Selenium nanoparticles inhibit the formation of atherosclerosis in apolipoprotein E deficient mice by alleviating hyperlipidemia and oxidative stress.

Atherosclerosis can cause severe cardiovascular diseases, which is the most common cause of death in the world. It's of great significance to study the prevention and treatment of atherosclerosis. Selenium nanoparticles (SeNPs) has drawn more and more attention due to high biological activity, high bioavailability, strong antioxidant capacity and low toxicity, exhibiting great potential in biomedical application. Thus, this study aimed at explore the anti-atherosclerotic effect of two kinds of SeNPs, bovine serum albumin (BSA) surface-decorated SeNPs and chitosan (CS) surface-decorated SeNPs (CS-SeNPs), in apolipoprotein E deficient (ApoE-/-) mice fed with a high-cholesterol and high-fat diet, and the possible mechanisms. The results demonstrated that both BSA-SeNPs (25, 50 and 100 µg Se/kg body weight/day) and CS-SeNPs (50 µg Se/kg body weight/day) could reduce atherosclerotic lesions in ApoE-/- mice after oral administration for 12 weeks. And these effects might mainly attributed to the ability of BSA-SeNPs and CS-SeNPs to inhibit hyperlipidemia by suppressing hepatic cholesterol and fatty acid metabolism, and alleviate oxidative stress by enhancing antioxidant activity. Moreover, the benefits of BSA-SeNPs were dose-dependent and the medium dose of BSA-SeNPs (50 µg Se/kg body weight/day) was optimal. Generally, BSA-SeNPs with mean size 38.5 nm and negative surface charge showed better anti-atherosclerotic effect than CS-SeNPs with mean size 65.8 nm and positive surface charge. These results suggested that SeNPs could significantly alleviate the formation of atherosclerosis in ApoE-/- mice, possibly by inhibiting hyperlipidemia and oxidative stress, exhibiting a potential to serve as an anti-atherosclerotic agent.

Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis.

BACKGROUND: There is a marked need for improved animal models of nonalcoholic steatohepatitis (NASH) to facilitate the development of more efficacious drug therapies for the disease. METHODS: Here, we investigated the development of fibrotic NASH in male Wistar rats fed a choline-deficient L-amino acid-defined (CDAA) diet with or without cholesterol supplementation for subsequent assessment of drug treatment efficacy in NASH biopsy-confirmed rats. The metabolic profile and liver histopathology were evaluated after 4, 8, and 12 weeks of dieting. Subsequently, rats with biopsy-confirmed NASH were selected for pharmacological intervention with vehicle, elafibranor (30 mg/kg/day) or obeticholic acid (OCA, 30 mg/kg/day) for 5 weeks. RESULTS: The CDAA diet led to marked hepatomegaly and fibrosis already after 4 weeks of feeding, with further progression of collagen deposition and fibrogenesis-associated gene expression during the 12-week feeding period. Cholesterol supplementation enhanced the stimulatory effect of CDAA on gene transcripts associated with fibrogenesis without significantly increasing collagen deposition. Pharmacological intervention with elafibranor, but not OCA, significantly reduced steatohepatitis scores, and fibrosis-associated gene expression, however, was unable to prevent progression in fibrosis scores. CONCLUSION: CDAA-fed rats develop early-onset progressive NASH, which offers the opportunity to probe anti-NASH compounds with potential disease-modifying properties.

Synthesis of lipid-black phosphorus quantum dot bilayer vesicles for near-infrared-controlled drug release.

Black phosphorus quantum dots are incorporated into liposomal bilayers to produce a drug delivery system with excellent near-infrared (NIR) photothermal properties and drug release capability controlled by light. In vitro experiments demonstrate its good biocompatibility and NIR-light-induced chemo-photothermal antitumor efficiency.

Taurine May Modulate Bone in Cholesterol Fed Estrogen Deficiency-Induced Rats.

