title: Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice.
abstract: BACKGROUND
  Various types of chemokines/cytokines play important roles in ischaemia/reperfusion injury in kidneys. However, the roles of p38 mitogen-activated protein kinase (MAPK) in the inflammatory processes of renal ischaemia/reperfusion injury remain to be investigated. We explored the effect of FR167653, a specific inhibitor of p38 MAPK, on renal ischaemia/reperfusion injury in mice.
  
  
  METHODS
  The renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. FR167653 was injected 2 h before or 24 h after renal vessel clamp. Renal tissues were removed for pathological examination 4, 24 or 48 h after reperfusion.
  
  
  RESULTS
  We observed a large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischaemia/reperfusion injury in mice. FR167653 significantly decreased cell infiltration into outer medulla, and the extent of acute tubular necrosis 24 and 48 h after reperfusion. FR167653 markedly decreased the transcription of interleukin-1beta, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and regulated upon activation, normal T cell expression and secreted in diseased kidneys. Moreover, FR167653 decreased the number of phosphorylated p38 MAPK-positive cells 4 h after reperfusion.
  
  
  CONCLUSIONS
  These results suggest that FR167653 markedly ameliorated renal ischaemia/reperfusion injury, possibly by inhibiting cytokine/chemokine expression and consequent phosphorylation of p38 MAPK in renal tissue.
authors.affiliation: Department of Gastroenterology and Nephrology, and Division of Blood Purification, Cancer Research Institute, Kanazawa University, Tokyo, Japan. kfuruichi@medf.m.kanazawa-u.ac.jp
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.forename: Norihiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kobayashi Ki
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D004791:Enzyme Inhibitors; C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases