Anthralin (1,8-dihydroxyanthrone) is a potent inhibitor of leukotriene production and LTB4-omega oxidation by human neutrophils.
The effect of anthralin and its oxidation products danthrone and anthralin-dimer on the production of 5-lipoxygenase products (5-HETE, leukotriene B4, omega-oxidized LTB4) by Ca-ionophore A 23187-stimulated human neutrophils has been studied in vitro. Anthralin exhibited dose-dependent inhibitory activity showing 50% inhibition at 7 microM with 10(7) neutrophils. Inhibitory effects strongly depended upon cell densities and maximal inhibition occurred at low cell concentrations, whereas inhibitory rates of anthralin were low at high cell densities. Inhibition of leukotriene production persisted after washing of anthralin-treated neutrophils. Also, with increasing amounts of arachidonic acid as substrate only slight changes of inhibitory activity were detected, indicating a noncompetitive way of action. In addition to the inhibition of leukotriene-production, the formation of omega-OH-LTB4 from LTB4 as well as omega-COOH-LTB4 from omega-OH-LTB4 was inhibited with IC50 (half maximum inhibition concentration) near 4.4 microM and 2.2 microM, respectively. In contrast to anthralin, both metabolites--danthrone as well as anthralin-dimer--did not show any effect on leukotriene production and omega-oxidation even at high concentrations (up to 70 microM and 44 microM, respectively).
D000875:Anthralin / Q000494:pharmacology*; D000880:Anthraquinones / Q000494:pharmacology; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction
D000880:Anthraquinones; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D000875:Anthralin; C004315:danthron