Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and β-cell lymphoma 2 (βcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1β, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of βcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.