Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment

Suckling, Keith E.; Benson, G. Martin; Bond, Brian; Gee, Andrew; Glen, A.I.M.; Haynes, Claire; Jackson, Brian

doi:10.1016/0021-9150(91)90059-c

Cited by 111 publications

(47 citation statements)

References 14 publications

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“…One potential problem is that, unless samples are initially subjected to treatment with a reducing agent followed by rigorous hydrolysis conditions of the kind applied here, their bile acid content may be underestimated because of the presence of a keto group or various ester linkages at the 3 position on the steroid ring. 41,50 This method might also underestimate total bile acid content to the extent that 3b- terol. These data were derived from the study described in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…51,66 While no attempt was made to measure neutral documented that when rabbits, rats, and hamsters are maintained on certain types of semi-purified formulations their sterol excretion in the present studies, it follows from the preceding data for cholesterol synthesis, dietary intake and rates of bile acid excretion are invariably far lower than when they are fed cereal-based (chow) diets. 19,38,39,41,[51][52][53][55][56][57][58][59][60][61][62][63] While bile acid excretion that adult male hamsters fed a plain diet should excrete a total of about 2.6 mg of cholesterol and other the reasons for this are unclear, it was decided that only the latter type of diet would be used in the present studies.…”

Section: Discussionmentioning

confidence: 99%

“…19, 41 Fecal bile acid content was measured enzymatically as were generated by daily measurements over three consecutive 24-previously described, 19 except that [carboxyl-…”

Section: Methodsmentioning

confidence: 99%

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Regulation of fecal bile acid excretion in male golden Syrian hamsters fed a cereal-based diet with and without added cholesterol

Turley

Spady

1997

Hepatology

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particular pharmacological agent or dietary treatment has The objective of these studies was to investigate the any effect on bile acid metabolism can be resolved by the comparative physiology and regulation of bile acid memeasurement of a number of related parameters. While the tabolism in the male Golden Syrian hamster by measurdetermination of bile acid pool size and composition provides ing the rate of fecal bile acid excretion and bile acid pool useful information, it is preferable to obtain a measure of the size in animals fed a cereal-based diet either alone, or overall rate at which cholesterol is degraded to bile acids. with added cholesterol or cholestyramine. In groupThis is now most widely performed by determining the activhoused hamsters fed only the plain diet fecal bile acid ity of cholesterol 7a-hydroxylase, the first and rate-limiting excretion in animals at 6, 10, and 15 weeks of age averstep in the biosynthetic pathway, or the level of messenger aged 11.0, 8.0, and 6.9 mmol/d per 100 g body weight (bw), RNA for this enzyme in the liver. [7][8][9][10][11] However, this approach respectively. Pool size, measured by subtracting from the total amount of bile acid washed out over 12 hours can be difficult because the basal level of activity of this enof biliary diversion the amount of bile acid excreted in zyme is very low in some species, and shows significant diurthe stools over the same period, equalled 17.8 mmol/100 nal variation in others.12,13 Furthermore, such measurements g bw in 15-week-old hamsters fed the plain diet. Hence, give only relative values and cannot be used to calculate the under basal conditions, these animals turned over about true amount of bile acid that is synthesized. The alternative 38% of their bile acid pool daily. In hamsters fed a diet approach is to determine the rate of fecal bile acid excretion, with 3% cholestyramine for 18 days, fecal bile acid excre-which under steady-state conditions provides a measure of tion averaged 20.6 mmol/d per 100 g bw, and the pool size the absolute rate of bile acid synthesis. contracted to 5.8 mmol/100 g bw. In matching animals fedAlthough there is an extensive literature on the comparaa diet containing 0.12% cholesterol for 30 days, hepatic tive physiology of several aspects of cholesterol and lipoprocholesterol levels increased from 1.9 { 0.1 to 12.6 { 0.7 tein metabolism in a number of different animal models, mg/g, fecal bile acid excretion increased marginally from there are few quantitative data relating to the basal rates of 5.8 to 8.0 mmol/day per 100 g bw, while pool size was bile acid synthesis in these particular species.14 Among these unchanged (16.6 mmol/100 g bw). When the cholesterol is the male Golden Syrian hamster which has proved to be an content of the diet was raised to 1.0%, hepatic cholesterol attractive model for investigating the mechanisms of action of levels reached 66.5 { 2.6 mg/g, but bile acid excretion many different classes of hypolipidemic agents [15][16][17][18][19][20][21] and also remained at 8 m...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Regulation of fecal bile acid excretion in male golden Syrian hamsters fed a cereal-based diet with and without added cholesterol

Turley

Spady

1997

Hepatology

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“…Cholestyramine in this dose range clearly increases fecal bile acid excretion (46); however, depletion of the enterohepatic pool ofbile acids is largely prevented by derepression ofhepatic 7a-hydroxylase so that cholesterol absorption efficiency is not affected (24,47). Similarly, dietary psyllium has little or no effect on the fecal excretion ofneutral steroids or on cholesterol absorption efficiency (8,20,24,47).…”

Section: Discussionmentioning

confidence: 99%

Regulation of hepatic 7 alpha-hydroxylase expression by dietary psyllium in the hamster.

Horton¹,

Cuthbert²,

Spady³

1994

J. Clin. Invest.

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Soluble fiber consistently lowers plasma total and low density lipoprotein (LDL)-cholesterol concentrations in humans and various animal models including the hamster; however, the mechanism of this effect remains incompletely defined. We performed studies to determine the activity of dietary psyllium on hepatic 7a-hydroxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and LDL receptor expression in the hamster. In animals fed a cholesterol-free semisynthetic diet containing 7.5% cellulose (avicel) as a fiber source, substitution of psyllium for avicel increased hepatic 7a-hydroxylase activity and mRNA levels by 34-fold. Comparable effects on 7a-hydroxylase expression were observed with 1% cholestyramine. Psyllium also increased hepatic 7a-hydroxylase activity and mRNA in animals fed a diet enriched with cholesterol and triglyceride. Activation of 7a-hydroxylase was associated with an increase in hepatic cholesterol synthesis that was apparently not fully compensatory since the cholesterol content of the liver declined. Although dietary psyllium did not increase hepatic LDL receptor expression in animals fed the cholesterol-free, very-low-fat diet, it did increase (or at least restore) receptor expression that had been downregulated by dietary cholesterol and triglyceride. Thus, 7.5% dietary psyllium produced effects on hepatic 7a-hydroxylase and LDL metabolism that were similar to those of 1% cholestyramine. Induction of hepatic 7a-hydroxylase activity by dietary psyllium may account, in large part, for the hypocholesterolemic effect of this soluble fiber. (J.

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“…Bile acid sequestrants such as cholestyramine bind bile acids in the intestinal lumen, thereby preventing their reabsorption. Loss of bile acids from the enterohepatic circulation results in derepression of 7a-hydroxylase expression (6)(7)(8)(9)(10) and an increase in the rate of bile acid synthesis (9,11). The liver compensates for the accelerated loss of cholesterol by increasing the rate of de novo cholesterol synthesis and, if this is inadequate, by increasing the receptordependent uptake of LDL from plasma (10), thereby lowering circulating LDL levels.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated transfer of a gene encoding cholesterol 7 alpha-hydroxylase into hamsters increases hepatic enzyme activity and reduces plasma total and low density lipoprotein cholesterol.

Spady¹,

Cuthbert²,

Willard³

et al. 1995

J. Clin. Invest.

109

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Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment

Cited by 111 publications

References 14 publications

Regulation of fecal bile acid excretion in male golden Syrian hamsters fed a cereal-based diet with and without added cholesterol

Regulation of fecal bile acid excretion in male golden Syrian hamsters fed a cereal-based diet with and without added cholesterol

Regulation of hepatic 7 alpha-hydroxylase expression by dietary psyllium in the hamster.

Adenovirus-mediated transfer of a gene encoding cholesterol 7 alpha-hydroxylase into hamsters increases hepatic enzyme activity and reduces plasma total and low density lipoprotein cholesterol.

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