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.

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.

• Authors: Kengo Furuichi, Takashi Wada, Yasunori Iwata, Norihiko Sakai, Keiichi Yoshimoto, Ken-ichi Kobayashi Ki, Naofumi Mukaida, Kouji Matsushima, Hitoshi Yokoyama
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 17 Issue 3 Pg. 399-407 (Mar 2002) ISSN: 0931-0509 [Print] England
• PMID: 11865084 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Chemokine CCL2
• Chemokine CCL5
• Enzyme Inhibitors
• FR 167653
• Interleukin-1
• Pyrazoles
• Pyridines
• Tumor Necrosis Factor-alpha
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
• Cells, Cultured
• Chemokine CCL2 (genetics)
• Chemokine CCL5 (genetics)
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Humans
• Interleukin-1 (genetics)
• Kidney (drug effects, injuries, metabolism, pathology)
• Kidney Tubular Necrosis, Acute (pathology, prevention & control)
• Male
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Pyrazoles (pharmacology)
• Pyridines (pharmacology)
• Reperfusion Injury (genetics, metabolism, pathology, prevention & control)
• Transcription, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (genetics)
• p38 Mitogen-Activated Protein Kinases