Effects of Doxycycline on Renal Ischemia Reperfusion Injury Induced by Abdominal Compartment Syndrome Enver _ Ihtiyar, M.D.,* ,1 N. Fatih Yas xar, M.D.,* Nilu¨ fer Erkasap, M.D.,† Tu¨ lay Ko¨ken, M.D.,‡ Murat Tosun, M.D.,§ Setenay O ¨ ner, M.D.,jj and Serdar Erkasap* *Department of General Surgery; †Department of Physiology; jj Department of Biostatistics, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey; ‡Department of Biochemistry; and §Department of Histology, Embryology, University of Afyon Kocatepe Medical Faculty, Afyon, Turkey Submitted for publication March 18, 2009 Background. The aim of this study was to determine the effects of doxycycline on renal ischemia reperfu- sion (I/R) injury in a rat model of abdominal compart- ment syndrome (ACS). Materials and Methods. Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no ma- nipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respec- tively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and simi- larly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1b, IL-6, TNF-a, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immuno- histochemically. Results. Creatinine, MDA, IL-1b, and IL-6 levels were significantly higher in group 3, 1h after the reper- fusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1hour after decompression. However, there remained no difference between groups at 24h, except IL-1b, which was decreased to even lower values. TNF-a and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expres- sion of bcl-2 was significantly less in the groups in which doxycycline was administered. Conclusion. Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2. Ó 2011 Elsevier Inc. All rights reserved. Key Words: abdominal compartment syndrome; renal ischemia-reperfusion injury; doxycycline; apoptosis. INTRODUCTION The pressure within the abdominal cavity is normally atmospheric or subatmospheric and intra-abdominal hypertension (IAH) affects each organ system sepa- rately at different levels of pressure [1]. Abdominal compartment syndrome (ACS) refers to organ dysfunc- tion and ischemia resulting from IAH. However, increased intra-abdominal pressure reduces blood flow to intra-abdominal organs, and decompression may cause another serious problem, ischemia/reperfu- sion (I/R) injury [2–4]. It is well-known that reperfusion of ischemic tissue may promote the generation of various reactive oxygen metabolites, which have deleterious effects on cell membranes by mediating lipid peroxidation. MDA, which arises from the breakdown of lipid peroxyl radicals, is one of the indicators of oxidative stress. MDA is also important, in which it can cause further oxidative injury by oxidizing protein molecules [5]. Oxidants released during the reperfusion of ischemic tissue stimulate transcription factors involved in the expression of tumor necrosis factor-alpha (TNF-a). 1 To whom correspondence and reprint requests should be addressed at General Surgery Department, Eskisehir Osmangazi University, Eskisehir, Turkey 26480. E-mail: eihtiyar@ogu.edu.tr. 0022-4804/$36.00 Ó 2011 Elsevier Inc. All rights reserved. 113 Journal of Surgical Research 167, 113–120 (2011) doi:10.1016/j.jss.2009.09.048