Taurine is thought to affect bone in rats favorably. However, studies on the actions of this estrogen deficiency and high cholesterol diet factors on the bone metabolism are limited. In this study, the protective effect of taurine on bone was determined. Thirty-two 42 days old female SD rats were placed in individual stainless cages. Given to rats was fed to chow (Samyang Corporation, South Korea) and deionized water for a 4 days adaptation period. After the period of adaptation, Half of the rats were induced estrogen deficiency model by ovariectomy (OVX), and the left rats with sham-operated were used control (SHAM). For six weeks, the OVX and SHAM rats had separately a 2% taurine supplemented diet with ad libitum in both the water and the food. DEXA for small animals (PIXImus, GE Lunar co, Wisconsin) was used to determine spinal and femoral bone. The concentrations of serum calcium and phosphorus were also measured. The monitoring of bone formation was done by determining the serum ALP and osteocalcin. Urinary DPD the values were determined as index of bone resorption. Statistical measure was done with SAS (version 9.3). A lower overall intake of the daily food was observed in non-ovariectomized rats than in the OVX rats. At sacrifice, a much greater body weight was observed in ovariectomized group compare to non-operated group. That difference was absent in both fed taurine SHAM and OVX rats. Serum calcium and phosphorus were not statistically different by taurine supplementation. Urinary excretion of calcium was not effected by taurine supplementation. Serum ALP and was significantly decreased by taurine in OVX rats (p < 0.05). For the spine BMD and BMC, there was no difference among SHAM and OVX rats by taurine. Spine BMC per body weight of taurine groups were higher than control groups (p < 0.1). No significant difference was observed after taurine supplementation in femur BMD and BMC. The analysis of the results suggest that taurine supplementation modulates the bone mineral contents in postmenopausal model rats fed with high cholesterol diet.

Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic ß-Cells Function.

Cholesterol plays an important role in inducing pancreatic ß-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic ß-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic ß-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve ß-cell function and eventually control hyperglycemia.

Anti-obesity and lipid lowering effects of Cymodocea nodosa sulphated polysaccharide on high cholesterol-fed-rats.

This study aims to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo to high fat diet (HFD)-rats on body weight, lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats in serum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads to lipid regulation shown by the decrease of total cholesterol (T-Ch), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and an increase in high density lipoprotein cholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters in blood.

Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage.

Evaluation of the cytotoxic effect of 7keto-stigmasterol and 7keto-cholesterol in human intestinal (Caco-2) cells.

The biological implications of cholesterol oxidation products have been investigated, though research on plant sterol oxidation products is scarce and in some cases contradictory. The cytotoxicity of 7keto(k)-stigmasterol versus 7keto(k)-cholesterol at different concentrations (0-120 µM) and incubation times (4-24h), in intestinal epithelial cells (Caco-2 cells) was evaluated. The 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyl tetrazolium bromide and neutral red uptake tests, mitochondrial membrane potential (ΔΨm), and relative DNA and RNA contents in the cell cycle phases were determined. Possible interaction effects between 7k-derivatives or non-oxidized stigmasterol were monitored. Endo/lysosomal activity was not impaired by either oxide. 7k-cholesterol showed a deleterious effect upon the mitochondrial compartment after 24h of exposure (120 µM), as well as upon ΔΨm when incubated at all concentrations (12/24h). Only cells incubated with 7k-cholesterol (120 µM) exhibited a decrease in RNA proportion in the G1 population. The presence of 7k-stigmasterol or stigmasterol with 7k-cholesterol reduced the deleterious metabolic effects upon mitochondrial functionality and integrity and the distribution of RNA contents in G1 and G2 phases. A decrease in the G1 phase proportion was detected in cells exposed to mixtures, without alterations in RNA content. The results obtained indicate the absence of 7k-stigmasterol cytotoxicity in Caco-2 cells and its capacity to reduce 7k-cholesterol toxicity.

Deferiprone reduces amyloid-ß and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet.

Accumulation of amyloid-ß (Aß) peptide and the hyperphosphorylation of tau protein are major hallmarks of Alzheimer's disease (AD). The causes of AD are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing AD. Additionally, altered metabolism of iron may have a role in the pathogenesis of AD. We have previously demonstrated that cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit brain. However, the extent to which chelation of iron protects against this pathology has not been determined. In this study, we administered the iron chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day) significantly decreased levels of Aß40 and Aß42 as well as BACE1, the enzyme that initiates cleavage of amyloid-ß protein precursor to yield Aß. Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation of tau but failed to reduce reactive oxygen species generation. While deferiprone treatment was not associated with any change in brain iron levels, it was associated with a significant reduction in plasma iron and cholesterol levels. These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced AD pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron. We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced AD-like pathology.

Proinflammatory effect of cholesterol and its oxidation products on CaCo-2 human enterocyte-like cells: effective protection by epigallocatechin-3-gallate.

