Modulation of arachidonic acid metabolism by phenols: relation to their structure and antioxidant/prooxidant properties.
The effects of substituted catechols (3-methylcatechol, 4-methylcatechol, 4-nitrocatechol, and guaiacol) and trihydroxybenzenes (pyrogallol, propyl gallate, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) on the synthesis of prostaglandin (PG)E2 and leukotriene (LT)B4 were tested in human A23187-stimulated polymorphonuclear leukocytes. The effects were related to their peroxyl-radical-scavenging (antioxidant), superoxide-scavenging (antioxidant), and superoxide-generating (prooxidant) properties. In general, compounds with hydroxyl groups in the ortho position increased PGE2/LTB4 ratio, and compounds with hydroxyl groups in the meta position decreased PGE2/LTB4 ratio. Catechols, which have hydroxyl groups in the ortho position, were the most potent peroxyl radical and superoxide anion scavengers. Trihydroxybenzenes (pyrogallol, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) generated superoxide, whereas dihydroxybenzenes did not. Thus, the positions and number of hydroxyl groups seem to be the most important properties determining the action of phenolic compounds on PGE2/LTB4 ratio and their antioxidant/prooxidant activities.
Alanko
J
J
Department of Internal Medicine, Tampere University Hospital, Finland. bljual@uta.fi
Riutta
A
A
Holm
P
P
Mucha
I
I
Vapaatalo
H
H
Metsä-Ketelä
T
T
D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry* / Q000494:pharmacology*; D010545:Peroxides / Q000378:metabolism; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D002396:Catechols; D016166:Free Radical Scavengers; D007476:Ionophores; D016877:Oxidants; D010545:Peroxides; D010636:Phenols; D013481:Superoxides; D007975:Leukotriene B4; D016718:Arachidonic Acid; C049375:perhydroxyl radical; D000001:Calcimycin; D015232:Dinoprostone