Nephrol Dial Transplant (2002) 17: 399-407
© 2002 European Renal Association-European Dialysis and Transplant Association
Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice
Department of Gastroenterology and Nephrology, and Division of Blood Purification, 1 Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, and 2 Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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-1ß, tumour necrosis factor-
, 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.
Conclusion. 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.
Keywords: FR167653; kidney; monocyte chemoattractant protein-1; p38 mitogen-activated protein kinase; reperfusion
Correspondence and offprint requests to: Dr Kengo Furuichi, Department of Gastroenterology and Nephrology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan. Email: kfuruichi{at}medf.m.kanazawa\|[hyphen]\|u.ac.jp
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