ROLE OF HYDROXYL RADICAL SCAVENGERS DIMETHYL-SULFOXIDE, ALCOHOLS AND METHIONAL IN INHIBITION OF PROSTAGLANDIN BIOSYNTHESIS

Prostaglandin biosynthesis from eicosa-8,11,14-trienoic acid in microsomes from bovine seminal vesicles is inhibited by relatively high concentrations of hydroxyl radical scavengers: dimethyl sulfoxide, n- and t-butanol, and methional. Methional is a more effective scavenger than t-butanol and dimethyl sulfoxide, 2 compounds which are more miscible with H2O than methional. The synthesis of both PGE [prostaglandin E] and PGF is inhibited with incubation systems that promote PGE formation and with incubation systems that promote PGF formation. Dimethyl sulfoxide and methional inhibit arachidonic acid-induced platelet aggregation, a reaction involving endoperoxide biosynthesis. The H2O soluble alcohol, ethanol, stimulates PGF biosynthesis when it is added in the same concentration range as t-butanol. Thus hydroxyl radical scavengers inhibit biosynthesis when their effective concentrations are high and stimulate biosynthesis when their effective concentrations are low. The results of this study and other studies where low concentrations of hydroxyl radical scavengers stimulate both PG biosynthesis and lipid peroxidation are consistent with a mechanism involving the hydroxyl radical both in the generation of singlet O2 and the elimination of H2O2.