Attenuation of renal ischemia-reperfusion injury by FR167653 in dogs.
BACKGROUND
Inflammatory cytokines are known to contribute to ischemia-reperfusion injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin-1beta and tumor necrosis factor-alpha, on ischemia-reperfusion injury of the kidney in dogs.


METHODS
The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n = 10) and an FR group (n = 8) were evaluated for tissue blood flow; resistive index, pulsatility index, arterial oxygen pressure, serum creatinine, blood urea nitrogen, aspartate transaminase, and alanine transaminase levels; interleukin-1beta messenger RNA expression in the peripheral blood; apoptotic index; and histopathology.


RESULTS
The FR group showed lower creatinine, serum urea nitrogen, aspartate transaminase, and alanine transaminase levels (P <.038 each) and lower interleukin-1beta mRNA expression and apoptotic index (P <.041 each) than did the control group. Arterial oxygen pressure during the 120 minutes after reperfusion in the FR group decreased but recovered quickly (P =.024). Renal tissue damage in the FR group was less than that in the control group (P =.036).


CONCLUSIONS
FR ameliorates ischemia-reperfusion injury of the kidney potentially by reduced production of inflammatory cytokines that may contribute to damage to the ischemic kidney and the distant organs.
Kitada
Hidehisa
H
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sugitani
Atsushi
A
Yamamoto
Hirofumi
H
Otomo
Naoki
N
Okabe
Yasuhiro
Y
Inoue
Shigetaka
S
Nishiyama
Ken-ichi
K
Morisaki
Takashi
T
Tanaka
Masao
M
D000818:Animals; D017209:Apoptosis; D004285:Dogs; D005260:Female; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha