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1.
Bengt E. Gustafsson Bo Angelin Ingemar Björkhem Kurt Einarsson Jan-Åke Gustafsson 《Lipids》1981,16(4):228-233
The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid
synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with
0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis
of cholesterol and bile acids. When the sampling period was finished, the rats were killed and the liver microsomal fractions
isolated. The activities of HMG CoA reductase and cholesterol 7α-hydroxylase were determined, the 7α-hydroxylase by a mass
fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and β-muricholic acid. During
treatment with chenodeoxycholic acid, 60–70% of this bile acid was converted into α- and β-muricholic acid, indicating a high
activity of the 6β-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7α-hydroxylase activity
was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase was unchanged.
The fecal excretion of cholesterol increased 2–3 times. An accumulation of cholesterol was seen in the rats treated with 1%
chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids. 相似文献
2.
The effect of chitosan feeding (for 21 days) on intestinal bile acids was studied in male rats. Serum cholesterol levels in
rats fed a commercial diet low in cholesterol were decreased by chitosan supplementation. Chitosan inhibited the transformation
of cholesterol to coprostanol without causing a qualitative change in fecal excretion of these neutral sterols. Increased
fiber consumption did not increase fecal excretion of bile acids, but caused a marked change in fecal bile acid composition.
Litcholic acid increased sigificantly, deoxycholic acid increased to a leasser extent, whereas hyodeoxycholic acid and the
6β-isomer and 5-epimeric 3α-hydroxy-6-keto-cholanoic acid(s) decreased. The pH in the cecum and colon became elevated by chitosan
feeding which affected the conversion of primary bile acids to secondary bile acids in the large intestine. In the cecum,
chitosan feeding increased the concentration of α-,β-, and ω-muricholic acids, and lithocholic acid. However, the levels of
hyodeoxycholic acid and its 6β-isomer, of monohydroxy-monoketo-cholanoic acids, and of 3α, 6ξ, 7ξ-trihydroxy-cholanoic acid
decreased. The data suggest that chitosan feeding affects the metabolism of intestinal bile acids in rats. 相似文献
3.
Klyohisa Uchida Takashi Aklyoshi Hirotsune Igimi Haruto Takase Yasuharu Nomura Shouichi Ishihara 《Lipids》1991,26(7):526-530
The preventive effect of 3α,7β,12α-trihydroxy-5β-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation
of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five
weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic
acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma
and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and
phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not
by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid
and β-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic
acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences
were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile
acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the
lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic
acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption.
Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora
in mice. 相似文献
4.
Yasuharu Imai Sumio Kawata Masami Inada Shio Miyoshi Yuzo Minami Yuji Matsuzawa Kiyohisa Uchida Seiichiro Tarui 《Lipids》1987,22(7):513-516
Effects of cholestyramine on biliary secretion of cholesterol, phospholipids and bile acids and fecal excretion of sterols
and bile acids were examined in Wistar male rats. Six rats were fed a basal diet, and the other six were fed a basal diet
supplemented with 5% cholestyramine for eight days. Bile flow and biliary secretion of bile acids and phospholipids (per hour
per rat) decreased with cholestyramine treatment, while biliary cholesterol secretion (per hour per rat) remained unchanged.
In the biliary bile acid composition, a marked increase of chenodeoxycholic acid with a concomitant decrease of β-muricholic
acid was observed in cholestyramine-treated rats. Fecal excretion of total sterols and bile acids increased about three-and
four-fold, respectively, after cholestyramine treatment. The increase of fecal bile acids derived from cholic acid was more
predominant than that derived from chenodeoxylcholic acid, resulting in an increase of the cholic acid group/chenodeoxycholic
acid group ratio. 相似文献
5.
Shigeru Hashimoto Hirotsune Igimi Kiyohisa Uchida Takashi Satoh Yoshimi Benno Nozomu Takeuchi 《Lipids》1996,31(6):601-609
Wistar male rats were treated for six days with broad spectrum β-lactam antibiotics, latamoxef, and cefotaxime. On the seventh
day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary
bile acids such as β-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary
bile acids, cholic, β-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol,
also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats,
whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned
to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks. 相似文献
6.
Takayuki Kayahara Toshihide Tamura Yoshiki Amuro Kazuya Higashino Hirotsune Igimi Kiyoshisa Uchida 《Lipids》1994,29(4):289-296
Bile acids were analyzed in the bile, small and large intestines, and feces of germ-free rats after a single inoculation with
one of six intestinal bacteria that had been originally isolated from human feces.Bacteroides vulgatus andBifidobacterium longum preferentially deconjugated tauro-β-muricholic acid and taurocholic acid, respectively.Clostridium ramosum, Peptostreptococcus productus andLactobacillus gasseri deconjugated both bile acids, butEscherichia coli did not deconjugate either one. Rats inoculated with bacteria that deconjugated tauro-β-muricholic acid produced Δ22-β-Muricholic acid in the feces. In contrast, Δ22-cholic acid could not be detected in rats inoculated with bacteria that deconjugated taurocholic acid. 相似文献
7.
Marie-Laure Favier Pierre-Etienne Bost Christian Demigné Christian Rémésy 《Lipids》1998,33(8):765-771
A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included
in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the
present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas
cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar
to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas
GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted
toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver
3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest
that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing
cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied
by reduction of bile acid concentration in the large intestine. 相似文献
8.
Significant correlations have been reported by epidemiologists between the mortality from colorectal cancer in various populations
and the consumption of meat or lipids by these populations. These have directed considerable attention to possible relationships
between diet and the occurrence of this neoplasm. We have carried out studies of the composition of bile from rats as influenced
by diets of varying lipid content. Two cannulas were surgically implanted to form an externalized bile duct through which
bile was drained from the common duct and returned to the duodenum. Small aliquots were analyzed for total bile acids by enzymatic
assay and for individual bile acids by high-pressure liquid chromatography, gas chromatography and gas chromatography-mass
spectrometry. Animals consuming diets highest in lipid content provided bile with the greatest amounts of bile acids. The
primary bile acids, taurocholic, taurochenodeoxycholic, and tauro α- and β-muricholic acids made up more than 99% of the 3α-hydroxy
bile acids and were found in approximate molar ratio of 2∶1∶1. Either complete drainage of bile without return to the duodenum,
or biliary tract obstruction had pronounced influence on the rate of secretion of bile and its composition. 相似文献
9.
Uchida K Satoh T Narushima S Itoh K Takase H Kuruma K Nakao H Yamaga N Yamada K 《Lipids》1999,34(3):269-273
The effects on bile acid and sterol transformation of clostridia (fusiform bacteria), the dominant intestinal bacteria in
rodents (ca. 1010 counts per g wet feces) were examined in Wistar rats. After inoculation of clostridia into germ-free rats and into rats previously
inoculated solely with Escherichia coli, most of the endogenous bile acids were deconjugated, and cholic acid and chenodeoxycholic acid were 7α-dehydroxylated to
deoxycholic acid and lithocholic acid, respectively. Tauro-β-muricholic acid, another major bile acid in rats, was deconjugated,
but only part of it (ca. 30%) was transformed into hyodeoxycholic acid. Cholesterol and sitosterol were also reduced to coprostanol and sitostanol,
respectively. Escherichia coli transformed neither bile acids nor sterols. These data suggest that clostridia play an imporant role in the formation of
secondary bile acids and coprostanol in rats. 相似文献
10.
Cholesterol synthesis and degradation in normal rats fed a cholesterol-free diet with excess cystine
Feeding a diet with excess cystine to rats resulted in hypercholesterolemia. To understand the mechanism of the hypercholesterolemia’
cholesterol synthesis and degradation’ bile acid content of bile’ and fecal steroids were determined. The in vivo incorporation of tritiated water into hepatic cholesterol’ and activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase
in rats fed a high-cystine diet were significantly higher than those in rats fed a control diet. The activity of hepatic cholesterol
7α-hydroxylase was similar between two groups. Little effect of cystine supplementation was found on fecal sterol excretion
although there were some changes in biliary excretion of cholic acid derivatives. These results indicate that hypercholesterolemia
caused by feeding of a high-cystine diet may be due to the stimulation of hepatic cholesterol synthesis. 相似文献
11.
The effect of 4-0-methylascochlorin (MAC), an experimental hypocholesterolemic agent, on cholesterol metabolism was investigated
in rats in two separate experiments. The administration of MAC for 2 and 6 consecutive weeks at daily doses of 100–135 mg/kg
resulted in reduction in serum cholesterol levels of 16% after 2 weeks of treatment in the first experiment, and 13% after
6 weeks in the second experiment in comparison to the corresponding controls. MAC administered at a daily dose of 100 mg/kg
for 2 weeks showed a significant increase in the biliary excretion of bile acids and cholesterol in bile-duct cannulated rats
with or without the administration of taurocholate. In the second experiment, MAC treatment for 6 weeks produced a marked
increase in the fecal output of acidic sterols during a 2 to 6-week period. MAC treatment also further enhanced hepatic cholesterol
7α-hydroxylase in the rats. Therefore, it appears that the mechanism of serum cholesterol lowering due to MAC is related to
the enhancement of hepatic bile acid synthesis and the increase in biliary and fecal excretion of bile acids. 相似文献
12.
Naoyuki Matoba Syoji Kuroki Bertram I. Cohen Erwin H. Mosbach Charles K. McSherry 《Lipids》1988,23(5):465-468
The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster.
Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid,
7-methyl-chenodeoxy-cholic acid, 7β-methyl-24-nor-5β-cholestane-3α,7α,25-triol, cholic acid, 7-methyl-cholic acid, or 7β-methyl-24-nor-5β-cholestane-3α,7α,12α,25-tetrol.
Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and β-sitosterol.
Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption
(17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease),
but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total
fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In
addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid
resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies
of its gallstone-dissolving properties. 相似文献
13.
The influence of feeding cholesterol to rats during pregnancy and postpartum (from the 11th day of gestation to the third
day after delivery) on the serum and hepatic cholesterol levels and on the bile acid composition in the pool and in the liver
in relationship to the dams and their pups was examined. The hepatic content of cholesterol in both dam and offspring increased
during cholesterol feeding without any changes in serum cholesterol level. In the dams, mainly the esterified cholesterol
was increased; in the pups, mainly the free cholesterol was increased. Cholesterol feeding led to a pronounced increase in
the pool of β-muricholic acid and a relative decrease in the lithocholic acid concentration in pregnant rats. In fetal rats,
the chenodeoxycholic acid pool was increased by cholesterol intake. The lithocholic acid pool was larger in the postpartum
rats fed cholesterol than in the controls, while the concentration of α- and β-muricholic acids was decreased. The neonates
of cholesterol-fed dams had a larger pool of chenodeoxycholic acid but a smaller pool of β-muricholic acid. These results
suggest that the metabolism of cholesterol and of bile acids in dams and their offspring respond differently to cholesterol
intake. 相似文献
14.
Marie-Laure Favier Pierre-Etienne Bost Christine Guittard Christian Demigné Christian Rémésy 《Lipids》1997,32(9):953-959
The effects of partially hydrolyzed, nonviscous, guar gum (PHGG) on cholesterol metabolism and digestive balance have been
compared with those of native guar gum (GUAR) in rats adapted to 0.4% cholesterol diets. Both types of guar gum elicited acidic
fermentations in the large intestine, but only GUAR effectively lowered plasma cholesterol (P<0.001), chiefly in the triglyceride-rich lipoprotein fraction. The biliary bile acid excretion was significantly enhanced
in rats fed GUAR (P<0.05), as well as the intestinal and cecal bile acid pool (P<0.001). In rats fed GUAR and to a lesser extent in those fed PHGG, the fecal excretion of bile acids and neutral sterol was
higher than in controls (P<0.01). The digestive balance (cholesterol intake-steroid excretion) was positive in control rats (+47 μmol/d), whereas it
was negative in rats fed GUAR (−20 μmol/d), which could involve a higher rate of endogenous cholesterol synthesis. In rats
fed PHGG, the steroid balance remained slightly positive. Liver 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity
was very low (22 pmol/min/mg protein), owing to cholesterol supplementation, in control rats or in rats fed PHGG, whereas
it was markedly higher (+463%) in rats fed GUAR. In conclusion, even if PHGG does alter some parameters of the enterohepatic
cycle of cholesterol and bile acids, its effects are not sufficient to elicit a significant cholesterol-lowering effect. The
intestinal (ileal or cecal) reabsorption of bile acids was not reduced, but rather increased, by GUAR; nevertheless the intestinal
capacities of reabsorption were overwhelmed by the enlargement of the digestive pool of bile acids. In the present model,
induction of HMG-CoA reductase probably takes place in the presence of elevated portal bile acid concentrations. 相似文献
15.
Germfree (GF) mice were orally inoculated with human fecal suspension or various components of human fecal microbiota. Three
weeks after the inoculation, cecal bile acid composition of these mice was examined. More than 80% of total bile acids was
deconjugated in the cecal contents of ex-GF mice associated with human fecal dilutions of 10−2 or 10−6, or anaerobic growth from a dilution of 10−6. In these ex-GF mice, deoxycholic acid accounted for about 20% of total bile acids. In the cecal contents of ex-GF mice associated
only with clostridia, unconjugated bile acids made up less than 40% of total bile acids, about half of those in other ex-GF
groups. However, the percentage of deoxycholic acid in these mice was the same as that in the other groups. These results
indicate that dominant anaerobic bacterial combination is efficient for deconjugation of primary bile acids, and that clostridia
in the human feces may play an important role in 7α-dehydroxylation of unconjugated primary bile acids in the intestine. 相似文献
16.
Bertram I. Cohen Takahiro Mikami Nariman Ayyad Akira Ohshima R. Infante Erwin H. Mosbach 《Lipids》1995,30(9):855-861
The effects of β-muricholic acid and hyocholic acid on cholesterol cholelithiasis were examined in two animal models. The
following experiments were carried out: A) In a gallstone prevention study, prairie dogs were fed the lithogenic diet with
or without 0.1% β-muricholic or 0.1% hyocholic acid for eight weeks. B) In a second prevention study, hamsters were fed the
lithogenic diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid for six weeks. C) In a gallstone dissolution
study, hamsters were fed the lithogenic diet for six weeks to induce stones; stone dissolution was examined during administration
of a cholesterol-free purified diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid. In the prevention study
in prairie dogs (A), both bile acids failed to prevent stone formation, the cholesterol saturation index of bile was 0.89
in the lithogenic controls, remained unchanged with hyocholic acid and increased to 1.52 in the β-muricholic acid group. In
the prevention study in hamsters (B), β-muricholic acid completely inhibited the cholesterol cholelithiasis (0% stone incidence);
the cholesterol saturation index of bile was 1.78 (compared to lithogenic controls, 1.37). Hyocholic acid reduced stone incidence
to 16% with a cholesterol saturation index of 0.98. In the dissolution study in hamsters (C), preexisting cholesterol gallstones
were not dissolved by either hydrophilic bile acid after feeding these bile acids for an additional six weeks; at the end
of the experiment, the cholesterol saturation indices were below unity. These studies suggest that, in the hamster animal
model, hydrophilic bile acids may be useful for the prevention of gallstones but not dissolution of preestablished cholesterol
gallstones. 相似文献
17.
The study on the metabolism after oral administration of chenodeoxycholic acid-24-14C was performed by analysis of radioactivity that had appeared in bile and feces of male hamsters. The radioactive bile acids
were analyzed by thin layer chromatography and identified by the isotope dilution method. In the bile of the hamsters with
bile fistula, radioactivity was originated from unchanged chenodeoxycholic acid for the most part, and 7-ketolithocholic acid,
lithocholic acid, and β-muricholic acid for the remainder. In the feces lithocholic acid, dehydrolithocholic acid, isolithocholic
acid, and unchanged form were identified. After the multiple dosing of chenodeoxycholic acid-24-14C for 6 days, β-muricholic acid was also identified in the feces. 相似文献
18.
Deconjugation of bile acids by human intestinal bacteria implanted in germ-free rats 总被引:6,自引:0,他引:6
Fecal bile acids in germ-free rats were analyzed after inoculation withBacteroides vulgatus, Bifidobacterium longum, Escherichia coli orClostridium ramosum. B. vulgatus preferentially deconjugated tauro-β-muricholic acid andB. longum taurocholic acid.C. ramosum deconjugated both bile acids, butE. coli deconjugated neither. 7α-Dehydroxylation of bile acids was negligible even after 18 days of inoculation, but a small amount
of 7-oxo-bile acid, less than 5%, was formed. Fecal excretion of bile acids increased after inoculation withB. vulgatus, B. longum andC. ramosum, but not withE. coli. 相似文献
19.
The effect of cabbage extract on cholesterol metabolism was studied in Donryu rats subcutaneously implanted with an ascites
hepatoma cell line (AH109A). The hepatoma-bearing rats exhibited hypercholesterolemia induced by increasing cholesterogenesis
in the host liver and decreasing steroid excretion into feces. The cabbage extract intake or administration reduced serum
cholesterol level and enhanced fecal bile acid excretion and cholesterol 7α-hydroxylase activity, the rate-limiting enzyme
of bile acid biosynthesis, in the microsomal fraction of the liver. Furthermore, S-methyl-l-cysteine sulfoxide, a component of cabbage, could mimic the effect of cabbage extract when orally administered. These results
suggest that cabbage suppresses hypercholesterolemia responding to hepatoma growth by upregulating cholesterol catabolism
and that S-methyl-l-cysteine sulfoxide in cabbage is one of the factors suppressing hypercholesterolemia in the hepatoma-bearing rats. 相似文献
20.
The bile acid concentrations in the serum, liver, bile, intestines, and feces of 3- and 19-mon-old male and female Nagase
analbuminemic (NA) rats were compared with those in Sprague-Dawley (SD) rats. There was no significant difference in the bile
acid levels between NA and SD rats. However, increased biosynthesis and pool size of cholic acid (CD) derivatives and decreased
levels of chenodeoxycholic acid (CDCA) derivatives (increased CA/CDCA ratio) were detected in male NA rats as compared to
SD rats. The CA/CDCA ratio in female NA rats was not different from that in their SD rats in the biliary bile flow, bile acid
levels in the small and large intestines, fecal bile acid excretion, bile acid concentration in the portal and systemic circulation,
and in the pool size of bile acids. The blood lipid concentrations were significantly higher in the NA rats than in the SD
rats. The hepatic levels of lipids were not significantly different between the two rat strains. In conclusion, this study
showed that metabolism of bile acids in NA rats is not significantly affected, and that the hypercholesterolemia observed
in these strains is not related to abnormalities of bile acid metabolism. 相似文献