title: Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Fatih Yaşar
authors.affiliation: Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: Riza
authors.initials: R
authors.lastname: Ozdemir
authors.affiliation: Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: Enver
authors.initials: E
authors.lastname: Ihtiyar
authors.affiliation: Department of Physiology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Erkasap
authors.affiliation: Department of Biochemistry, University of Afyon Kocatepe Medical Faculty, Afyon, Turkey.
authors.forename: Tülay
authors.initials: T
authors.lastname: Köken
authors.affiliation: Department of Histology and Embryology, University of Afyon Kocatepe Medical Faculty, Afyon, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Tosun
authors.affiliation: Department of Biostatistics, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: Setenay
authors.initials: S
authors.lastname: Oner
authors.affiliation: Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Erkasap
keywords: abdominal compartment syndrome; apoptosis; doxycycline; intestinal ischemia-reperfusion injury