Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets.

To study the influence of polymerised polyphenolics (PP), a fraction of silymarin (SM), on lipids and oxidant status, rats were fed high-cholesterol (1%), high-fat (10%) diets containing either lard fat (LFD) rich in saturated/monounsaturated fatty acids, or currant oil (COD) rich in polyunsaturated fatty acids. PP and SM were administered as dietary supplements (0.1-0.5-1.0%) for 3 weeks. PP (1%) decreased cholesterol (C) in VLDL (from 0.72+/-0.08 mmol l(-1) in LFD control to 0.35+/-0.07 mmol l(-1), P<0.01, and from 0.33+/-0.05 mmol l(-1) in COD control to 0.09+/-0.02 mmol l(-1), P<0.001), and increased HDL-C/VLDL-C ratio, however, without effect on the total plasma C and LDL-C. Liver C content (LFD 19.32+/-1.50 micromol g(-1), COD 18.64+/-2.13 micromol g(-1), N.S.) decreased after PP (1%) to 12.24+/-0.76 micromol g(-1), P<0.01, and 8.78+/-0.95 micromol g(-1), P<0.001, respectively. Triacylglycerols (TAG) in plasma and VLDL decreased after PP in the LFD group only, which displayed higher TAG levels than the COD group. Likewise, LFD caused a higher liver TAG content than did COD (31.16+/-3.00 micromol g(-1) versus 17.31+/-1.48 micromol g(-1), P<0.01), and PP (1%) decreased liver TAG only in rats fed LFD (19.55+/-2.43 micromol g(-1), P<0.02). Blood glutathione (GSH) increased after PP (1%) in the LFD group from 0.97+/-0.11 to 1.54+/-0.19 mmol l(-1) (P<0.05) and in the COD group from 0.58+/-0.15 to 1.23+/-0.10 mmol l(-1) (P<0.01), while liver GSH and plasma TBARS did not change. On principle, effects of PP were dose-dependent and parallel to SM. These results suggest that the polyphenolic fraction of SM positively modifies lipoprotein profile, counteracts the development of fatty liver and ameliorates an antioxidant status in circulation.     

Effect of hydroxycut intake on fasted and postprandial lipemia in rats

Hydroxycut, an herbal supplement not currently defined as a drug, is frequently sold over the counter to increase exercise performance, build muscles, and burn fat. The effects of 8 wk of hydroxycut-induced changes on blood lipid profile in rats fed with either regular or high-fat diet were evaluated. Regardless of fat content in the diet, the doses of hydroxycut used significantly decreased fasting serum concentrations of cholesterol, triacylglycerol (TAG), low-density lipoprotein (LDL) cholesterol, total apolipoprotein B (apo B), and LDL/high-density lipoprotein (HDL) cholesterol ratio. A significant increase in serum blood glucose level was observed with hydroxycut intake in the presence of a high-fat diet. No hydroxycut-related changes in serum activities of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate dehydrogenase (SGPT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK) enzymes were noted, indicating no liver damage occurred. A decrease in liver fat content was observed with hydroxycut intake. The drug did not affect the number and composition of secreted very-low-density lipoprotein (VLDL) particles except for a decrease in VLDL TAG when the fat content in the diet was high. Hydroxycut reduced significantly LDL apo B and LDL TAG and cholesterol concentrations. Hydroxycut increased TAG and cholesterol excretion in feces. A single intragastric food load containing hydroxycut reduced significantly postprandial plasma TAG concentration in a dose-dependent manner. In conclusion, hydroxycut intake in recommended doses exerts a beneficial impact on atherosclerosis, an effect attributed to improved clearance and metabolism of lipoprotein particles, and to a lesser extent to an increased excretion of TAG and cholesterol in the feces. More studies are needed to ensure the safety of long-term use of hydroxycut.     

Effect of acute and chronic moderate red or white wine consumption on fasted and postprandial lipemia in the rat

The effects of acute and chronic (10 wk) red or white wine consumption on fasted and postprandial lipemia in the rat model are reported. Fasted rats, in the acute study, were loaded intragastrically with 5 ml of an olive oil emulsion (30% w/v) in the presence or absence of wine (8% v/v ethanol), and either mesenteric lymph or blood was collected 3 h postprandially. Animals in the chronic study received either red or white wine in drinking water for a period of 10 wk (3% v/v ethanol). Blood samples were collected from animals in either the fasted state or after fat-wine loading. Postprandially, wine delayed gastric emptying, reduced lymph triacylglycerol (TAG) secretion concomitantly with increased number and decreased chylomicron (CM) size, and increased plasma TAG and CM concentrations. Phospholipid and cholesterol contents of CM, but not very-low-density lipoprotein (VLDL), were increased, indicating enhanced liver bile secretion; however, a significant increase in plasma VLDL concentration was observed. In the chronic study, a wine-fat load resulted in increased high-density lipoprotein (HDL) cholesterol concentration and less pronounced postprandial hypertriglyceridemia and hyperchylomicronemia. In the fasted state, plasma TAG and total apolipoprotein B concentrations were not modified in these animals, and an increase in HDL and a decrease in low-density lipoprotein (LDL)/HDL cholesterol ratios were observed. No liver function or intestinal lipid absorption impairment was observed. In conclusion, unlike binge drinking, chronic moderate wine consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.     

Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats.

The study tested the effects of phenolics-rich extracts from the plants Silybum marianum (silymarin) and Prunella vulgaris (PVE) on blood and liver antioxidant status and lipoprotein metabolism. Hereditary hypertriglyceridemic rats fed on standard diet (STD) or high-sucrose diet (HSD, 70cal% of sucrose) for two weeks were used. HSD doubled plasma and liver triacylglycerol (TAG) and increased plasma VLDL-TAG and VLDL-cholesterol compared to STD. Administration of silymarin or PVE as 1% dietary supplements in HSD did not influence lipid levels in plasma or liver, but both extracts caused decrease in plasma VLDL-cholesterol levels. HSD-induced oxidative stress was manifested in increased TBARS and conjugated dienes (CD) content, decreased GSH levels and glutathione peroxidase (GPX) activity in blood and liver. In blood the activity of superoxide dismutase (SOD) decreased, whereas in liver the activity of catalase increased after HSD. Feeding on HSD containing phenolics-rich extracts resulted in reduction of TBARS and CD content and in increase of blood GPX activity and elevated GSH content in liver. Besides, silymarin increased the activity of SOD and level of GSH in blood. Catalase activity in blood or liver was not influenced by the presence of plant extracts in the diet. These results indicate that silymarin and PVE improve antioxidant status in blood and liver and positively affect plasma lipoprotein profile in an experimental model of dietary induced hypertriglyceridemia.     

Effects of oleanolic acid and maslinic acid on hyperlipidemia

In the present study, we examined the therapeutic effects of pentacyclic triterpenes, oleanolic acid (OA) and maslinic acid (MA), on hyperlipidemia in a high‐cholesterol diet model. Hyperlipidemia was induced in male Sprague‐Dawley rats by feeding with a high‐cholesterol diet (HCD) for 30 days. MA and OA were supplemented (100 mg/kg body wt/day) during the last 15 days. The levels of serum total cholesterol (TC), triglyceride (TG), high‐density lipoprotein‐cholesterol (HDL‐C), and low‐density lipoprotein‐cholesterol (LDL‐C) increased in hyperlipidemic rats. An apparent increase in the expression of Acyl‐CoA cholesterol acyltransferase (ACAT) mRNA was seen in HCD‐fed rats. The activities of hepatic marker enzymes that serve as indices of cellular injury were also altered in HCD‐fed rats. Treatment with triterpenes modulated the abnormalities induced by hyperlipidimia. Lipid accumulation was decreased in histological findings. Elevated hepatic glycogen content (P<0.05) in triterpene groups was observed compared with HCD‐fed groups. Furthermore, ACAT gene expression was suppressed compared with hyperlipidemia‐induced groups without triterpenes. It can be concluded that triterpene treatment possesses therapeutic effects on diet‐induced hyperlipidemia by inhibiting the intestinal absorption and storage of cholesterol. Drug Dev Res 68:261–266, 2007. © 2007 Wiley‐Liss, Inc.     

Effect of acute and chronic moderate alcohol consumption on fasted and postprandial lipemia in the rat.

Effects of acute and chronic alcohol intake on fasted and postprandial lipemia in the rat model are reported. In the acute study, fasted rats are loaded with a 30% w/w olive oil emulsion with or without 8% alcohol in the form of ethanol, beer or whisky. After 3 h, either mesenteric lymph or blood is collected and the TAG-rich lipoprotein fractions are isolated. In the chronic study, animals received, for a period of 10 weeks, 3% alcohol in drinking water in the form of ethanol, beer or whisky. Blood samples were collected from animals in either the fasted state or after being loaded with the fat load as described above. Alcohol ingestion along with a fat load increases the number (increased net apoB48 secretion) and reduces the size (reduced TAG/apoB48 ratio) of CM secreted into the mesenteric lymph duct. It also delays gastric emptying, reduces trans-enterocyte TAG flux rates and increases plasma concentrations of TAG, cholesterol and CM. Similar conditions also results in increased total phospholipid and cholesterol content of CM but not of VLDL, indicating an enhanced liver bile secretion into the gut; however, a significant increase in plasma VLDL concentration is observed. Unlike the acute study, an alcohol-fat load in animals put on chronic alcohol intake results in increased HDL cholesterol concentrations and less pronounced postprandial hypertriglyceridemia and hypercholesterolemia but not hyperchylomicronemia. In the fasted state, plasma TAG and total apoB concentrations are not modified in these animals, and an increase in HDL and a decrease in total and LDL cholesterol concentrations are observed. No liver function impairment is observed following the 10-week period of chronic alcohol intake. In conclusion, unlike binge drinking, chronic moderate alcohol consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.     

Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis

This study was conducted to investigate the hypocholesterolemic effect of the hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis in a 5 l fermenter. The composition of HW was mainly carbohydrate (83.9%) and protein (11.8%) on a dry basis, and the carbohydrate of HW consisted of glucose, mannose, galactose, and arabinose in the molecular ratio of 1.0 : 0.8 : 0.5 : 0.1, respectively. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet, body and liver weights were not significantly different from those of the controls. The serum total cholesterol (TC) of all mice groups administered HW (150 and 300 mg/kg/d, respectively) with the cholesterol-enriched diet decreased more than in the control group. Among the mice fed the cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL) cholesterol level, but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL- and VLDL+LDL-cholesterol levels consequently decreased the atherogenic value. The results indicate that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol level. The 300 mg/kg dose had a significant effect on the serum TC level.     

Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats.

1. The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2. In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3. Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4. In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5. The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg-1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6. In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement bioavailability of silymarin ameliorates severe dyslipidemia associated with metabolic syndrome

Abstract

1. To compare the effectiveness of different drug forms of silymarin: standardized extract of silymarin (SS), micronized silymarin (MS) and silymarin in the form of phytosome (PS) on dyslipidemia and liver fat accumulation in a model of metabolic syndrome, in non-obese hereditary hypertriglyceridemic rats. The second aim of this study was to slightly uncover the silymarin action on enzymes and proteins involved in cholesterol metabolism and excretion.

2. Silymarin administered to hereditary hypertriglyceridemic rats as dietary supplements (1%) for 4 weeks significantly lowered the plasma levels of triglycerides, total cholesterol and markedly increased HDL cholesterol level. Western blot analyses showed significant increase in the protein expression of CYP7A1 and CYP4A and increase in protein expression of selected ABC transporters. Silymarin in the form of phytosome and micronized silymarin were more effective forms of silymarin.

3. These findings suggest that silymarin may favorably affect the metabolism of cholesterol and triglycerides in rats with metabolic syndrome. Raising HDL levels suggests potentially important anti-atherogenic effect of silymarin. The changes in expression of cytochromes P450 and ABC transporters involved in cholesterol metabolism and excretion could be partially responsible for the hypolipidemic effect of silymarin.     

The role of membrane composition in ATPase activities of cirrhotic rat liver: effect of silymarin

The activities of Ca2(+)- and Na+, K(+)-ATPases were studied in liver plasma membranes from CCl4-cirrhotic rats and from livers of rats treated with silymarin in addition to CCl4. CCl4 chronic treatment produced significant decreases in Na+, K(+)- and Ca2(+)-ATPase activities; however, the animals treated with silymarin along with CCl4 showed no differences in ATPase activities as compared to controls. The lipid analysis performed in plasma membranes revealed increases in the cholesterol/phospholipid (CH/PL) and sphingomyelin/phosphatidylcholine (SM/PC) ratios in the cirrhotic group. Again, the membranes isolated from rats receiving CCl4 + silymarin showed normal CH/PL and SM/PC values. Considering that CH/PL and SM/PC ratios are related to membrane microviscosity, this study suggests that a lower fluidity of the membrane may be responsible for the observed decreases in ATPase activities in the cirrhotic group. Additionally, the role of silymarin to improve liver function in CCl4-cirrhosis can be attributed partially to its action at membrane level by preventing the increases in CH/PL and SM/PC ratios.     

