title: Attenuation of renal ischemia-reperfusion injury by FR167653 in dogs.
abstract: 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.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Kitada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugitani
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Otomo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okabe
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Inoue
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: 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
chemical_list: C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha