Modulation of arachidonic acid metabolism by phenols: relation to positions of hydroxyl groups and peroxyl radical scavenging properties.
We have shown earlier that catecholamines have opposite regulative effects on prostaglandin (PG)E2 and leukotriene (LT)B4 formation with a receptor-independent mechanism in human polymorphonuclear leukocytes (PMNs) and whole blood. To shed further light on the mechanisms involved and structure-action relationship, we tested the effects of phenols (catechol, hydroquinone, phenol, and resorcinol) on the synthesis of PGE2 and LTB4 in human A23187-stimulated PMNs. To study the mechanism of how phenols influence PGE2 and LTB4 synthesis, their peroxyl radical-scavenging properties were analyzed. In general, low concentrations of phenols stimulated (catechol > hydroquinone >> phenol) and high concentrations inhibited (resorcinol > catechol > hydroquinone > phenol) PGE2 formation. Resorcinol was different from the other phenols: It did not stimulate PGE2 synthesis at all, but it was effective inhibitor at high concentrations. Phenols had only an inhibitory effect on LTB4 formation (catechol = hydroquinone >> phenol > resorcinol). The order of both stochiometric factors and reactivities of phenols for scavenging peroxyl radicals was catechol > hydroquinone > resorcinol >> phenol. According to these results, phenols having hydroxyl groups in ortho- or paraposition have the greatest stimulative effect on PGE2 synthesis, the highest inhibitory action on LTB4 synthesis, and are good antioxidants. Resorcinol, having hydroxyl groups in the metaposition, behaves differently. It neither stimulates PGE2 nor inhibits LTB4 formation, but it is the most potent inhibitor of PGE2 formation. In spite of resorcinol's two hydroxyl groups, it mimics as an antioxidant phenol more than catechol and hydroquinone.
Alanko
J
J
Department of Biomedical Sciences, University of Tampere, Finland.
Riutta
A
A
Mucha
I
I
Vapaatalo
H
H
Metsä-Ketelä
T
T
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D010545:Peroxides; D010636:Phenols; D007975:Leukotriene B4; D016718:Arachidonic Acid; C049375:perhydroxyl radical; D015232:Dinoprostone