Effects of Doxycycline on Renal Ischemia Reperfusion Injury Induced by Abdominal Compartment Syndrome

Background. The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment 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 manipulation; 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, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1 beta, IL-6, TNF-alpha, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. Results. Creatinine, MDA, IL-1 beta, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion 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-1 beta, which was decreased to even lower values. TNF-alpha 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 expression 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-inflammatorycytokines, increasingthelevel of TIMP-1, and inhibiting the activity of MMP-2. (C) 2011 Elsevier Inc. All rights reserved.