Inhibition of lipoxygenase products by retinoids in human blood cells.
Arotinoids, third generation retinoids, inhibited significantly 12-lipoxygenase in platelets and 5-lipoxygenase in human neutrophils. The doses required for inhibition of 12-lipoxygenase in platelets were as low as 1 pM and of 5-lipoxygenase in neutrophils as low as 100 pM. No cytotoxicity was observed in neutrophils at concentrations used, as assayed by exclusion of trypan blue dye. In contrast to various studies reported in the literature, arotinoids used inhibited ionophore-induced arachidonic acid (AA) release in platelets and neutrophils of humans. The doses required for 50% inhibition of AA release were between 10 pM and 75 nM for platelets and between 1 and 50 nM for neutrophils. The data suggest that arotinoids are excellent dual inhibitors of cyclooxygenase and lipoxygenase pathways of AA metabolism. The mechanism for inhibition of eicosanoids lies apparently in the inhibition of AA deacylation from phospholipid membrane. It cannot, however, be ruled out that the accumulation of AA results from arotinoid-induced stimulation of reacylation of AA into the phospholipid membrane.
Nigam
S
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Department of Gynecological Endocrinology, University Medical Center Steglitz, Free University of Berlin, FRG.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001565:Benzoates / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology*
D001565:Benzoates; D006893:Hydroxyeicosatetraenoic Acids; D012176:Retinoids; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C034814:ethyl-p-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl)benzoic acid; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; C045042:Ro 15-1570