N Fatih Yaşar1, Riza Ozdemir1, Enver Ihtiyar1, Nilüfer Erkasap2, Tülay Köken3, Murat Tosun4, Setenay Oner5, Serdar Erkasap1. 1. Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey. 2. Department of Physiology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey. 3. Department of Biochemistry, University of Afyon Kocatepe Medical Faculty, Afyon, Turkey. 4. Department of Histology and Embryology, University of Afyon Kocatepe Medical Faculty, Afyon, Turkey. 5. Department of Biostatistics, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
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). 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.
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.
Authors: Emily K Robinson; Daniel P Kelly; David W Mercer; Rosemary A Kozar Journal: JPEN J Parenter Enteral Nutr Date: 2008 Jul-Aug Impact factor: 4.016
Authors: Abdulrahman Al Asmari; Saud Al Omani; Malfi Al Otaibi; Abdul-Aziz Al Abdulaaly; Ibrahim Elfaki; Khalid Al Yahya; Mohammed Arshaduddin Journal: Int J Clin Exp Med Date: 2014-03-15