deoxycholic-acid and Arteriosclerosis

We examined the effect of hyodeoxycholic acid (HDCA) on plasma cholesterol levels and atherosclerosis in mice. In wild-type C57BL/6 mice, feeding increasing amounts of HDCA resulted in i) progressive decrease in dietary cholesterol absorption, ii) increased concentrations of HDCA in the gallbladder bile, iii) decreased liver cholesterol content, iv) increased liver cholesterol synthesis, and v) increased plasma concentrations of HDCA. In C57BL/6 LDL-receptor knockouts (LDLR-KO) the addition of HDCA to chow and a 0.5% cholesterol diet decreased their total plasma cholesterol levels by 21% and 62%, respectively, because of a decrease in VLDL and LDL cholesterol. Turnover studies showed that HDCA has no effect on VLDL removal from plasma. Furthermore, the addition of HDCA to chow- and 0.5% cholesterol-fed LDLR-KO mice decreased the aortic root atherosclerosis lesion area by 50% and 80%, respectively. Finally, we tested the effect of HDCA on intestinal tumor formation. Feeding C57BL/6 ApcMin mice with HDCA did not affect the number of tumors but decreased the tumor volume in these animals. These results suggest that HDCA might have beneficial effects in the treatment of increased plasma cholesterol levels and atherosclerosis.

Topics: Absorption; Animals; Arteriosclerosis; Bile; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Cholesterol, VLDL; Deoxycholic Acid; Hydroxymethylglutaryl CoA Reductases; Intestinal Neoplasms; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL

Topics: Adult; Arteriosclerosis; Cholestasis, Intrahepatic; Chronic Disease; Deoxycholic Acid; Female; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Risk Factors; Ursodeoxycholic Acid

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Cerebral Infarction; Cholesterol; Deoxycholic Acid; Female; Humans; Male; Middle Aged; Ursodeoxycholic Acid

Bile flow and biliary bile acids were analyzed in arteriolipidosis-prone rats (ALR), the hypertensive model for lipidemic arterial lesions with reactive hypercholesterolemia and compared to those in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Bile flow and bile acid secretion decreased in the order of WKY, SHR and ALR. When labelled cholesterol was given intraperitoneally, the biliary radioactivity secretion was significantly slow in ALR in comparison with that in WKY. The decay of radioactive cholesterol in serum after the injection was also delayed in ALR. Our data suggest that the abnormality in bile flow, biliary bile acid secretion and/or cholesterol turnover to bile acids may be pathogenically related to reactive hypercholesterolemia noted in the ALR.

Topics: Animals; Arteriosclerosis; Bile Acids and Salts; Body Weight; Cholesterol; Cholic Acids; Deoxycholic Acid; Hypertension; Lipidoses; Liver; Male; Rats; Rats, Inbred Strains; Triglycerides

Topics: Absorption; Arteriosclerosis; Bile Acids and Salts; Cellulose; Cholelithiasis; Cholesterol; Colonic Neoplasms; Constipation; Deoxycholic Acid; Dietary Fiber; Humans; Hypercholesterolemia; Intestinal Absorption; Lipid Metabolism; Lithocholic Acid; Pectins; Water