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 sam...

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Published in:The Journal of surgical research 2011-05, Vol.167 (1), p.113-120
Main Authors: İhtiyar, Enver, M.D, Yaşar, N. Fatih, M.D, Erkasap, Nilüfer, M.D, Köken, Tülay, M.D, Tosun, Murat, M.D, Öner, Setenay, M.D, Erkasap, Serdar
Format: Article
Language:English
Subjects:
Abdomen
Abdomen - blood supply
abdominal compartment syndrome
Acute Kidney Injury - etiology
Acute Kidney Injury - metabolism
Acute Kidney Injury - prevention & control
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
apoptosis
Apoptosis - drug effects
Biological and medical sciences
Compartment Syndromes - complications
Cytokines - metabolism
doxycycline
Doxycycline - pharmacology
Doxycycline - therapeutic use
Female
Gastroenterology. Liver. Pancreas. Abdomen
General aspects
Kidney - drug effects
Kidney - metabolism
Kidney - pathology
Male
Matrix Metalloproteinase 2 - metabolism
Medical sciences
Models, Animal
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Other diseases. Semiology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Rats, Sprague-Dawley
Regional Blood Flow - physiology
renal ischemia-reperfusion injury
Renovascular diseases
Reperfusion Injury - etiology
Reperfusion Injury - metabolism
Reperfusion Injury - prevention & control
Surgery
Tissue Inhibitor of Metalloproteinase-1 - metabolism
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Summary: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-1β, IL-6, TNF-α, 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-1β, 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-1β, which was decreased to even lower values. TNF-α 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-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2009.09.048