[The effect of ximedon on cholesterol metabolism and experimental atherosclerosis in rabbits]

The effects produced by the two pyrimidine derivatives pyridinol carbamate (parmidine) and xymedon on cholesterol metabolism and experimental atherosclerosis were comparatively studied in rabbits. The rabbits were fed either a chow containing cholesterol (200 mg/kg body weight) or the same diet also containing xymedon (30 mg/kg body weight) or pyridinol carbamate (30 mg/kg body weight). Total plasma cholesterol showed 5.5- and 4.7-fold increases in the rabbits receiving only cholesterol or cholesterol + pyridinol carbamate, respectively, as compared with that in the animals on a standard laboratory chow. In the rabbits given cholesterol+xymedon, cholesterol levels were 24% less than that in the animals taking cholesterol alone. In these animals, the aortic atherosclerotic damage index (ADI) was equal to 24.1%, which was 1.8-fold less than that in the cholesterol-fed rabbits. In the rabbits given cholesterol+pyridinol carbamate, ADI was decreased by 1.7 times, but it did not differ from that in the hypocholesterolemic rabbits. At the same time xymidone and pyridinol carbamate reduced the hepatic levels of total and esterified cholesterol. To elucidate the mechanism of action of xymedon, it was studied for effects on cholesterol metabolism in cultured rabbit hepatocytes and murine macrophage J774. Xymedon did not alter the esterification and other parameters of cholesterol metabolism in the cultured hepatocytes. It is suggested that the hypocholesterolemic effect was realized at the level of intestinal rather than hepatic cholesterol metabolic changes. The investigations made on the murine macrophage J744 showed that xymedone reduced cholesterol esterification in macrophages, evidently by inhibiting the activity of the enzyme acyl-CoA: cholesterol acyltransferase. The anti-atherosclerotic effect of xymedon seems to result from reductions in plasma cholesterol levels and cholesterol esterification in blood vascular cells.