Cholesterol and its oxidation products, namely oxysterols, have very recently been shown to potentially interfere with homeostasis of the human digestive tract, by promoting and sustaining irreversible damage of the colonic epithelial layer. This report concerns the strong proinflammatory action that a dietary oxysterol mixture and, to a lesser extent, an identical concentration of unoxidized cholesterol exert on CaCo-2 colonic epithelial cells by up-regulating both expression and synthesis of interleukin 8. The oxysterol mixture and its most effective component, 7ß-hydroxycholesterol, are also shown to markedly enhance the expression of key inflammatory and chemotactic cytokines in colonic epithelial cells, more efficiently than unoxidized cholesterol. The sterols' proinflammatory effect seems to be mediated by enhanced activation of NOX1, because it is prevented by pretreatment of the cells with DPI, a selective inhibitor of this oxidase. Importantly, NOX1 hyperactivation by the oxysterol mixture or cholesterol was fully prevented by CaCo-2 cell preincubation with epigallocatechin-3-gallate. Consistently, supplementation with this compound fully protected colonic epithelial cells against overexpression of inflammatory and chemotactic genes induced by the sterols investigated.

Changes in the brain cortex of rabbits on a cholesterol-rich diet following supplementation with a herbal extract of Tribulus terrestris.

Extracts of the medicinal herb Tribulus terrestris (TT) are used for treating various diseases. The saponins, a component of TT, play a role in regulating blood pressure and in treatment of hyperlipidemia. The aim of the study was to investigate the immunohistochemical and ultrastructural alterations in the cerebral cortex of experimental rabbits on a cholesterol rich diet treated with TT. The rabbits were divided into three groups and followed for 12 weeks as control group (CG); experimental group I (EG-I), fed with a cholesterol-rich diet; experimental group II (EG-II), treated with an extract of TT (5 mg/kg/day) after a cholesterol-rich diet of 4 weeks. In EG-I there were ultrastructural changes, including mitochondrial degeneration, increased lipofuscin pigments, myelin sheath damage with axoplasmic shrinkage and electron dense granules in the neurovascular unit. The number of synapses apparently decreased in both experimental groups. Administration of TT extract in EG-II led to marked ultrastructural alterations in neurons, including decreased mitochondrial degeneration (P<0.001) and extensive oedematous areas in the neurovascular unit. However, in EG-II, lamellar myelin, axonal structures and mitochondria were well protected. These alterations possibly indicate that saponins have an effect on the neurons either directly or by its conversion to steroidal saponins. Therefore, these findings add further evidence supporting the protective claims of TT in cerebral architecture in dietary induced hyperlipidemia.

[The state of ferment systems, participating in cholesterole metabolism: the influence of hepatotropic means under food hypercholesterolemia].

The studies, conducted on mice and rats with experimentally obtained hypercholesterolemia. Revealed that hepatotropic means of animal and plant origin--hepathosan, entherosan, karsil and alcohol, rich in biologically active substances, make for acceleration of cholesteroles hydroxylation in liver and increase of Hmger genes expression level up to planned indices. It was determined that hepathosan has the strongest modulating effect among hepatotropic means.

Effect of selenium compounds on the damage induced by oxysterol on rat arterial walls.

Wistar rats were fed Se-deficient (0.017 +/- 0.002 mg Se/kg) and Seadequate (0.32 +/- 0.045 Se mg/kg) diets for 12 mo and then were given 5 mg/kg of cholestane-3beta,5alpha,6beta-triol (3-triol), intravenously. Se compounds (Na(2)SeO(3) and ebselen) were supplemented in different doses and times to the Se-deficient rats. Twenty-four hours after 3-triol infusion, the changes in ultrastructures of rat aorta were examined by scanning electron micrography (SEM) and transmission electron micrography (TEM). SEM examinations showed that 3-triol induced diffused injuries on arterial endothelial urfaces of long-term Se-deficient rat, and a large number of holes or craterlike defects were observed. TEM examinations further showed that 3-triol induced swelling, necrosis, and shedding of endothelial cells, which resulted in the destruction of endothelial integrity. Meanwhile, smooth muscle cells proliferated and migrated toward intimae; the breakage of internal elastic lamina benefited the migration of smooth muscle cells. Supplemented with Na(2)SeO(3) (40 microg/kg, 10 d per continuum) and ebselen (20 mg/kg), respectively, exhibited significant protection from damages induced by 3-triol. It seems that protecting mechanisms were different between Na(2)SeO(3) and ebselen. The present investigation gave visual evidence that both injuries induced by cholesterol oxides and the Se nutritional status contributed to the development of atherosclerosis.

Toxicity of cholesterol oxidation products to Caco-2 and HepG2 cells: modulatory effects of alpha- and gamma-tocopherol.

Cholesterol can be oxidized to form a variety of cholesterol oxidation products also known as oxysterols. The aims of the present study were to compare the cytotoxic effects of four oxysterols, namely 25-hydroxycholesterol (25-OHC), 7beta-hydroxycholesterol (7beta-OHC), cholesterol-5beta,6beta-epoxide (beta-epox) and cholesterol-5alpha,6alpha-epoxide (alpha-epox), in two human cell culture models. Further, the ability of 10 and 100 micro m alpha- and gamma-tocopherol (alpha-TOC and gamma-TOC, respectively) to protect against oxysterol-induced cytotoxicity was also assessed. Human colonic adenocarcinoma Caco-2 and human hepatoma HepG2 cells were supplemented with increasing concentrations of 25-OHC, 7beta-OHC, beta-epox and alpha-epox (0-25 micro g ml(-1)) for 24, 48 or 96 h. Following 24-h and 48-h exposure, test media were replaced with normal growth media and the cells were maintained for 72 and 48 h, respectively. The 96-h exposure represented a constant challenge to the cells. Cytotoxicity was assessed using the neutral red uptake assay. The concentration of compound that inhibited cell viability by 50% (ic(50) value) was calculated. All four oxysterols investigated induced the greatest cytotoxic effects following 96 h of exposure. 25-Hydroxycholesterol exhibited the greatest cytotoxicity in both cell lines. Both beta-epox and alpha-epox were more toxic to HepG2 cells than to Caco-2 cells after the 48-h exposure. Pretreatment of cells with either alpha- or gamma-TOC did not protect against oxysterol-induced cytotoxicity. The caco-2 cells treated with the high concentration (100 micro m) of gamma-TOC were found to be more susceptible to oxysterol-induced toxicity under the conditions employed in this study.

Evaluation of the cytotoxic effects of some oxysterols and of cholesterol on endothelial cell growth: methodological aspects.

The effects of various oxysterols (7 beta-hydroxycholesterol, 7-ketocholesterol, 19-hydroxycholesterol, cholesterol-5 alpha, 6 alpha-epoxide, and 25-hydroxycholesterol) and of cholesterol were investigated on cell growth of bovine aortic endothelial (BAE) cells by cell counting, MTT reduction, and 3H-thymidine incorporation in a 5 to 80 micrograms/ml concentration range. By cell counting, a dose related decrease in the number of adherent cells was observed with oxysterols; MTT reduction also indicated a decreased number of viable cells, and both method give similar IC50. A lower 3H-thymidine incorporation was generally detected with oxysterols but no effect on 3H-thymidine incorporation was found with 25-hydroxycholesterol. With cholesterol, no modification of cell growth was shown by cell counting and 3H-thymidine incorporation, whereas an important decrease in MTT reduction was observed. Noteworthy, with the highest cholesterol concentration no change in cellular morphology occurred, and no modification of mitochondrial activity was found with Rhodamine 123. It is concluded that MTT and 3H-thymidine incorporation are not suitable for the evaluation of a putative toxicity of cholesterol and 25-hydroxycholesterol, respectively. Therefore, cell counting seems the most accurate method to determine the effects of oxysterols and of cholesterol on endothelial cell growth.

Roles of multiple oxidized LDL lipids in cellular injury: dominance of 7 beta-hydroperoxycholesterol.

The relative toxicities of several lipid oxidation products formed on oxidized LDL, their presence on oxidized LDL, and potential mechanisms of cell injury compared to oxidized LDL were examined. Toxicities to fibroblasts, with lipoprotein-deficient serum supplementation, were: 7 beta-hydroperoxycholesterol > 7 beta-hydroxycholesterol = 4-hydroxynonenal > 7-ketocholesterol > 5 alpha, 6 alpha-epoxycholesterol. Lysophosphatidylcholine was only significantly cytotoxic in the absence of lipoprotein-deficient serum. Without serum, relative toxicities were: 7 beta-hydroperoxycholesterol > lysophosphatidylcholine > 4-hydroxynonenal > 7 beta-hydroxycholesterol. Similar relative potencies were observed in smooth muscle and endothelial cell cultures. 7 beta-Hydroperoxycholesterol accumulated on oxidized LDL to greater amounts than other oxysterols and 4-hydroxynonenal, but less than lysophosphatidylcholine. Cell injury by 7 beta-hydroperoxycholesterol and oxidized LDL was inhibitable by antioxidants but not by exogenous cholesterol or cycloheximide. In contrast, a) toxicities by 7 beta-hydroxycholesterol, 7-ketocholesterol, 5 alpha, 6 alpha-epoxycholesterol, and 4-hydroxynonenal were not inhibited by antioxidants; b) 7 beta-hydroxycholesterol and lysophosphatidylcholine toxicities were inhibited by exogenous cholesterol; and c) 7 beta-hydroxycholesterol toxicity was inhibited by cycloheximide. Injury by lysophosphatidylcholine was reduced by vitamin E and not affected by altering the cellular exposure to selenium; reduced selenium enhanced toxicity by oxidized LDL and 7 beta-hydroperoxycholesterol. The high relative toxicity of 7 beta-hydroperoxycholesterol, the level of its accumulation on oxidized LDL, and its mechanism of action similar to oxidized LDL suggest that it is the compound predominantly responsible for oxidized LDL induced cytotoxicity.

The effect of isradipine administration on existing fatty streaks in the cholesterol-fed rabbit: a morphometric study.

Previous studies have shown that the administration of certain calcium channel blocking drugs (at an appropriate time point) can reduce the severity of atherosclerotic lesion formation. This study was undertaken to determine if the administration of isradipine would reverse established lesions produced by feeding rabbits an atherogenic diet. Rabbits were fed cholesterol for three weeks and examined directly, or after being left for a four week washout period, with or without a daily oral supplement of isradipine. Fatty streaks were well established after three weeks of cholesterol feeding and were more extensive at the end of the washout period, as indicated by gross changes in the volume of the intima per unit length of aorta. When isradipine was administered during the washout period, the volume of the intima per unit length of aorta fell to levels below those produced by cholesterol feeding for three weeks alone. The major components of the lesions affected to accommodate these changes were the foam cells and myointimal cells; these were examined in detail using morphometry and lipid cytochemistry. The mean volume of intima/cm of aorta occupied by foam cells and myointimal cells both fell by more than 60% to levels lower than those found after three weeks of cholesterol feeding alone. The volume of the extracellular space of the intima occupied by cytochemically demonstrable unesterified and esterified cholesterol was reduced by isradipine administration as was that of foam cells, all to levels lower than those found after three weeks of cholesterol feeding alone. These data indicate that the administration of isradipine during a washout period, after cholesterol feeding, can promote the regression of fatty streak lesions.

The effects of intravenous Triton WR-1339 on factor VII coagulant activity and plasma lipoproteins in normocholesterolaemic and hypercholesterolaemic rabbits.

The hypothesis that lipolysis of large lipoproteins by lipoprotein lipase (LPL) has an important influence on the activation of the contact system of coagulation and subsequently on factor VII activation was tested in rabbits rendered hyperlipidaemic by dietary means and/or by injection of Triton WR-1339. The dietary treatment involved a control diet and two isocaloric diets containing either a 0.5% cholesterol or 0.5% cholesterol and 7.5% safflower oil supplement. Other groups of rabbits were given either a standard diet or the standard diet supplemented with 1% cholesterol. All supplemented diets increased many-fold the concentrations of cholesterol associated with the chylomicron, very low-(VLDL), intermediate-(IDL) and low-density (LDL) lipoprotein fractions. Factor VII coagulant activity (FVIIc) increased significantly in all groups of rabbits fed the cholesterol supplement. The intravenous injection of Triton WR-1339 into rabbits fed either the standard or 1% cholesterol-supplemented diet resulted in increases of plasma cholesterol and triglyceride concentrations up to 36-48 h thereafter, followed by decreases up to completion of the experiment at 72 h. Most of these increases in plasma lipids were associated with the chylomicron and VLDL fractions. Following injection of Triton into rabbits fed either the standard or cholesterol-supplemented diet, changes in FVIIc were biphasic with a decrease in activity in the early intervals when rates of accumulation of plasma lipid were constant, and a progressive increase in activity at later intervals when rates of lipid accumulation declined and then reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocholesterolemic effect of vitamin E on cholesterol-fed rabbit.

Serum cholesterol level increased sharply in rabbits fed an atherosclerosis-promoting diet containing 0.25% or 0.5% cholesterol. Oral supplementation with 2100 IU of vitamin E per week manifested a hypocholesterolemic effect only after four weeks, with 50% reduction attained on the 8th week. Changes in low density and very low density lipoprotein cholesterol levels paralleled those in the serum. Liver total cholesterol level and the ratio of free to ester forms were not different between vitamin E-supplemented and nonsupplemented rabbits, whereas a 4-5 fold increase in hepatic cholesterol-7 alpha-hydroxylase activity, elevation of bile salt concentration and improvement in bile lithogenic index were observed in the vitamin E-supplemented groups.