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1.
Bertram I. Cohen Erwin H. Mosbach Nariman Ayyad Shigeo Miki Charles K. McSherry 《Lipids》1992,27(7):526-532
We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones
in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol
cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein,
corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil,
corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or
illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence
of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones
entirely (groups 2–4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones
increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional
4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2%
palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of
its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as
inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model. 相似文献
2.
Cholesterol gallstones were produced in young male, golden Syrian hamsters, obtained from three different suppliers, by administering
a nutritionally adequate, semipurified diet for periods of either 5 or 10 weeks. The major components of the lithogenic diet
were casein, cornstarch, butterfat, corn oil and 0.3% cholesterol. The hamsters were obtained from Sesco, Harlan Sprague-Dawley
(Engle hamster) and Charles River (Lakeview hamster). There were profound differences among the three groups with respect
to gallstone formation and cholesterol metabolism: The highest incidence of gallstones occurred in Sesco hamsters, 44.4% and
63.6% after 5 and 10 weeks on the lithogenic diet, respectively. In the Engle hamster, after a 5-week feeding, cholesterol
crystals and gallstones were absent. When the feeding period was extended to 10 weeks, cholesterol gallstones were present
in 45.5% of the animals. In the Lakeview hamsters, neither gallstones nor cholesterol crystals were found in the gallbladder
after a 5-week period. After 10 weeks, cholesterol gallstones were found in only a single hamster. In all groups, the lithogenic
diet produced large increases of liver, serum and biliary cholesterol concentrations and increased liver weights. When the
animals were fed for 5 weeks, only the bile of Sesco hamsters became supersaturated. Supersaturated bile was induced in all
groups after a 10-week feeding of the lithogenic diet with cholesterol saturation ranging from 1.47 to 1.97. These data indicate
that it is possible to induce cholesterol gallstones in hamsters by means of a nutritionally adequate, semipurified diet of
moderate cholesterol content. The source of the animals appears to be an important variable, because there were significant
differences among the hamsters of differing origins, in cholesterol metabolism and rates of gallstone formation. 相似文献
3.
Bertram I. Cohen Takahiro Mikami Nariman Ayyad Yasuko Mikami Erwin H. Mosbach 《Lipids》1995,30(4):299-305
The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The
present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure
(vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington,
MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol;
(ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and
the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of
ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River
animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles
(28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume
vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for
six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion
of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight
identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the
biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%). Vesicles were not detected in
the bile of hamsters fed cholesterol-free diets, and none of these animals developed cholesterol gallstones. Safflower oil
diets inhibited stone formation even though the cholesterol saturation index was above unity. After six weeks, biliary cholesterol
transported in void volume vesicles was highest for Sasco hamsters (13.3%) as compared to Charles River animals (6.9%), but
total cholesterol transported in void volume vesicles plus small vesicles was similar in both groups (33.5% vs. 26.2%), respectively.
These results suggest that in both strains of hamsters dietary fat influences gallstone formation by modulating the vesicular/micellar
distribution of biliary cholesterol. Apparently, the presence of cholesterol/phospholipid vesicles in bile is associated with
cholesterol gallstone formation. 相似文献
4.
We examined the effect of diet on gallstone incidence and the composition of biliary phosphatidylcholines in methyltestosterone-treated
female hamsters. These hamsters were fed a nutritionally adequate purified lithogenic diet containing 2% corn oil, 4% butterfat,
0.3% cholesterol, and 0.05% methyltestosterone, resulting in a cholesterol gallstone incidence of 86%. This incidence was
lowered when mono-and polyunsaturated fats or fatty acids were added to the diet: 2.5% oleic acid resulted in total prevention
of cholesterol cholelithiasis, 2.5% linoleic acid, and 4% safflower oil (78% linoleic acid content) reduced gallstone incidence
to 26 and 8%, respectively. An additional 4% butterfat (29% oleic acid content) produced gallstones in 50% of the animals.
At the end of the 6-wk feeding period, the bile of all hamsters was supersaturated with cholesterol. The major biliary phosphatidylcholine
species in all groups were (sn-1-sn-2): 16:0–18:2, 16:0–18:1, 18:0–18:2, 16:0–20:4, and 18:2–18:2. The safflower oil-and linoleic acidfed hamsters exhibited
an enrichment of 16:0–18:2 (16–18%); added butterfat or oleic acid increased the proportion of 16:0–18:1 (9 and 25%, respectively).
We conclude that the phosphatidylcholine molecular species in female hamster bile can be altered by dietary fats/fatty acids
and that mono-and polyunsaturated fatty acids play a role in suppressing the induced cholelithiasis. 相似文献
5.
In the prairie dog model of cholesterol cholelithiasis, a high incidence of gallstones is achieved by feeding a semipurified
lithogenic diet containing 0.4% cholesterol for 2 mo. On occasion, we noted a decrease in the percentage of animals with gallstones
from 90–100% to 50–55%. To explain this phenomenon, we studied the effect of dietary history on gallstone formation. After
weaning, animals were fed either rodent chow or alfalfa plus corn (mo 0–3) followed by a cross-over experiment at mo 4–6.
Gallstone formation then was studied by feeding the lithogenic diet from mo 7 to 8. At sacrifice, the incidences of gallstones,
biliary lipids and tissue cholesterol levels were correlated with dietary history. The incidence of gallstones was 100% only
in animals fed the alfalfa-corn diet from weaning to 3 mo. In addition, the feeding of the alfalfa-corn diet at mo 4–6 increased
gallstone incidence from 65% to 86%. The lithogenic index of all groups was highest when the animals received only alfalfa-corn
prior to the lithogenic stimulus. The activity of hepatic HMG-CoA reductase was elevated in animals fed alfalfa-corn from
weaning to 8 mo, suggesting that this diet stimulates hepatic cholesterol synthesis, leading to increased biliary cholesterol
secretion. It is concluded that previous nutritional conditioning affects the incidence of gallstones. The prairie dog is
a useful model of cholesterol cholelithiasis, but the dietary history of the animals plays an important role in lithogenesis. 相似文献
6.
Takahiro Mikami Bertram I. Cohen Yasuko Mikami Nariman Ayyad Erwin H. Mosbach 《Lipids》1994,29(8):529-534
The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco
Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a
semipurified diet with 0.3% cholesterol and 1.2% plamitic acid (group 2, males; group 5, females); and a semipirified diet
with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found
only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group
2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration
chromatography, using the method of Pattinson [Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991)J. Lipid Res. 32, 205–214]. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in
the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in
group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30–45) and contained 15% of biliary cholesterol
in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt
micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48
in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3). In contrast, the
bile of the female hasmters contained few vesicles (3% small vesciles in group 5) and the cholesterol/phospholipid ratio of
these vesicles was lower (0.94). Hamsters fed cholesterol-free diets (groups 1 and 4) had no biliary cholesterol/phospholipid
vesilces; and cholesterol was present in micelles. The results suggest that both the gender and the diet of the hamsters affected
the distribution of biliary cholesterol between vesicles and micelles. The development of cholelithiasis in this animal model
appears to depend on the rapid nucleation of cholesterol-rich phospholipid vesicles in bile. 相似文献
7.
Bertram I. Cohen Erwin H. Mosbach Charles K. McSherry Beverly Rzigalinski Syoji Kuroki 《Lipids》1986,21(9):575-579
Gallstone formation and dissolution were studied in a prairie dog model of cholesterol (CH) cholelithiasis. Gallstones were
induced in 49 prairie dogs by feeding 1.2% CH in a nutritionally adequate semisynthetic diet for 6 wk (period 1). At 6 wk,
gallstones had developed in all animals examined. The diets were modified by reducing the amounts of CH to 0.4, 0.2, 0.1 and
0.0% (diets 1–4); hyodeoxycholic acid (HDA; 30 mg/kg/day) was added to these diets (diets 5–8). All animals were fed the modified
experimental diets for an additional 8 wk (period 2). At week 14, spontaneous gallstone dissolution had not occurred, even
in the groups given no added dietary CH during period 2 (group 4). Addition of HDA to the diet tended to reduce the incidence
of biliary CH crystals and the size and number of CH gallstones. Biliary CH remained elevated and the lithogenic indices in
all groups were found to be greater than 1.0 at the end of the experiment. Liver and plasma CH levels tended to be lower in
the groups fed HDA. In these groups, HDA and 6βHDA became the major biliary bile acids. This study demonstrates that HDA achieved
partial dissolution of gallstones in bile supersaturated with CH. 相似文献
8.
To test the possibility that dietary palmitic acid (16∶0) may be lithogenic, different fats were blended to exchange 18∶1
in olive oil with either 16∶0 in palm stearin, 12∶0+14∶0 in coconut oil, or 14∶0+16∶0 in butterfat. Dietary 18∶2 was held
constant at 1.2% energy (en) (with extra safflower oil as needed) in these four purified diets containing low fat (11% of
total energy) and 0.4% cholesterol. A fifth, high-fat diet provided 40% of the total energy as the 16∶0-rich blend. All hamsters
fed the low-fat, 16∶0-rich blend for six weeks developed cholesterol gallstones (8/8). Although the gallstone incidence was
lower for the 12∶0+14∶0-rich diet (5/8), the severity of stone formation in affected hamsters was equal to that in the low-fat,
16∶0-rich group. Mucin accumulation in gallbladder bile was often associated with cholesterol gallstones in diets containing
16∶0, but was minimal in 18∶1-rich and 12∶0+14∶0-rich groups. Neither the lithogenic index (all>1.0), plasma lipids, nor liver
cholesterol was a selective predictor of stone formation. The high-fat, 16∶0-rich diet actually decreased cholesterol stone
incidence (3/8) and severity, but yielded a high incidence of pigment stones (5/8). Thus, saturated fat and 16∶0per se were not responsible for the exaggerated lithogenesis. Because the antilithogenic 18∶1-rich diet also normalized the 18∶2
intake (1.2% en) relative to previous butter diets (0.3% en), the potential importance of essential fatty acids (EFA) deficiency
in the model was tested in a second study by feeding graded amounts of 18∶2 (0.3, 0.6, 0.9, and 1.2% en) as safflower oil
in four low-fat, butter-rich diets (11% en as fat) without alleviating gallstone incidence or severity. These studies indicate
that substitution of 18∶1 for saturated fatty acids in low-fat diets reduces gallstone formation without affecting the lithogenic
index. Furthermore, intake of 18∶2 at or below the EFA requirement does not appear to be a major factor in this model. 相似文献
9.
Bertram I. Cohen Nariman Ayyad Takahiro Mikami Yasuko Mikami Erwin H. Mosbach 《Lipids》1994,29(7):503-508
Sterol balance studies, using both isotopic and chromatographic techniques, were carried out in hamsters fed semipurified
diets to detect changes in sterol metabolism during the early period of the lithogenic stimulus. The balance studies examined
animals in the first two weeks on the experimental lithogenic diets. The variables were as follows: dose of cholesterol (group
1, 0.05% vs. group 2, 0.2%); dietary fat (fatty acid) (group 2, butterfat vs. group 4, palmitic acid); source of hamster [group
2, Sasco (Omaha, NE) vs. group 3, Charles River (Wilmington, MA)]; average weight of animals (group 4, 60 g vs. group 5, 119
g). Animals in groups 1, 2, 3 and 5 maintained almost constant weight throughout the two-week balance study. Liver and plasma
cholesterol levels increased in groups 2–5 with increasing dose of dietary cholesterol. The highest levels were found in group
4 (liver cholesterol, 32.7 mg/g; plasma cholesterol, 367 mg/dL). Sterol balance measurements showed that bile acid synthesis
remained low (range 0.55–1.01 mg/d) for all groups regardless of the intake of dietary cholesterol (range, 3.27–20.90 mg/d).
The dietary cholesterol absorbed from the intestine (range, 2.91–18.91 mg/d) was stored in the liver; this storage was reflected
in the negative values for cholesterol balance for all groups (range, −0.70 to −14.97 mg/d). These studies did not reveal
any correlations between parameters of sterol balance and cholelithiasis. 相似文献
10.
Bertram I. Cohen Naoyuki Matoba Erwin H. Mosbach Richard J. Stenger Charles K. McSherry 《Lipids》1989,24(6):482-487
Dietary cholic acid (0.1%) and/or calcium (2.6% as calcium carbonate) were added to a semipurified diet containing cholesterol
and ethynyl estradiol to determine whether the incidence of pigment and/or cholesterol gallstones would be changed. Male golden
Syrian hamsters were fed the experimental diets for 96 days (Group 1, control; Group 3, cholic acid plus calcium) or only
an average of 60 days (Group 2, 0.1% cholic acid). Animals in Group 2 became ill (weight loss, low food intake, diarrhea)
possibly due to cholic acid (or deoxycholic acid) toxicity. Cholesterol gallstones and crystals were absent in all experimental
groups. The incidence of pigment gallstones was: control, Group 1, 12/16; 0.1% cholic acid, Group 2, 3/13; and 0.1% cholic
acid plus calcium, Group 3, 11/22. Cholic acid with or without calcium produced an elevation of both liver and plasma cholesterol:
Group 2, 80.1 mg/g and 501 mg/dl; Group 3, 103.7 mg/g and 475 mg/dl vs Group 1, 65 mg/g and 209 mg/dl, respectively. The lithogenic
indices of the bile were lower in Groups 2 and 3 compared to Group 1, controls, 0.45 and 0.58 vs 1.16, respectively. The extent
of the portal tract pathology could not be correlated with the presence or absence of pigment gallstones or with the levels
of lithocholic acid in the hamster bile. In summary, when semipurified diets were supplemented with ethynyl estradiol and
cholic acid, with and without calcium supplementation, no cholesterol gallstones formed and the incidence of pigment gallstones
was not altered. 相似文献
11.
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
12.
Dietary fat alters biliary lipid secretion in the hamster 总被引:1,自引:0,他引:1
Dietary fat has been found to alter the incidence of cholesterol gallstones in hamsters: butterfat intensifies while safflower
oil reduces lithiasis. We now report how dietary fat affects bile flow and biliary lipid secretion in this model. Male hamsters
were fed one of three experimental diets: a control diet (containing 0.3% cholesterol); control diet +4.0% butterfat; or control
diet +4.0% safflower oil. After three weeks, bile samples were collected via an external biliary fistula. The endogenous bile
acid pool was depleted for 120 min followed by increasing rates of taurocholate infusion for 160 min. Basal secretion of biliary
lipids was measured during the bile acid depletion period. Basal bile flow and bile acid output were not significantly different
in the three groups. Dietary butterfat increased basal cholesterol output compared to the control diet (0.037 vs. 0.025 μmol/min·kg,
respectively); safflower oil did not change cholesterol output (0.027 μmol/min·kg). Hamsters fed butterfat or safflower oil
secreted more phospholipid (0.171 and 0.178 μmol/min·kg, respectively) than controls (0.131 μmol/min·kg). The cholesterol/phospholipid
output ratio of the butterfat group was higher than the safflower oil group (0.220 vs. 0.153, respectively). Effects of dietary
fat on several relationships between bile flow and biliary lipid secretion were analyzed by linear regression using the data
for the entire bile collection period (bile acid depletion and taurocholate infusion). Butterfat and safflower oil did not
change either bile acid dependent or bile acid independent bile flow. Hamsters fed butterfat had a higher linkage coefficient
(slope) of cholesterol vs. bile acid output than the safflower oil group (0.023 vs. 0.009, respectively). The linkage coefficient
of phospholipid vs. bile acid output of the butterfat group was higher than the controls (0.278 vs. 0.185, respectively).
In summary, butterfat induced a high cholesterol and phospholipid secretion with a high cholesterol/phospholipid output ratio;
safflower oil induced a high phospholipid secretion with a low cholesterol/phospholipid output ratio. Butterfat and safflower
oil have different effects on biliary lipid secretion. These differences in biliary lipid secretion may explain, in part,
how butterfat and safflower oil differ in affecting gallstone formation in hamsters. 相似文献
13.
Nariman Ayyad Bertram I. Cohen Erwin H. Mosbach Shigeo Miki Takahiro Mikami Yasuko Mikami Richard J. Stenger 《Lipids》1993,28(11):981-986
In the present study, we examined the effect of the following factors on a hamster model of cholesterol cholelithiasis: (i)
the source of the golden Syrian hamsters (Sasco, Omaha, NE or Charles River, Wilmington, MA), (ii) the sex of the experimental
animals and (iii) their age (4 wkvs. 8 wk of age). All hamsters were fed a semipurified diet which contained cholesterol (0.3%) and palmitic acid (1.2%). No cholesterol
gallstones formed in any of the female hamsters regardless of age or source. The 4-week-old male hamsters from Sasco had the
greatest incidence of gallstones (93%). The 8-week-old male hamsters tended to have a lower incidence of cholesterol gallstones
than the younger ones, regardless of the commercial supplier (67vs. 93% for Sasco and 27vs. 40% for Charles River). Female hamsters has higher liver and serum cholesterol levels than the male hamsters; Charles River
hamsters had lower serum cholesterol concentrations than the Sasco animals. Total biliary lipid concentrations were highest
in Sasco male hamsters, but biliary cholesterol (mol%) was lower in the males than in the females (4.2–4.5%vs. 6.1–7.1%) regardless of age. The cholesterol saturation indices were higher in the Sasco females than the corresponding males;
these values were lower in the Sasco hamsters than the Charles River animals, regardless of age or sex. The male Sasco hamsters
had a higher total biliary bile acid concentration (98.9 mg/mL) than the Sasco females (58.9 mg/mL) and the Charles River
animals (24.6% mg/mL for males and 38.2 mg/mL for females). The percentage of chenodeoxycholic acid in bile was significantly
lower, and the percentage of cholic acid was higher in all females as compared to males. We conclude that there is a sex,
age and “strain” difference in cholesterol cholelithiasis in hamsters; it is important to consider these factors when working
with the hamster model of gallstone disease. All female hamsters were markedly resistant to the induction of cholesterol gallstone
disease. 相似文献
14.
Male Syrian hamsters (60–70 g) were fed purified diets containing 5% fat (American Fat Blend) and 15% fiber with or without
0.3% cholesterol (0.86 mg/kcal), for 12 weeks. Hamsters fed the cholesterol-supplemented challenge diet revealed a major increase
in plasma triglyceride between 9 and 12 weeks, whereas plasma cholesterol (which reflected body weight dynamics) increased
three-fold up to nine weeks and plateaued (342±22vs. 122±5 mg/dL). The greatest increases in cholesterol occurred in the very low density lipoprotein (VLDL) and high density
lipoprotein (HDL2) fractions. Gallstone incidence was similar (69%vs. 78%) for cholesterol-supplementedvs. control hamsters, but the type of stones differed. Of the cholesterol-supplemented hamsters with gallstones, 45% had cholesterol
stones and 55% had pigment stones. Only pigment stones were seen in control hamsters. Hamsters with cholesterol stones were
25% heavier and transported most cholesterol in VLDL (33±5%), approximately double that in VLDL of cholesterol-supplemented
hamsters with no stones (19±3%) or cholesterol-supplemented hamsters with pigment stones (21±3%). Hamsters with pigment stones
or no stones (regardless of diet fed) transported the majority of their cholesterol in HDL2 (44%), whereas this figure was only 27% in hamsters that developed cholesterol stones. Thus pigment stones develop routinely
in hamsters fed casein-based purified diets. Adding dietary cholesterol resulted in cholesterol gallstones only in those hamsters
that gained the most weight and whose terminal VLDL/HDL cholesterol ratio exceeded 1.0, not unlike the lipoprotein profile
of obese humans who develop cholesterol gallstones.
Presented in part at the Xth International Symposium on Drugs Affecting Lipid Metabolism, November 8–11, 1989, Houston, TX. 相似文献
15.
The effect of chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid on gallstone dissolution was studied in
the prairie dog. Cholesterol gallstones were found in all animals after feeding a semipurified diet plus 1.2% cholesterol
for six wk. Gallstone regression was examined by feeding a chow diet containing the bile acids (chenodeoxycholic acid, ursodeoxycholic
acid or hyodeoxycholic acid) alone (30 mg/kg/day) or in combination (chenodeoxycholic acid plus ursodeoxycholic acid) for
an additional six wk. Chenodeoxycholic acid was effective in dissolving established cholesterol gallstones (two out of 16
animals still had stones) and cholesterol crystals (six out of 16 animals had crystals); the hydrophilic bile acids, ursodeoxycholic
acid and hyodeoxycholic acid, were ineffective in the six-wk regression study. The lithogenic indices averaged 1.09 at the
end of the induction period: all biles became unsaturated with respect to cholesterol after the six-wk regression period (group
1, 0.82; group 2, 0.66; group 3, 0.81; group 4,0.84; group 5, 0.66). Cholesterol levels in liver, plasma and bile were elevated
after the six-wk induction phase (4.59 mg/g, 610 mg/dl and 0.36 mg/ml, respectively) but returned to near normal levels after
the six-wk regression period. Biliary bile acids contained increased levels of the dietary bile acid administered to each
group. This experiment shows that relatively hydrophobic bile acids may be more effective than hydrophilic bile acids for
gallstone dissolution during the period studied. 相似文献
16.
This study examined the effect of castration and dietary hormonal supplementation on cholesterol cholelithiasis in male hamsters.
Animals fed a standard lithogenic diet developed cholesterol gallstones (17%) after 6 wk, while castrated hamsters did not
form any stones. Addition of a synthetic androgen, methyltestosterone, to the lithogenic diet induced cholelithiasis in castrated
animals (50%). The biles of normal and castrated-hormone supplemented hamsters had cholesterol saturation indices of 1.0 and
1.1, respectively, while the bile of the castrated animals remained unsaturated (0.6). The ratio of cholic acid/chenodeoxycholic
acid in bile increased after castration, but returned to normal levels following hormonal supplementation. Biliary cholesterol
carriers were separated by ultracentrifugation. Animals in the stone-forming groups (normal and castrated-hormone treated)
had a significant proportion of their biliary cholesterol in vesicles (44 and 46%, respectively); castrated hamsters had less
cholesterol in vesicle form (9%). The molar ratio of cholesterol/phospholipid in vesicles was reduced after castration (0.93
vs. 0.42) and increased by hormonal supplementation (1.89). In conclusion, when compared to normal male hamsters fed a standard
lithogenic diet, castration reduced the cholesterol saturation of bile, lowered the vesicular/micellar ratio in bile, and
inhibited cholesterol cholelithiasis. Dietary androgen supplementation increased the lithogenicity of bile, resulting in stone
formation in castrated animals. 相似文献
17.
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
18.
Rabbits were fed diets including cholesterol and 10% butterfat to determine whether polyunsaturated butter (9% 18∶2) would
be less atherogenic than normal saturated butter (3% 18∶2) when fed for 12 weeks. The cholesterol diets alone, 0.5% or 2%,
produced aortic plaque development, and plasma cholesterol increased 20 times, lipids increased 10 times, and vitamin E increased
5 times. The inclusion of both fat and cholesterol in the diet produced a synergistic effect, doubling these values to 40
times for cholesterol, 20 times for lipids, and 10 times for vitamin E. The higher circulating levels of cholesterol caused
increased tissue levels of cholesterol. With 2% cholesterol and fat, liver and aorta cholesterol increased 10 times, heart
4 times, and muscle cholesterol 2 times. The lower 0.5% dietary cholesterol load was successful in limiting the amount of
tissue cholesterol increase. Liver, aorta, heart, and muscle levels of cholesterol were only about half the concentration
attained when 2% cholesterol was fed. It was concluded that there were no differences in plasma or tissue cholesterol, vitamin
E, or atherosclerosis attributable to the polyunsaturated nature of the diet. The 10% butterfat diets alone, whether saturated
or unsaturated, did not induce aortic plaques and did not increase blood or tissue cholesterol, lipids, or vitamin E. Our
results suggest that the lipid mobilizing effect is mediated by cholesterol, probably by conversion to bile acids and a stimulation
in intestinal absorption. 相似文献
19.
Robert A. Gibson Mark A. Neumann Sharon L. Burnard Josephine A. Rinaldi Glen S. Patten Edward J. McMurchie 《Lipids》1992,27(3):169-176
Adult male marmoset monkeys were fed eicosapentaenoic acid (20∶5n−3) as the ethyl ester in diets containing either 32% (reference
diet, no added cholesterol) or 7% (atherogenic diet with 0.2% added cholesterol) linoleic acid (18∶2n−6) for 30 wk. No changes
were seen in the level of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) but minor changes were observed in both
the sphingomyelin (SPM) and phosphatidylinositol plus phosphatidylserine (PI+PS) fractions of erythrocyte lipids. The extent
of total n−3 fatty acid incorporation into membrane lipids was higher in atherogenic diets (polyunsaturated/monounsaturated/saturated
(P/M/S) ratio 0.2∶0.6∶1.0) than reference diets (P/M/S ratio 1∶1∶1) and this was true for both PE (33.4±1.0%vs 24.3±1.1%) and PC (9.3±0.5%vs 4.9±0.3%). Although suitable controls for cholesterol effects were not included in the study, earlier results obtained with
marmosets lead us to believe such effects were probably small. Regardless of basic diet (atherogenic, reference), 20∶5n−3
was preferentially incorporated into PE (10.8±0.2%, 6.0±0.02%) while smaller amounts were incorporated into PC (6.9±0.4%,
3.2±0.2%). The major n−3 polyunsaturated fatty acid found in PE in response to dietary 20∶5n−3 was the elongation metabolite
22∶5n−3 in both the atherogenic (17.7±0.7%) and reference (14.3±1.0%) dietary groups; 22∶6n−3 levels were less affected by
diet (4.7±0.3% and 3.9±0.2%, respectively). The results can be interpreted to indicate an inverse relationship between the
amount of dietary 18∶2n−6 and incorporation of 20∶5n−3 into erythrocyte membrane phospholipids regardless of whether the major
dietary n−3 fatty acid was α-linolenate (18∶3n−3) or 20∶5n−3. This interpretation is supported by theoretical calculations. 相似文献
20.
Bertram I. Cohen Erwin H. Mosbach Naoguki Matoba Sung Ock Suh Charles K. McSherry 《Lipids》1990,25(3):143-148
Cholesterol gallstones were present in prairie dogs fed alfalfa plus corn with and without exogenous cholesterol (0.4%). The
diets fed to the animals for eight weeks contained alfalfa plus corn in fixed proportions of 50∶50, 85∶15 and 15∶85 (w/w).
At sacrifice, all animals were healthy but had not gained weight; no deaths occurred during the experiment. Cholesterol gallstones
were present in all groups. In the absence of exogenous cholesterol, the highest stone incidence was found in the animals
which received the lowest fiber (highest corn) diets (alfalfa plus corn, 50∶50, 67%; alfalfa plus corn, 15∶85, 83%). Cholesterol
gallstone incidence was 100% when exogenous cholesterol was added to the alfalfa plus corn diets (50∶50 and 15∶85). No pigment
gallstones were detected in any animal. Liver and plasma cholesterol concentrations were highest in the animals receiving
alfalfa plus corn (15∶85) plus 0.4% cholesterol (4.29 mg/g, and 356 mg/dl, respectively). These values were lowest in animals
receiving 85% alfalfa plus 15% corn without cholesterol (2.19 mg/g and 88 mg/dl, respectively). Lithogenic indices were below
1.00 in all groups. Biliary bile acids were mainly amidates of cholic acid and chenodeoxycholic acid, with the former predominating.
Thus, gallstones can be formed in prairie dogs in the absence of exogenous cholesterol; gallstone incidence is reduced by
dietary fiber. 相似文献