Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids

Pearlman, B.J.; Bonorris, George; Phillips, M. James; Chung, A.; Vimadalal, Shirin; Marks, Jay W.; Schoenfield, Leslie J.

doi:10.1016/0016-5085(79)90213-0

Cited by 63 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore studied the effect of high-dose ethinylestradiol on biliary output of cholesterol with the aim to separate effects mediated by alteration in bile acid metabolism from more direct effects on the secretory process for cholesterol into bile. The Syrian Golden hamster was choosen as animal model, since it has the same major bile acid species in a similar distribution as man (15,16), also has a gallbladder and appears to have similarities in total body cholesterol metabolism with man (17). veterinary commission.…”

Section: Ethinylestradiol Stimulates a Biliary Cholesterol-phospholipidmentioning

confidence: 99%

Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Berr¹,

Stellaard²,

Goetz³

et al. 1988

Hepatology

View full text Add to dashboard Cite

The mechanism of ethinylestradiol-induced biliary secretion of excess cholesterol, a potential causative factor of cholesterol gallstones, is not yet known. It might be related to altered bile acid metabolism, since the rate of cholesterol and phospholipid secreted into bile is thought to be influenced by the hydrophobicity of the bile acid species secreted. We therefore studied the effect of ethinylestradiol on bile acid metabolism and on secretory relationships between taurocholate and cholesterol/phospholipids in bile. Litter-matched Syrian female hamsters (80 to 100 gm body weight) were injected subcutaneously with either 0.2 ml per day corn oil (controls) or a pharmacologic dose of 5 mg per kg per day ethinylestradiol in corn oil (EE-hamsters; n = 6) for 5 days. On Day 6, bile was collected for 60 min (basal secretory rate) via a bile duct fistula after exclusion of the gallbladder. Then, a graded infusion of taurocholate was given for 110 to 130 min. Secretory rates (nmoles.min-1.-1 liver) for bile acids, cholesterol and phospholipids were determined and their mutual "linkage coefficients" (nmoles of secretory increment per 1 nmole of bile acid secreted) calculated by linear regression analysis. EE-hamsters had higher (p less than 0.02) basal secretory rates of cholesterol (0.71 +/- 0.21 vs. 0.45 +/- 0.10) and phospholipids (5.74 +/- 1.04 vs. 4.21 +/- 0.73) than controls at comparable bile flow and bile salt secretion rates. Cholic acid pool size and the fractional composition of bile acid species in bile were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Ethinylestradiol Stimulates a Biliary Cholesterol-phospholipidmentioning

confidence: 99%

Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Berr¹,

Stellaard²,

Goetz³

et al. 1988

Hepatology

View full text Add to dashboard Cite

show abstract

“…Ho (1976) examined biliary CH in several species like hens, rabbits, rats, hamsters, ground squirrels, and prairie dogs fed a high CH diet over 4 weeks. Gallstone formation after feeding similar diets was observed in squirrel monkeys (Osuga and Portman 1971) and in prairie dogs (Den Besten et al 1974), whereas additional drugs like dehydrocholic acid (Besan~on et al 1965), cholestyramine (Schoenfield and Sj6vall 1966), cholic acid (Tepperman et al 1964) or hormones (Pearlman et al 1979) had to be administered to induce gallstones in other species. The more than tenfold rise of biliary CH in tupaias is the highest increase ever reported for various species under similar feeding conditions.…”

Section: Discussionmentioning

confidence: 97%

Tupaias (tree shrews) — A new animal model for gallstone research

1980

View full text Add to dashboard Cite

Metabolic reactions to the increased intake of cholesterol (CH)were studied in ten tupaias (Tupaia belangeri Baf:BIAS, tree shrews), fed a lithogenic diet containing 20% fat and 2% CH. The feeding period was 4 months. Twelve animals on standard diet served as controls.The CH content was determined in serum, bile, liver, heart, skin, kidney, muscle, jejunum, ileum, and in the total body. In vitro synthesis rates of CH were measured in the liver and in different parts of the gut.In animals fed the lithogenic diet, serum CH values exceeded those of controls by a factor of 2. However, of all organs examined only the liver showed a rise in the CH content. In hepatic bile, CH values were 14 times higher than in the controls.Intrahepatic synthesis of CH was suppressed to 7% of the rate in animals on standard diet. In the jejunum, CH synthesis rates were 44%, and in the ileum 15% of those determined in controls.It is concluded that the administration of a high CH diet induces a feedback mechanism which lowers the production of CH in the liver and small intestine. However, this adaptation does not prevent the rise of CH in serum, liver, and bile which finally results in the formation of gallstones in the gallbladder.Chenodeoxycholic acid (CDCA), added to the lithogenic diet in a daily dose of 20mg/kg body weight (BW) in five animals, produced an additional significant increase in the hepatic CH content compared to the animals fed the lithogenic diet without CDCA. Other parameters did not differ between the two groups fed the lithogenic diet with and without CDCA.

show abstract

“…Diets supplemented with cholesterol have shown to produce lithogenic bile and gallstones in experimental animals including prairie dogs, squirrel monkeys and hamsters (DenBesten et al. 1974; Pearlman et al. 1979), rats and mice (Hussain & Chandrasekhara 1992, 1994; Vidyashankar et al.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have reported hypocholesterolemic influence of various dietary components like fibre (Anderson et al 1992;Jenkins et al 1993) and spices -Red pepper, turmeric, fenugreek, onion and garlic have been used in several animal models (Srinivasan et al 2004); particularly fenugreek seeds (Reddy & Srinivasan 2009a,b) and onion in mice (Vidyashankar et al 2009). Diets supplemented with cholesterol have shown to produce lithogenic bile and gallstones in experimental animals including prairie dogs, squirrel monkeys and hamsters (Den-Besten et al 1974;Pearlman et al 1979), rats and mice (Hussain & Chandrasekhara 1992, 1994Vidyashankar et al 2009Vidyashankar et al , 2010. Continuous feeding of HCD increased cholesterol content and hence elevated the cholesterol ⁄ phos-pholipid ratio, cholesterol ⁄ BAs ratio and CSI in bile, which eventually resulted in cholesterol crystallization.…”

Section: Discussionmentioning

confidence: 99%

Dietary fenugreek and onion attenuate cholesterol gallstone formation in lithogenic diet–fed mice

Reddy

Srinivasan

2011

Int J Experimental Path

View full text Add to dashboard Cite

An animal study was conducted to evaluate the antilithogenic effect of a combination of dietary fenugreek seeds and onion. Lithogenic conditions were induced in mice by feeding them a high (0.5%) cholesterol diet (HCD) for 10 weeks. Fenugreek (12%) and onion (2%) were included individually and in combination in this HCD. Fenugreek, onion and their combination reduced the incidence of cholesterol gallstones by 75%, 27% and 76%, respectively, with attendant reduction in total cholesterol content by 38-42%, 50-72% and 61-80% in serum, liver and bile respectively. Consequently, the cholesterol/phospholipid ratio was reduced significantly in serum, liver and bile. The cholesterol saturation index of bile was reduced from 4.14 to 1.38 by the combination of fenugreek and onion and to 2.33 by onion alone. The phospholipid and bile acid contents of the bile were also increased. Changes in the hepatic enzyme activities (3-hydroxy-3-methylglutaryl Coenzyme A reductase, cholesterol-7α-hydroxylase and cholesterol-27-hydroxylase) induced by HCD were countered by fenugreek, onion and their combination. Hepatic lipid peroxides were reduced by 19-22% and 39-45% with fenugreek, onion and their combination included in the diet along with the HCD. Increased accumulation of fat in the liver and inflammation of the gallbladder membrane produced by HCD were reduced by fenugreek, onion and their combination. The antilithogenic influence was highest with fenugreek alone, and the presence of onion along with it did not further increase this effect. There was also no additive effect of the two spices in the recovery of antioxidant molecules or in the antioxidant enzyme activities.

show abstract

Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids

Cited by 63 publications

References 18 publications

Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Ethinylestradiol stimulates a biliary cholesterol-phospholipid cosecretion mechanism in the hamster

Tupaias (tree shrews) — A new animal model for gallstone research

Dietary fenugreek and onion attenuate cholesterol gallstone formation in lithogenic diet–fed mice

Contact Info

Product

Resources

About