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Effects of alpha-tocopherol, its carboxylic acid chromane compound and two novel antioxidant isoflavanones on prostaglandin H synthase activity and autodeactivation

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Summary

The natural antioxidant alpha-tocopherol has repeatedly been described to inhibit platelet aggregation and thromboxane formation, whereas its influence on prostaglandin H synthase in vivo and in vitro is a matter of controversy. In the present study the effects of different antioxidative compounds on ram vesicular gland microsomal prostaglandin H synthase activity were investigated in vitro: d,l-alpha-tocopherol, its carboxylic acid chromane compound (Trolox), phytol, alpha-tocopherolacetate and two novel antioxidative isoflavanones, obtained by methylation and/or hydrogenation of naturally occurring isoflavones from fermented soybeans (6,7-dihydroxy-4′-methoxyisoflavanone and 6,7,4′-trihydroxyisoflavanone). Alpha-tocopherol,-acetate and phytol revealed no significant influence on the enzyme activity when applied in concentrations up to 1 mM. Trolox (100–1000 μmol/l) and the two isoflavanones (5–50 and 10–100 μmol/l) dose-dependently augmented the initial rate of oxygen consumption and the total oxygen uptake during prostaglandin H synthase incubation with arachidonic acid (AA). In parallel, these compounds increased the formation of prostaglandin E2 and F2 alpha from 14C-labelled AA, and they markedly protected the prostaglandin H synthase from rapid autodeactivation as revealed by repetitive application of AA in small doses. We suggest that these compounds serve as cosubstrates to which the oxidizing equivalents are transferred which arise during the hydroperoxidase reaction of the enzyme.

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Abbreviations

AA:

arachidonic acid

PG:

prostaglandin

IC50 :

concentration for 50% inhibition

v i :

initial rate of oxygen consumption

Trolox:

6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid

pO2 :

oxygen tension in solution

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Authors and Affiliations

  1. Division of Clinical Pathophysiology and Experimental Medicine, Department of Internal Medicine, Department of Clinical Chemistry and Biochemistry, Justus-Liebig-University, Klinikstrasse 36, D-6300, Giessen, Federal Republic of Germany

    Werner Seeger, Ulrike Moser & Ladislaus Roka

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  1. Werner Seeger
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  2. Ulrike Moser
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  3. Ladislaus Roka
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Send offprint requests to W. Seeger at the above address

This manuscript includes parts of the thesis of U. Moser

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Seeger, W., Moser, U. & Roka, L. Effects of alpha-tocopherol, its carboxylic acid chromane compound and two novel antioxidant isoflavanones on prostaglandin H synthase activity and autodeactivation. Naunyn-Schmiedeberg's Arch Pharmacol 338, 74–81 (1988). https://doi.org/10.1007/BF00168815

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  • DOI: https://doi.org/10.1007/BF00168815

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