Antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 in cholesterol-fed rabbits with thyroid inhibition

Climacteric. 2001 Mar;4(1):49-57.

Abstract

Objective: The aim of this study was to investigate the antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 (estra-1,3,5(10),8-tetraene-3, 17 alpha-diol), having a non-feminizing effect and high antioxidant potential, in male rabbits.

Experimental design: Male White-Russian rabbits weighing 2.1-2.6 kg were fed either a standard or a high-cholesterol (200 mg/kg) diet, with thyroid function-inhibiting thiouracil (20 mg/kg) combined with cholic acid (40 mg/kg) administered daily in sunflower oil for 3 months. During the last month of the study, estrogens were administered by gavage at a dose of 0.02 or 0.1 mg/kg.

Results and conclusions: All three estrogens exerted remarkable antiatherosclerotic effects. Decreases in serum and aortic-wall lipid parameters and the index of atherogenicity were dependent on estrogen dose. Morphological evaluation of the aortic wall (height of plaques, size of plaque relative to aortic half-circumference) showed only weak therapeutic effects with all three estrogens. It is an open question whether the treatment period was too short to reverse the above changes. On the other hand, the data clearly suggest that 17 alpha-estradiol and J811 offer new perspectives for the prevention of atherosclerosis in men, which is similar to that found with 17 beta-estradiol in women.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / pharmacology*
  • Antithyroid Agents
  • Arteriosclerosis / blood
  • Arteriosclerosis / etiology
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control*
  • Cholesterol, HDL / blood
  • Diet, Atherogenic
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry
  • Estradiol / pharmacology*
  • Free Radical Scavengers / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / pathology
  • Hypercholesterolemia / prevention & control*
  • Male
  • Rabbits
  • Random Allocation
  • Sex Characteristics
  • Thiouracil

Substances

  • Anticholesteremic Agents
  • Antithyroid Agents
  • Cholesterol, HDL
  • Free Radical Scavengers
  • J811 scavestrogen
  • Estradiol
  • Thiouracil