Caffeic acid phenethyl ester; Ischemia-reperfusion; Lung 1. Introduction An ischemia-reperfusion (I/R) injury is a complex phe- nomenon seen often in surgical practice. Typically, it is associated with both local injury and induction of systemic inflammatory response [1]. This injury is not only limited to ∗ Corresponding author. Tel.: +90-324-337-43-00; fax: +90-324-337-43-05. E-mail address: mcalikoglu@hotmail.com (M. Çalikoglu). organs directly affected by I/R but also found in distant or- gans [2]. It is well-recognized that an I/R injury is character- ized by an increase in reactive oxygen species (ROS) [2–4]. ROS stimulate the release and the formation of various in- flammatory mediators with powerful chemotactic potential. These mediators lead to leukocyte activation and endothe- lial adhesion molecule expression and vascular endothelial damage in remote organs [4]. At the same time, ROS are capable of reacting with proteins, nucleic acids, and lipids leading to lipid peroxidation of biological membranes. 1043-6618/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S1043-6618(03)00156-7