deoxycholic-acid has been researched along with Hypercholesterolemia* in 11 studies
11 other study(ies) available for deoxycholic-acid and Hypercholesterolemia
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Effect of activation of liver X receptor alpha on cardiac & hepatic ABCC10 and SLC17A5 drug transporters in hypercholesterolemic rat model.
Liver x receptor α (LXRα) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. Oxysterols (endogenous oxidized cholesterol derivatives) are the most potent endogenous LXRα-agonist. LXRα has a direct impact on several members of drug transporter superfamilies; ATP-binding cassette (ABC) and solute linked carrier (SLC).. The current study aimed to investigate the effect of LXRα-activation by either endogenous oxysterols or a synthetic LXRα-agonist (LXRa) such as TO901317 on hepatic and cardiac gene expression of ABCC10 and SLC17A5 drug transporters in an experimentally hypercholesterolemic rat model.. 48 male rats were divided randomly into four groups (n = 12); control group rats received vehicle; hypercholesterolemic group (HCH group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks; (LXRa group) rats were fed standard pellet chow for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg; (HCH + LXRa group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg.. Our findings revealed that hypercholesterolemia and LXRa significantly activated LXRα to varying degrees in both hepatic and cardiac tissues with subsequent alteration of LXRα and ABCC10 gene expression. Whereas, SLC17A5 gene expression was primarily affected by elevated serum cholesterol level and unmediated via LXRα-activation.. Accordingly, it was concluded that ABCC10 is a specific LXRα-target gene and that LXRα autoregulates its own expression in rats. Topics: Animals; ATP-Binding Cassette Transporters; Cholesterol; Deoxycholic Acid; Hypercholesterolemia; Liver; Liver X Receptors; Male; Orphan Nuclear Receptors; Oxysterols; Rats | 2022 |
Amphotericin B lipid complex or amphotericin B multiple-dose administration to rabbits with elevated plasma cholesterol levels: pharmacokinetics in plasma and blood, plasma lipoprotein levels, distribution in tissues, and renal toxicities.
The purpose of the present study was to determine if a relationship exists between the plasma cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the pharmacokinetics of AmpB in plasma in hypercholesterolemic rabbits administered multiple doses of amphotericin B (AmB) deoxycholate (Doc-AmB) and AmB lipid complex (ABLC). After 7 days of administration of a cholesterol-enriched diet (0.50% [wt/vol]) or a regular rabbit diet, each rabbit was administered a single intravenous bolus of Doc-AmB (n = 8) or ABLC (n = 10) (1.0 mg/kg of body weight) daily for 7 consecutive days (a total of eight doses). Blood samples were obtained daily before and 24 h after the administration of each dose and serially thereafter following the administration of the last dose for the assessment of pharmacokinetics in plasma, kidney toxicity, plasma lipoprotein levels, and drug distribution in tissue. The pharmacokinetics of AmB in blood following the administration of ABLC were also determined in rabbits fed cholesterol-enriched and regular diets (n = 3 each group). Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total, low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) cholesterol levels in plasma compared with the levels in rabbits on a regular diet. No significant differences in total plasma triglyceride levels were observed. Significant increases in plasma creatinine levels were observed in rabbits fed a cholesterol-enriched diet (P < 0.05) and rabbits fed a regular diet (P < 0.05) when administered AmB. However, the magnitude of this increase was twofold greater in rabbits fed a regular diet than in rabbits fed a cholesterol-enriched diet. An increase in plasma creatinine levels was observed only in rabbits on a cholesterol-enriched diet administered ABLC. The pharmacokinetics of AmB were significantly altered in rabbits on a cholesterol-enriched diet administered Doc-AmB or ABLC compared to those in rabbits on a regular diet administered each of these compounds. The pharmacokinetics of AmB in blood were significantly different following ABLC administration but not following Doc-AmB administration in both rabbits fed cholesterol-enriched diets and rabbits fed regular diets compared to their corresponding pharmacokinetics in plasma. An increased percentage of AmB was recovered in the TRL fraction when Doc-AmB was administered to rabbits fed a cholesterol-enriched diet than when it was ad Topics: Amphotericin B; Animals; Antifungal Agents; Cholesterol; Creatinine; Deoxycholic Acid; Drug Combinations; Hypercholesterolemia; Kidney; Kinetics; Lipoproteins; Phosphatidylcholines; Phosphatidylglycerols; Rabbits; Tissue Distribution | 2001 |
Marked reduction in bile acid synthesis in cholesterol 7alpha-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia.
These studies used mice that were deficient in cholesterol 7alpha-hydroxylase to determine the effects of reduced bile acid synthesis on cholesterol homeostasis. In mice lacking this enzyme, bile acid synthesis was reduced from 8.3 to 3.4 micromol/day per 100 g body weight, the intestinal bile acid pool was decreased from 62.5 to 13.2 micromol/100 g bw, and the proportion of hyodeoxycholate, relative to cholate, in this pool was significantly increased. Associated with these changes, intestinal cholesterol absorption decreased from 37% to <1% while triacylglycerol absorption and animal weight gain remained essentially unaffected. The very low rate of cholesterol absorption could be corrected by feeding the mutant mice cholate, but not hyodeoxycholate. The reduction in sterol uptake across the intestine was associated with a 2-fold increase in cholesterol synthesis in the small bowel and liver and an increase in fecal neutral sterol excretion from 15.2 to 35.7 micromol/day per 100 g bw. The size of the cholesterol pools in the plasma, various organs and whole animal remained constant. Thus, under circumstances where the excretion of sterol as bile acids was markedly reduced, total cholesterol turnover actually increased from 164 to 239 mg/day per kg bw. This study demonstrates the complex interactions between bile acid and cholesterol metabolism and the dramatic effects of eliminating a single gene product; however, even though a major catabolic pathway was deleted, cholesterol balance across the animal was maintained. Topics: Animals; Bile Acids and Salts; Cholates; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Deoxycholic Acid; Hypercholesterolemia; Intestinal Absorption; Intestine, Small; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Specificity | 1998 |
Bile acid excretion and cholesterol 7 alpha-hydroxylase expression in hypercholesterolemia-resistant rabbits.
We have developed a partially inbred substrain of New Zealand white rabbits (CRT/mlo) that are resistant to the hypercholesterolemia that accompanies cholesterol feeding to normal rabbits. The plasma cholesterol concentration of normal rabbits increases dramatically from about 30 mg/dl to > 300 mg/dl after they are fed a 0.1% cholesterol-enriched diet for 3-4 months. Cholesterol-fed CRT/mlo animals, however, maintain a cholesterol level of about 30 mg/dl during the entire cholesterol feeding period. In addition to the low plasma cholesterol level, measurements of cellular cholesterol indicate that the hepatic cholesterol content of the cholesterol-fed resistant rabbit remains markedly lower than it does in normal animals fed the same diet. The only mechanism for removal of significant quantities of cholesterol carbon from the body is via the fecal excretion of cholesterol, neutral sterol metabolites, and bile acids. In comparison to the basal, low-cholesterol diet, we observed that cholesterol-fed resistant rabbits had increased excretion of lithocholic acid, while excretion of this bile acid by cholesterol-fed normal rabbit remained similar to basal diet levels. Deoxycholic acid excretion, the other main bile acid excreted in the feces of rabbits, was decreased in response to cholesterol challenge in animals with either resistant or normal phenotypes, but the decrease was significantly less in the resistant rabbits. Thus, the resistant rabbits excreted relatively more lithocholic and deoxycholic acid than did the cholesterol-fed normal rabbit. The difference in bile acid excretion was also manifest by a higher than normal level of cholesterol 7 alpha-hydroxylase activity and cholesterol 7 alpha-hydroxylase mRNA in the livers from resistant versus normal rabbits. As cholesterol 7 alpha-hydroxylase is the putative rate-limiting step of bile acid synthesis, we believe that the increased excretion of bile acids by resistant animals is due, at least in part, to increased levels of cholesterol 7 alpha-hydroxylase expression. Topics: Animals; Base Sequence; Bile Acids and Salts; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Deoxycholic Acid; DNA, Complementary; Feces; Female; Gene Expression; Hypercholesterolemia; Lithocholic Acid; Liver; Male; Molecular Sequence Data; Rabbits; Rats; RNA, Messenger; Sequence Homology, Nucleic Acid | 1993 |
Effect of cholestyramine in early weaning on later response to serum and fecal steroid levels and cholesterol 7 alpha-hydroxylase activity to high-cholesterol diet in ExHC rats.
Male ExHC (exogenous hypercholesterolemic) rats were either prematurely weaned at 17 days of age or allowed to nurse until 35 days of age. The prematurely weaned rats were either fed a diet containing cholestyramine or cholestyramine-free diet until 35 days of age. Cholestyramine supplementation markedly increased fecal bile acid excretion and modified the composition. After giving a stock diet for 7 weeks, all rats received a cholesterol-enriched diet for 9 weeks. The serum cholesterol level in later time was not affected by early dietary manipulation. The activity of hepatic cholesterol 7 alpha-hydroxylase and fecal bile acid excretion at the end of the cholesterol challenge decreased in the cholestyramine-pretreated group, when compared to the normally weaned group. Fecal excretion and the ratio of the secondary (deoxycholic and lithocholic acids) to the primary (cholic and chenodeoxycholic acids) bile acids significantly decreased in the early cholestyramine-treated group. These results suggest that a modification of bile acid metabolism in early life may strongly influence the hepatic and possibly colonic bile acid metabolism in later life, when challenged with a high-cholesterol diet. Topics: Animals; Bile Acids and Salts; Chenodeoxycholic Acid; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Cholestyramine Resin; Cholic Acid; Cholic Acids; Deoxycholic Acid; Feces; Hypercholesterolemia; Lithocholic Acid; Liver; Male; Rats; Rats, Inbred Strains; Steroid Hydroxylases; Weaning | 1990 |
Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats.
The effects of short-term treatment with orally-administered zinc sulphate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulphate (20 or 40 mg/kg, as zinc ion) for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free beta-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free beta-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol in the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulphate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free beta-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver. Topics: Animals; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Deoxycholic Acid; Hypercholesterolemia; Lipid Peroxides; Lipoproteins; Liver; Male; Malondialdehyde; Rats; Rats, Inbred Strains; Zinc | 1989 |
Correlative studies of the hypocholesterolemic effect of a highly activated charcoal.
We have carried out in vitro and animal studies to determine the cholesterol lowering efficacy of activated charcoals vs. cholestyramine. In the in vitro studies, we determined the adsorption capacity (Qm) of cholestyramine and activated charcoals for cholesterol in glacial acetic acid. Mean (+/- SD) Qm's (mg cholesterol adsorbed/gm dry sorbent) decreased in the order Super Char highly activated charcoal (277 +/- 121), Norit USP XX charcoal (33 +/- 10), Acta-Char charcoal (26 +/- 4), Mallinckrodt USP charcoal (26 +/- 10), Norit A charcoal (22 +/- 4) and cholestyramine (0). For the bile salt sodium desoxycholate in ammonia: sodium bicarbonate, pH 8.2, the Qm with cholestyramine was 4641 +/- 2669 and with Super Char was 2814 +/- 667 (p = 0.11). We then contrasted the effect of cholestyramine (1%, added to the diet) and Super Char (1% or 2%) on plasma cholesterol concentrations in rabbits made hypercholesterolemic with a diet containing casein. The percent reductions were 61 in one rabbit fed cholestyramine, 61 and 67 in two rabbits fed 1% Super Char, and 90 in one rabbit fed 2% Super Char. In WHHL homozygous rabbits, reductions in plasma cholesterol from pre-treatment and post-treatment levels, respectively, averaged 52% and 38% with 2% cholestyramine (2 animals), 70% and 43% with 2% Super Char (2 animals), and 70% and 63% with 4% Super Char (3 animals). The effectiveness of cholestyramine in animals that lack functional cellular receptors for low density lipoprotein was unexpected. Super Char charcoal appears to be an effective hypocholesterolemic agent, warranting study in man. Topics: Animals; Anticholesteremic Agents; Charcoal; Cholestyramine Resin; Deoxycholic Acid; Hypercholesterolemia; In Vitro Techniques; Rabbits | 1987 |
The effects of zinc sulphate on hypercholesterolaemia induced by cholesterol-choleate in rats.
The effects of zinc sulphate on cholesterol-choleate-induced hypercholesterolaemia were studied in rats. Zinc sulphate (20 or 40 mg/kg, p.o. once daily for 5 days) administration, which raised serum zinc levels, significantly increased bile acid secretion and lowered high-density lipoprotein-cholesterol (HDL-C) levels in the serum. Cholesterol-choleate, given by the same route and schedule, markedly elevated serum total cholesterol level, but decreased serum HDL-C concentration. Bile acid in serum and in bile was also increased, but these changes were inhibited by zinc sulphate pretreatment. Zinc sulphate also worsened the decrease in HDL-C and slightly prolonged the elevation in total cholesterol produced by cholesterol-choleate administration. It is concluded that the moderate increase in serum total cholesterol level by zinc sulphate could be due to inhibition of hepatic metabolism of cholesterol to bile acid. The specific action of zinc ions on HDL-C metabolism is discussed. Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Cholesterol, HDL; Deoxycholic Acid; Hypercholesterolemia; Male; Rats; Rats, Inbred Strains; Sulfates; Zinc; Zinc Sulfate | 1985 |
Some effects of deoxycholate administration on the metabolism of cholesterol in man.
Hypercholesterolemic subjects in a metabolic ward were kept under uniform dietary conditions until constant levels of serum cholesterol were observed. Oral dosage with deoxycholate (1.5 to 3 g daily for a period of 4 to 10 weeks) resulted in a marked reduction of serum cholesterol concentration. Studies with 14C-labeled cholesterol demonstrated that deoxycholate administration decreased absorption of cholesterol from the human intestinal tract. In these subjects, the turnover rate of serum cholesterol was more rapid during therapy with deoxycholate than during control periods. Deoxycholate appeared to influence the intestinal flora as assessed indirectly by analysis of the types of neutral sterols eliminated with the feces. Decreased synthesis of cholesterol during deoxycholate administration uas demonstrated in a study with 14C-mevalonate. It is concluded that deoxycholic acid can have an important role in the regulation of cholesterol metabolism in humans. Topics: Adult; Aged; Anticholesteremic Agents; Cholestanol; Cholestanols; Cholesterol; Cholesterol Esters; Deoxycholic Acid; Feces; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Intestines; Male; Middle Aged; Sterols | 1979 |
[Current concepts on dietary fibers. Their role in human pathology].
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 | 1976 |
Hypercholesterolemic effect in the female rat of egg yolk versus crystalline cholesterol dissolved in lard.
Topics: Animal Nutritional Physiological Phenomena; Animals; Bile Acids and Salts; Carbon Radioisotopes; Cholesterol; Cholesterol, Dietary; Cholic Acids; Deoxycholic Acid; Dietary Fats; Dietary Proteins; Egg Yolk; Fatty Acids; Feces; Female; Hypercholesterolemia; Lithocholic Acid; Liver; Organ Size; Rats; Steroids | 1973 |