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).


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, 1 cc 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, 1 hour 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.


CONCLUSIONS
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.
Ihtiyar
Enver
E
Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey. eihtiyar@ogu.edu.tr
Yaşar
N Fatih
NF
Erkasap
Nilüfer
N
Köken
Tülay
T
Tosun
Murat
M
Oner
Setenay
S
Erkasap
Serdar
S
D000005:Abdomen / Q000098:blood supply*; D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D003161:Compartment Syndromes / Q000150:complications*; D016207:Cytokines / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D023421:Models, Animal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D004318:Doxycycline