Ebselen reduces the formation of LTB4 in human and porcine leukocytes by isomerisation to its 5S, 12R-6-trans-isomer |
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Authors: | Peter Kuhl Harald O Borbe Hartmut Fischer Axel Rmer Hasan Safayhi |
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Institution: | Peter Kuhl, Harald O. Borbe, Hartmut Fischer, Axel Römer,Hasan Safayhi |
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Abstract: | Ebselen, a new organoselenium compound with pronounced anti-inflammatory properties, selectively inhibits the formation of leukotriene B4 in human and porcine leukocytes with half-maximal inhibition at 4.0 and 2.7 μmol/l, respectively. The underlying mechanism was found to be a cis-trans-isomerisation of leukotriene B4 to the 5S,12R-6-trans-isomer. 5-Hydroxy-eicosatetraenoic acid was also isomerised to the 8-trans-isomer. At higher concentrations, ebselen induces a dose-dependent decrease in the sum of total 5-lipoxygenase products with half-maximal inhibition at 30 μmol/l. Additionally, the effects of ebselen on human platelet 12-lipoxygenase and cyclooxygenase were investigated. Human platelet 12-lipoxygenase and cyclooxygenase were inhibited in a dose dependent manner with half-maximal inhibition at 20 μmol/l and 5 μmol/l, respectively. We suggest that suppression of leukotriene B4-formation by isomerisation to a biologically inactive compound represents a promising approach to the therapy of inflammation. |
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