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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The antiinflammatory agent SC-41930 inhibits granulocyte infiltration of the rodent dermis induced by 6-trans-leukotriene B4.

Granulocyte diapedesis in response to the generation of defined chemotaxins such as leukotriene B4 (LTB4), 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE], C5a, platelet activating factor and others is a hallmark of the inflammatory process that is thought to contribute to the tissue pathology seen in a number of diseases. 6-trans-LTB4 arises through the myeloperoxidase (MPO)-dependent metabolism of sulfidopeptide leukotrienes and through the action of 5-lipoxygenase on 12(R)-HETE. The intradermal (i.d.) injection of 6-trans-LTB4 induces a dose and time dependent influx of granulocytes into the guinea-pig (Hartley) dermis. When various doses of the LTB4 receptor antagonist and antiinflammatory agent, SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro- 8-propyl-2H-1-benzopyran-2-carboxylic acid) given 30 min ahead of i.d. injection of 6-trans-LTB4 (10 micrograms/i.d. site), granulocyte infiltration, as assessed by dermal levels of the neutrophil marker enzyme MPO was inhibited with an ED50 value of 9.8 mg/kg in the guinea-pig. When various doses (10-25 micrograms) 6-trans-LTB4 were injected in the mouse (CD-1) dermis, there was a dose-related increase in granulocyte accumulation at 4 h. Furthermore when mice were pretreated (-30 min) with SC-41930 (1 mg/kg) orally, the trafficking of granulocytes was inhibited (p less than .01) as assessed by dermal MPO levels. SC-41930 orally inhibits 6-trans-LTB4-induced granulocyte accumulation in the guinea-pig more potently than against the response to 12(R)-HETE(ED50:13.4 mg/kg) but less potently than against LTB4 (ED50:0.6 mg/kg). These multiple activities may contribute to this compound's potential as an inflammatory agent.[1]

References

  1. The antiinflammatory agent SC-41930 inhibits granulocyte infiltration of the rodent dermis induced by 6-trans-leukotriene B4. Fretland, D.J., Widomski, D.L., Anglin, C.P., Gaginella, T.S. Prostaglandins Leukot. Essent. Fatty Acids (1991) [Pubmed]
 
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