fr-167653 and Kidney-Tubular-Necrosis--Acute

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.. 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.. 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.. 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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Enzyme Inhibitors; Humans; Interleukin-1; Kidney; Kidney Tubular Necrosis, Acute; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Pyrazoles; Pyridines; Reperfusion Injury; Transcription, Genetic; Tumor Necrosis Factor-alpha