Differential effects of malotilate on 5-, 12- and 15-lipoxygenase in human ascites cells.
Macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 and 5-monohydroxyeicosatetraenoic acid. The cyclooxygenase products 6-keto-PGF1 alpha and thromboxane B2 were the most important prostaglandin-like substances. Malotilate, an anti-fibrotic substance, selectively inhibited the 5-lipoxygenase, whereas both the 12- and the 15-lipoxygenase pathways were stimulated. The effects of malotilate on eicosanoid production differ from those of known lipoxygenase inhibitors. Such differential effects have not been reported previously.
Zijlstra
F J
FJ
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Wilson
J H
JH
Vermeer
M A
MA
Ouwendijk
R J
RJ
Vincent
J E
JE
D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008314:Malonates / Q000494:pharmacology*
D008314:Malonates; D007975:Leukotriene B4; D001091:Arachidonate Lipoxygenases; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate