Biomedical subjects

C Lutton

Publications and source records attributed to C Lutton.

At least 37 records · Page 2Linked to original sources

PubMed1998

Effect of beta-cyclodextrin dietary supplementation on biliary proteins and their resulting cholesterol nucleating activity in pigs.

We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs.

Animals↗

PubMed1998

Improved assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by the use of hydroxypropyl-beta-cyclodextrin and an NADPH-regenerating system.

Cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis, has been implicated in atherosclerosis and gallstone disease. The aim of this study was to check if the use of hydroxypropyl-beta-cyclodextrin (HPBCD), a vehicle for solubilizing cholesterol, augmented the rate of 7 alpha-hydroxycholesterol formation in hamster liver microsomes compared to classical assays in which labeled cholesterol was delivered in Tween 80. We observed that [14C]cholesterol carried by HPBCD enhanced the sensitivity of the assay tenfold. However, linearity of 7 alpha-hydroxycholesterol formation with time was short because of the rapid transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one and 7 alpha,12 alpha-dihydroxy-cholesten-3-one when NADPH alone was present in the incubation medium. In order to avoid the transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one, which is essentially NAD(+)-dependent, but is also NADP(+)-dependent, NADPH (1 mmol/l) plus an NADPH-regenerating system must be present in the medium. In this improved assay, the optimal pH was 7.4 and the apparent Km for control and cholestyramine-fed hamsters had a similar value of 315 mumol/l; linearity in the formation of 7 alpha-hydroxycholesterol was also apparent after a relatively short time period (10 min), but with a markedly greater slope of the curve. With a short incubation time (6 min), microsomes from livers of hamsters (five and nine weeks old) that were fed with a commercial ground diet yielded rates of 7 alpha-hydroxycholesterol formation of 115 +/- 10 and 150 +/- 16 pmol/min.mg protein, respectively, whereas microsomes from hamsters fed with a lithogenic sucrose-rich diet (five weeks old) yielded rates of 7 alpha-hydroxycholesterol formation of 77 +/- 7 pmol/min.mg protein, which were significantly lower (-33%) than those of corresponding control hamsters. This improved cholesterol 7 alpha-hydroxylase assay is very sensitive, simple and rapid, and does not necessitate sophisticated equipment. It can be particularly useful for determining cholesterol 7 alpha-hydroxylase activity in liver biopsies from dyslipidemic or lithiasic patients.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1998

Effects of insulin deficiency on lipoproteins and their hepatic receptors in Rico rats.

The present study was designed to examine the effect of streptozotocin (STZ)-induced diabetes on the plasma lipoprotein profile and hepatic expression of the LDL receptor and HDL binding protein (HB2) in hypercholesterolemic Rico rats. The plasma level of HDL1 (density range 1.040-1.063), which is particularly high in this rat strain, decreased (-25%) 28 d after STZ administration (50 mg/kg). In contrast, the treatment increased (+54%) the plasma concentration of HDL2 (density range 1.063-1.210). These variations in the lipoprotein concentrations were associated with inverse changes in the hepatic protein levels of the LDL receptor (+118%) and HB2 (-46%). These results suggest that the hepatic expression of HB2, a putative HDL receptor, can influence the plasma level of apo Al-rich HDL as has already been shown for the LDL receptor for apo B/E containing lipoproteins.

Animals↗

PubMed1998

The diurnal rhythms of cholesterol metabolism and plasma clearance of model chylomicrons: comparison of normal and genetically hypercholesterolemic rats (RICO).

Previous studies showed a slower clearance of cholesterol-labeled lymph chylomicrons in genetically hypercholesterolemic rats (RICO) compared with normocholesterolemic rats. In this study, we compared rates of lipolysis and remnant clearance in RICO versus control normocholesterolemic rats of the same strain (RAIF) or with control Wistar rats, by injecting chylomicron-like lipid emulsions labeled with 14C-triolein to trace lipolysis, and 3H-cholesteryl ester to trace remnant clearance. Our findings showed slower clearance of chylomicron remnants in RICO compared with control RAIF or with control Wistar rats. During the light period, the clearance of lipids from chylomicron-like lipid emulsions injected intravenously was significantly slower in RICO rats compared with normocholesterolemic control rats of the same strain, RAIF. Within the RICO group, clearance of emulsion triolein (TO) was faster during the dark period compared with the light period. In contrast, however, the clearance of the emulsion remnants traced by cholesteryl oleate (CO) was slower during the dark period. This behaviour was not found within the Wistar group, where the clearances of TO and CO were similar in the light and dark period. Hepatic clearance of chylomicron remnants is mediated primarily by the low density lipoprotein (LDL) receptor, the expression of which shows diurnal variation. In both Wistar and RICO rats, the expression of LDL receptors was highest during the dark period. The LDL receptors in hepatic microsomal membranes from RICO rats migrated faster on SDS polyacrylamide gel electrophoresis when compared with normal Wistar and the RAIF. However in hepatic plasma membranes the LDL receptors from RICO and Wistar rats appeared identical after immunoblotting. Furthermore the LDL receptors from RICO and Wistar rats responded similarly to treatment with neuraminidase. An alteration in post-translational processing of the LDL receptor could possibly account for the slower clearance of chylomicron remnants in the RICO.

Animals↗

PubMed1998

Effects of ionizing radiation (neutrons/gamma rays) on plasma lipids and lipoproteins in rats.

Male Wistar rats weighing 250 g were exposed to 4 Gy of neutrons/gamma radiation (3.33 Gy of neutrons and 0.66 Gy of gamma rays). After whole-body irradiation, plasma cholesterol and phospholipid levels increased up to 62 and 37%, respectively, at day 4 and then returned to control values 12 days after irradiation. Plasma triglyceride concentrations decreased concomitantly with decreased food intake after irradiation but remained higher than in pair-fed control rats. Plasma lipoproteins were separated by ultracentrifugation on a density gradient (1.006-1.210 g/ml). Four days after irradiation, most of the cholesterol (62% compared to 31% in controls, P < 0.001) is transported by apolipoprotein E-rich high-density lipoproteins. At the same time, plasma levels of apolipoproteins B and E were increased by 28 and 65%, respectively, while those of apolipoproteins AI and AIV were reduced by 21 and 59%, respectively. While in the liver of irradiated rats the apolipoprotein B/E receptor number was not modified, the hydroxymethylglutaryl coenzyme A reductase activity was fivefold higher than in control pair-fed rats. Four days after irradiation, the susceptibility of lipoproteins to peroxidation, as measured by the formation of conjugated dienes in the presence of Cu2+, was markedly increased while plasma vitamin E levels were decreased, demonstrating that irradiation reduces antioxidant stores markedly. These results suggest that such modified lipoproteins could be involved in radiation-induced vascular damage.

Animals↗

PubMed1997

Reduced cholesterol absorption in hamsters by crilvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Crilvastatin, a new drug from the pyrrolidone family, has been previously shown to inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in vitro and in vivo, to reduce the absorption of dietary cholesterol and to stimulate the activity of cholesterol 7 alpha-hydroxylase in the rat. The aim of this study was to evaluate the effects of crilvastatin on cholesterol and bile acid metabolism in the hamster. In hamsters fed on a lithogenic diet for 8 weeks, crilvastatin treatment (200 mg/day per kg body weight) did not change plasma lipid levels, failed to improve bile parameters and did not prevent gallstone formation. In hamsters fed on a basal cholesterol-rich (0.2%) diet for 8 weeks, crilvastatin at the same dose reduced the cholesterol level in the plasma by 20%, with a decrease of both low-density and high-density lipoprotein cholesterol. The drug did not significantly stimulate the biliary secretion of bile acids but significantly decreased the activity of acyl coenzyme A:cholesterol acyltransferase in the small intestine by 64%. This effect was enhanced when cholestyramine, a bile acid-sequestering resin, was given in combination with crilvastatin. Crilvastatin alone did not change the activity of cholesterol 7 alpha-hydroxylase in the liver, despite the marked reduction in both hepatic cholesterogenesis and intestinal absorption of dietary cholesterol (the absorption coefficient was 44 +/- 2% in treated hamsters vs. 61 +/- 7% in controls).

Animals↗

PubMed1997

Determination of molecular associations of some hydrophobic and hydrophilic bile acids by infrared and Raman spectroscopy.

The aim of this study was to analyse the Raman and infrared spectra of eight common mammalian bile acids in order to identify intermolecular interactions between hydroxyl and carbonyl groups. The results are considered in the light of the new hydrophilic/hydrophobic classification of bile acids. The alcohol OH group of the hydrophobic bile acids forms different intermolecular bonds. The most hydrophobic bile acid, lithocholic acid forms polymers, and this may explain its very low water solubility. The hydrophilic bile acids have some of their alcohol OH groups free of any intermolecular interaction. The strongly hydrophilic murideoxycholic acid also forms dimers, again consistent with a very low water solubility. The proposed structural arrangements are in agreement with published crystallographic studies.

Animals↗

PubMed1997

Inducing cholesterol precipitation from pig bile with beta-cyclodextrin and cholesterol dietary supplementation.

BACKGROUND/METHODS: In this study, pigs fed for 3 weeks a well-balanced semi-purified diet enriched with 0.3% cholesterol and 0, 5 or 10% beta-cyclodextrin were proposed as new animal donors of gallbladder bile exhibiting different rates of cholesterol crystallization, in order to gain insight into the early mechanisms underlying cholesterol precipitation in vivo. The appearance and growth of cholesterol crystals were monitored in the incubated freshly collected gallbladder biles through light microscopy and concomitant time-sequential determination of crystallized cholesterol concentration, and interpreted in terms of the composition of the bile. RESULTS: Although the concentration of total lipids and proteins and the relative proportions of bile acids, phospholipids, and cholesterol remained unchanged under beta-cyclodextrin, the cholesterol crystallization increased in the following order: 0<<10<5% beta-cyclodextrin. Concomitantly, the proportion of chenodeoxycholic acid in bile, and the hydrophobicity index of the biliary bile acid mixture increased in the following order: 0<5<10% beta-cyclodextrin (the same as reported elsewhere for the decrease in the antinucleating ApoA1), while sn-2 arachidonoyl biliary lecithins were specifically increased with 5% beta-cyclodextrin in the diet. CONCLUSIONS: We hypothesized that lecithin molecular species may be the determinant factor in modulating high cholesterol crystallization rates in biles otherwise enriched with hydrophobic bile acids.

Animals↗

PubMed1997

Determination of hepatic acyl-coenzyme A-cholesterol acyltransferase activity in LPN hamsters: a model for cholesterol gallstone formation.

Acyl-coenzyme A-cholesterol acyltransferase (ACAT) catalyses the esterification of cholesterol with long-chain fatty acyl-coenzyme A derivatives and has been implicated in the development of cholesterol gallstones. In this study we have examined several key components of the hepatic ACAT assay in order to develop a reliable and sensitive ACAT assay for LPN hamsters, a breed of golden Syrian hamster which has been characterized recently by this laboratory as a particularly good model for studying the pathogenesis of cholesterol gallstones. The newly developed ACAT assays were subsequently used to examine whether hepatic ACAT activity is altered in this animal model. Important new methodological findings were: (i) ACAT activity displayed two pH optima, one at 7.0 when assayed using endogenous cholesterol as substrate, and the other at about pH 8.5-9.0 when assayed in the presence of exogenous cholesterol; (ii) ACAT activity increased markedly when exogenous cholesterol was delivered to ACAT in Tween 80 (125-fold) or hydroxypropyl-beta-cyclodextrin (200-fold) in contrast to the use of cholesterol/phosphatidylcholine liposomes (9-fold); (iii) the addition of dithiothreitol, but not reduced glutathione, to the assay mixture resulted in a marked decrease in ACAT activity. Using the optimal assay conditions (exogenous cholesterol added), hepatic ACAT activity was shown to be significantly reduced in hamsters fed a high sucrose lithogenic diet compared with controls (587+/-42 vs 737+/-44 pmol/min per mg; P=0.025). In contrast, ACAT activity measured using endogenous cholesterol as a substrate was greater in sucrose-fed hamsters compared with controls (22.3+/-2.5 vs 13.2+/-2.9 pmol/min per mg; P= 0.030). These results highlight the importance of using an ACAT activity assay which has been well characterized and supports the hypothesis that the pathogenesis of cholesterol gallstones in LPN hamsters is related to an altered hepatic cholesterol metabolism.

Animals↗

PubMed1997

Hypocholesterolemic action of beta-cyclodextrin and its effects on cholesterol metabolism in pigs fed a cholesterol-enriched diet.

To examine the effects of beta-cyclodextrin (BCD), a non-absorbable carbohydrate, on lipid metabolism, growing pigs were fed a 0.3% cholesterol-enriched diet for 4 weeks or this diet containing 5% or 10% BCD. Pigs fed a basal diet without added cholesterol or BCD were used as controls. The cholesterol-rich diet induced hypercholesterolemia (1.75 vs. 0.84 g/l plasma) due to increased LDL concentration, delayed the plasma clearance of vitamin A, enhanced liver cholesterol storage, lowered the hepatic activities of LDL-receptors (by 47%) and HMG-CoA reductase (by 62%), stimulated cholesterol 7alpha-hydroxylase (x3), and accelerated the fecal output of neutral sterols (x4). Addition of BCD to the cholesterol-rich diet prevented the elevation of plasma cholesterol due to dietary cholesterol excess. Moreover, BCD produced a dose-dependent effect in reducing liver cholesterol storage, stimulating hepatic cholesterogenesis, increasing the proportion of primary bile acids in bile and in feces, and the fecal loss of neutral sterols and bile acids. Pigs receiving 10% BCD thus differed markedly from controls, especially for HMG-CoA reductase and cholesterol 7alpha-hydroxylase hepatic activities (x5), and fecal output of total bile acids (x3) and hyocholic acid (x20), and their overall cholesterol synthesis was higher (+50%), despite the abundant dietary cholesterol. Owing to the property of BCD to bind cholesterol and bile acids in vitro, these results suggest that this resistant carbohydrate accelerates body cholesterol turnover by reducing cholesterol absorption, increasing cholesterol and bile acid synthesis, and altering the action of the intestinal microflora.

Animals↗

PubMed1996

Metabolism of plasma lipoproteins in the genetically hypercholesterolemic rat (RICO).

Experiments were performed to determine the turnover processes of plasma cholesterol in genetically hypercholesterolemic rats (RICO). Specific activity of plasma cholesterol was monitored during 4 months following an intravenous injection of tritiated cholesterol. The results were subjected to two-pool model analysis. Cholesterol production in the RICO rat was significantly higher (28.9 +/- 1.7 mg/d) than in the SW control (18.5 +/- 0.7, P < .01). The study also revealed a 30% decrease in the rate constant for cholesterol movement from the plasma toward the majority of organs in the RICO rat versus the SW control. Very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) turnover were investigated following injection of labeled lipoproteins (on cholesteryl ester or apolipoproteins). Results from these experiments showed that the higher HDL cholesterol concentration in the RICO rat as compared with the control is due to the greater production rate of esterified cholesterol in these lipoproteins (1.3 +/- 0.05 mg/h v 0.8 +/- 0.03 in the control, P < .001). The fractional catabolic rate (FCR) or production rate for VLDL were not significantly different between the two groups (3.4 +/- 0.01 and 3.6 +/- 0.01 h-1 and 2.6 +/- 0.4 and 3.3 +/- 0.1 mg/h, respectively). However, radioactivity of VLDL recovered in LDL at death was considerably higher in RICO rats (14% +/- 1% v 6% +/- 1%, P < .01). The greater concentration of LDL cholesterol in RICO rats is due to a higher LDL production (0.40 +/- 0.05 v 0.19 +/- 0.03 mg/h, P < .01) together with a lower catabolism (FCR, 5.5 +/- 0.6 v 7.9 +/- 0.8%/h, P < .05). Cross-injection experiments showed that this lower catabolism of LDL is partly due to the nature of the lipoprotein particle. Taken together, these data are consistent with the hypothesis of a reduced uptake of apolipoprotein (apo)E-containing lipoproteins (VLDL and LDL), which results in a higher LDL cholesterol concentration in RICO rats.

Animals↗

PubMed1996

Anatomical heterogeneity of the intestinal mucosa and cholesterol homeostasis. A review of studies with normal and genetically hypercholesterolemic (RICO) Rat.

Quantitative data on cholesterol movements in mucosa cell as a function of its localization in the small intestine have been obtained in normocholesterolemic (SW) or genetically hypercholesterolemic (RICO) rats. Bile cholesterol absorption is greater and more proximal than dietary cholesterol absorption, both taking place mainly in the top cells of the duodenum or the proximal jejunum. Esterification of cholesterol also takes place mainly in the villus cells, while cholesterol synthesis is predominantly carried out in the crypt cells of the proximal duodenum and distal ileum. Cholesterol exchanges, which replace half of the cell cholesterol through the cell life, can be estimated at 3-4%.h-1 between plasma and mucosa cells, according to its location, i.e. 12-25 micrograms.h-1 (per mg cell DNA). In comparison, the cholesterol HDL or LDL uptake appears to be very low (0.02-0.06 and 0.2-0.6 microgram.h-1, respectively). Compartmentalization of cholesterol metabolism in the enterocyte can be suggested by different experimental data. The turnover of newly synthesized cholesterol is about 2-fold lower than that of exogenous (dietary) cholesterol.

Animals↗

PubMed1995

Crilvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, inhibits cholesterol absorption in genetically hypercholesterolemic rats.

Crilvastatin is a new drug from the pyrrolidone family, which acts as a non-competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The long-term effects of oral crilvastatin treatment (200 mg per day per kg body weight for 4 and 10 weeks) were investigated on in vivo cholesterogenesis in male adult normocholesterolemic (SW) and genetically hypercholesterolemic (RICO) rats. In both strains of rats, the treatment had no effect on the plasma cholesterol level, but efficiently inhibited cholesterol synthesis in liver and intestine, as shown by the decreased incorporation of exogenous [14C]acetate into hepatic (3.5-fold in SW, 1.7-fold in RICO rats) and intestinal (2.5-fold in SW, 3.3-fold in RICO rats) sterols. In RICO rats in which the dietary cholesterol absorption coefficient was two-fold lower in treated (38%) than in untreated (78%) rats, this drug reduced intestinal cholesterol absorption. As a result, the total plasma cholesterol input (absorption + synthesis), measured by isotope analysis in RICO rats, was markedly lower in treated (11.3 mg per day) than in untreated animals (28.8 mg per day).

Absorption↗

PubMed1995

Total parenteral nutrition stimulates hepatic cholesterol synthesis in the rat.

Cholesterol synthesis was studied in parenterally fed rats, as compared to orally fed rats with or without saline infusion. Conditions of total parenteral nutrition (TPN) involved the intravenous infusion of a nutritive mixture containing 20% Intralipid as the lipid source (50% of non-protein energy) at the continuous rate of 2 ml per h, for five days. In rats maintained in isotopic steady state by daily injections of [3H]cholesterol, isotope dilution indicated that the endogenous plasma cholesterol input was significantly higher (+15%, P < 0.05) in TPN than in orally fed rats, which suggested a slight stimulation of whole body cholesterogenesis. Cholesterol synthesis was assessed in TPN and orally fed rats by the in vivo incorporation of [1,2-13C]- and [1-14C]acetate into hepatic and intestinal sterols, and by the activity of HMG-CoA reductase in microsomes isolated from liver and small intestine. Both methods demonstrated that TPN markedly stimulated the hepatic cholesterol synthesis, since the radioactivity of liver sterols was 6- to 10-fold higher, and the activity of HMG-CoA reductase 5-fold higher, in TPN than in orally fed rats. Despite the weight reduction of the small intestine, by about 20% after TPN, the incorporation of exogenous [14C]acetate into intestinal sterols was similar in TPN and orally fed rats. As the liver and intestine are the main organs responsible for the appearance of endogenous cholesterol in plasma, it may be concluded that the increased endogenous plasma cholesterol input was mainly due to a strong stimulation of hepatic cholesterol synthesis in TPN rats.

Animals↗

PubMed1995

Effects of hyodeoxycholic acid and alpha-hyocholic acid, two 6 alpha-hydroxylated bile acids, on cholesterol and bile acid metabolism in the hamster.

The effects of hyodeoxycholic (HDCA) and alpha-hyocholic acids (alpha-HCA), on cholesterol, bile acid and lipoprotein metabolism, were studied in hamsters. The animals were fed a low cholesterol control diet supplemented with 0.1% HDCA or alpha-HCA for 3 weeks. In both treated groups, the LDL-cholesterol concentration was significantly lowered and was associated with a global hypocholesterolemic effect. Moreover, hepatic cholesterol ester storage was reduced and HMGCoA reductase activity was respectively enhanced 13.5-times and 7.7-times in HDCA and alpha-HCA groups compared to controls. In contrast, cholesterol 7 alpha-hydroxylase activity and LDL-receptor activity and mass were not modified. In bile, the cholesterol saturation index was increased 5-fold (HDCA group) and 2-fold (alpha-HCA group) as a consequence of an enlarged proportion of biliary cholesterol. The two 6-hydroxylated bile acids induced an enhanced fecal excretion of neutral sterols (HDCA group: 11.6-times, alpha-HCA group: 3.2-times versus controls) which was consistent with a 59% decrease in intestinal cholesterol absorption in the HDCA group. The major effects due to bile acid treatments were a decrease in LDL-cholesterol concentration, a strong stimulation of hepatic cholesterol biosynthesis and an excessive loss of cholesterol in feces. These perturbations might be the result of the enrichment of bile with hydrophilic bile acids, leading to a limited return of endogenous cholesterol from the intestine to the liver.

Animals↗

PubMed1995

Antilithiasic and hypocholesterolemic effects of diets containing autoclaved amylomaize starch in hamster.

The prevention of cholelithiasis by dietary manipulation was investigated in hamsters receiving a fat-free lithogenic (L) diet or this diet in which sucrose was replaced by 12 (group AS12), 36 (group AS36), 48 (group AS48), or 72.5% (group AS72.5) of autoclaved amylomaize starch for seven weeks. All hamsters (6/6) had cholesterol gallstones in groups L and AS12, while only 3/6 hamsters in group AS36 had gallstones. None were present in groups AS48 and AS72.5. Except in group AS12, biliary cholesterol level and lithogenic index (LI) decreased significantly in hamsters receiving amylomaize starch. Plasma cholesterol concentration was reduced by 31 and 54%, respectively, in groups AS48 and AS72.5 as compared to group L. The concentration of esterified cholesterol in the liver was also reduced significantly in all groups receiving amylomaize starch. Hepatic cholesterogenesis was decreased by 74 and 65%, respectively, in groups AS48 and AS72.5 as compared to group L. The transformation of cholesterol to bile acids was increased in group AS72.5 (+152%) as compared to L, while fecal cholesterol excretion was strongly lowered (-31%). Amylomaize starch reduced the microbial transformation of cholesterol to coprosterol and epicoprosterol, and in group AS72.5 it decreased the degradation of cholic acid. Thus, this autoclaved amylomaize starch, which could be used in human nutrition, prevents cholelithiasis and lowers cholesterolemia.

Animals↗

PubMed1995

Hepatic apolipoprotein and LDL receptor gene expression in the genetically hypercholesterolemic (RICO) rat.

The present study was designed to examine apolipoprotein and LDL receptor gene expression in genetically hypercholesterolemic RICO rats. In the plasma of RICO rats as compared to SW (control) rats, the hypercholesterolemia (+41%) was associated with a significant increase in plasma apo B (+23%) and apo E (+68%) concentrations. Study of apolipoprotein synthesis in the liver has shown that this increase in plasma apo B and apo E concentrations was not associated with modification in their synthesis and mRNA levels. Study of apo E mRNA level in various tissues has shown only the modification in adrenals in RICO as compared to SW rats (2.7-fold increase). Study of LDL binding, LDL receptor mass and LDL receptor mRNA level in the liver of RICO and SW rats has shown no significant differences between these two strains. EDTA-resistant binding of rat LDL was lower in RICO than in SW rats suggesting that binding sites others than the LDL receptor are present in lesser amount in this hypercholesterolemic strain.

Adrenal Glands↗

PubMed1995

Magnetic resonance imaging for the visualization of cholesterol gallstones in hamster fed a new high sucrose lithogenic diet.

Cholesterol gallstone induction in hamster gallbladder is usually achieved by specific diets. An X-ray in vivo follow-up of cholelithiasis development in this species is impossible, since cholesterol gallstones are transparent as long as they are not calcified. Moreover, their size (0.2 to 1 mm) also prevents their detection by ultrasonography. The current study presents an in vivo cholesterol gallstone detection by magnetic resonance imaging in hamsters fed a new high sucrose diet containing a low proportion of cholesterol (0.015%) and a normal ratio of lipids (10%). The diet produced gallstones and an increase in the cholesterol saturation index in about 50% of animals after a 5-week feeding period. The visualization of gallstones by magnetic resonance imaging in anaesthetized animals required synchronization between breathing movements and image acquisition. A high magnetic field was also necessary to allow a fine image resolution, adapted to gallstone size. Two major advantages of this technique are a direct selection of lithiasic animals with a functional gallbladder (in spite of the presence of gallstones) and a possible adjustment of the treatment period of potential litholytic drugs.

Animals↗