Antiatherogenic action of eicosapentaenoic acid (EPA) in multiple oral doses.
The possible antiatherogenic action of eicosapentaenoic acid (EPA) was pharmacologically investigated using purified and ethylesterified fish oil containing 75% EPA (EPA-E) in multiple oral doses in rats and rabbits. EPA-E showed dose-dependent prevention of thrombus formation in a vascular shunt or sudden death caused by arachidonic acid injection in rats. EPA-E in daily doses ranging from 3 to 30 mg/kg slightly altered platelet aggregability and prostacyclin-like activity generated from arterial ring preparations of rats, but these alterations were not statistically significant. Further, EPA-E showed no effect on blood viscosity of rats. In cholesterol-fed rabbits, EPA-E in daily doses of 10 and 30 mg/kg moderately lowered the levels of plasma cholesterol, beta-lipoprotein, triglyceride and phospholipid, but these changes showed neither dose-dependency nor time-dependency. In this experiment, EPA-E moderately altered atherogenic plaque formation and platelet aggregability, but these alterations were not statistically significant. EPA-E showed no effect on prostacyclin-like activity generated from arterial ring preparations and blood viscosity of cholesterol-fed rabbits. It is, therefore, proposed that the antithrombotic action of EPA-E may be partially related to its effects on platelet aggregability and prostacyclin generation, but the major mechanism remains unclear.
D000284:Administration, Oral; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity; D001161:Arteriosclerosis / Q000517:prevention & control*; D001809:Blood Viscosity / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D011464:Epoprostenol / Q000096:biosynthesis; D000960:Hypolipidemic Agents; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D000960:Hypolipidemic Agents; D016718:Arachidonic Acid; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol