Abstract
Summary Hypocholesterolemic and anti-atherosclerotic effects of 2-methoxymethyl-17α-methylestradiol-3-methylether (P-5780) have been studied on the Triton-induced hyperlipidemic rats, cholesterol-fed rats and rabbits. (1) Prevention of hyperlipidemia caused by Triton was partly observed in rats by the pretreatment of a moderate dose of P-5780. (2) In both sexes of cholesterol and cholate-fed rats, P-5780 exerted a hypocholesterolemic effect, improved the plasma C/P ratio and partly prevented the accumulation of aortic total lipids and cholesterol without any sign of estrogenicity at the doses employed. (3) P-5780 revealed a prophylactic effect on the aortic atherosclerosis in both sexes of cholesterol and corn oil-fed rabbits without manifestation of estrogenic activity. The compound reduced cholesterol deposition in aorta, liver and adrenals, and improved the plasma C/P ratio but did not suppress the incidence of coronary atherosclerosis and hypercholesterolemia. In these 59 rabbits with or without P-5780, regression coefficients between level of plasma cholesterol and aortic atherosclerosis were not significant statistically. In the control group of cholesterol-fed rabbits, no significant correlation was obtained between the degree of aortic atherosclerosis and the other factors, such as coronary lesions, blood pressure and cholesterol-deposition in aorta, liver, adrenals and plasma. Treatment with P-5780 was accompanied by a significant correlation between the degree of aortic atherosclerosis and factors as coronary lesions and cholesterol concentrations in plasma and aorta. (4) In the regression experiment with aortic atherosclerotic rabbits, P-5780, administered after cessation of cholesterol feeding, did not influence the regression of aortic atheromata and depletion of cholesterol in plasma and tissues.
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