Comparative study of cardioprotective and antiradical activity of estrogens and their nitro derivatives

Abstract

Cardioprotective and antiradical activities of estrogens and their nitro derivatives are compared. Antiradical activity was observed in estradiol, ethanol estradiol, and estradiol nitrate, but not in nystranol, which exhibited antiradical properties only after acid hydrolysis. The data obtained on hearts from rats with experimental myocardial infarction show that estrogens and their nitro derivatives restrict the area of myocardial infarction due to antiischemic and/or antinecrotic activities. Key Words: antiradical activity; nitro estrogens; experimental myocardial infarctionConsiderable attention is now focused on clinical application of estrogens and their synthetic analogs for preventing and treating cardiovascular diseases not only in women, but also in men [2,6].There is evidence that natural estrogen 17~-estradiol possesses a cardioprotective effect and restricts the area of myocardial infarction (MI) [5].In this connection it is of interest to study modified synthetic estrogens carrying an ONO 2 group, potential donor of nitric oxide. These derivatives are nystranol and estradiol nitrate.Chemical structure of nystranol and estradiol nitrate suggests that they could affect the cardiovascular system more efficiently than classical estrogens due to generation of bioactive NO group.Natural estrogens have a pronounced antiradical activity [3]. There are no such data on the nitro estrogens. Bearing in mind the important role of lipid peroxidation in the pathogenesis of MI, examination of estrogen nitro derivatives for potential antiradical activity would have a practical resonance.Our aim was to compare cardioprotective and antiradical activity of estrogens and their nitro derivatives MATERIALS AND METHODSExperiments were carried out on outbred albino rats of both sexes weighing 200-300 g. Estradiol (17~-estradiol), ethanol estradiol, nystranol (9t~-oxy-1 l~-nitroxyethynylestradiol diacetate), and estradiol nitrate (17 estradiol nitrate) were injected intraperitoneally in a dose of 10 mg/kg (in 20% ethanol) one hour before coronary occlusion. MI was provoked by ligating the descendant branch of the left coronary artery immediately below the auricula [7].The effect of steroids on the size of experimental MI was assessed after 4-h coronary occlusion.Estrogens and their nitro derivatives were tested for antiradical activity in the reaction of azo-bis-isobutyronitrile-induced oxidation of isopropylbenzene (cumol) as described elsewhere [9,10]. Test substance was added to cumol in a concentration of 5• -3 M. Nystranol was hydrolyzed with 0.1 M HCI. Oxidation kinetics was assessed by oxygen consumption measured using a gasometric setup. To determine the rate constant of interaction of the inhibitor with cumol peroxide radicals (K7), the kinetic curve of oxygen absorption was plotted in the semilogarithmic scale convert-0007-4888/99/0010-1009522.00 9Kluwer Academic/Plenum Publishers

Antiarrhythmic properties of estrogens

“…Estradiol valerate is used in clinical practice as an estrogen substitute. Estradiol nitrate is a new promising donor of NO [5].Here we compared antiarrhythmic activity of female sex hormones estrone and estriol with that of estradiol valerate and commonly used antiarrhythmics lidocaine and Ethmozine. …”

“…Estradiol valerate is used in clinical practice as an estrogen substitute. Estradiol nitrate is a new promising donor of NO [5].…”