Aspects of cholesterol metabolism in normal and hypercholesterolemic Syrian hamsters. Influence of fenofibrate

This study reports the short-term effects of fenofibrate in golden Syrian hamsters receiving a standard or cholesterol enriched (0.5%) diet. In chow fed control animals, the plasma cholesterol (132 mg/dl) was transported essentially by LDL (27%) and HDL (56%). Conversely, the bulk of triglycerides (114 mg/dl) circulated in VLDL (54%). One week of hypercholesterolemic diet increased plasma cholesterol (+80%) and it is reflected in a 3.3-fold increase in VLDL, 2.8-fold in IDL, 1.6-fold in LDL and 1.5-fold in HDL, accompanied by a rise in cholesterol hepatic level by a factor of 4.5. 15 days of treatment with fenofibrate (300 mg/kg/d) produced a decrease in free plasma cholesterol (-21%) without modification in total cholesterol level in chow fed animals. In liver, cholesterol was reduced by 27% and triglycerides were raised by 58%. In animals receiving the hypercholesterolemic diet, fenofibrate increased hepatic and plasmatic triglyceride levels (55 and 54%, respectively), although it slightly reduced plasma cholesterol levels and more markedly the hepatic cholesterol content (-55%). In chow fed animals, cholesterol biosynthesis was decreased by fenofibrate treatment by 40%. The effects of fenofibrate on triglyceride levels are in contrast to experiences in other animal species, including man, and indicate a hypersecretion of chylomicrons and/or a hypersecretion of VLDL, although the explanations are not yet obvious. The results concerning cholesterol metabolism indicate similarities between man and hamster.     

Effect of selenium on serum, hepatic and lipoprotein lipids concentration in rats fed on a high-cholesterol diet

The effects of Selenium (Se) on lipid metabolism was studied in male Wistar rats which were fed a high-cholesterol diet (HCD) containing 1%(w/w) cholesterol and 0.5%(w/w) cholic acid for 10 weeks. Se was orally administered at daily doses of 0.173 mg/kg in HCD into the test rats for 10 weeks. As compared with control groups, Se/HCD suppressed the amounts of triglyceride (TG), total cholesterol (CH) and free fatty acid in the serum. Se/HCD also decreased the amounts of low-density lipoprotein cholesterol (LDL-C) in the serum. Further-more, Se/HCD inhibited the amount of liver TG and CH. The activity of fatty acid synthetase in the HCD fed group was higher than in the Se/HCD fed group. These results suggest that Se may have recuperative effects for hypercholesterolemia.     

Strains and species differences in experimental hyperlipidemia

Experimental hyperlipidemia was induced in ddY, C57BL, BALB and ICR strain mice and in Wistar rats. By feeding the animals a high cholesterol diet (HCD) for 2 weeks or by administering a high fat emulsion for a week, plasma level of total cholesterol (TC) increased in these animals. The increment of TC in mice was less than that of TC in rats. In rats, plasma level of triglyceride (TG) increased, but it decreased in mice of all these strains. Plasma level of high density lipoprotein cholesterol (HDL-C) decreased in rats and mice except BALB mice. By feeding these animals a HCD, the relative liver weight increased in rats and mice. In rats, clofibrate (CF), 100 mg/kg/day, decreased TC and TG and increased HDL-C, and nicotinic acid (NA), 100 mg/kg/day, decreased and increased HDL-C. However, in mice, CF decreased TC only in ICR mice fed a HCD. The hypolipidemic effects of gemfibrozil, LK-903 and pirozadil were also studied in rats and ICR mice.     

Streptozotocin-induced diabetes in rat. II. Lipid and lipid peroxide changes of lipoprotein fractions in diabetes complicated by hypertension and myocardial infarction

Lipid peroxide levels and plasma lipids were studied in plasma lipoprotein fractions of streptozotocin diabetic rats, spontaneous hypertensive rats (SHR) + diabetes, and in myocardial infarction rats (MIR) + diabetes. The duration of diabetes in all experimental groups was 2.5 months. We found a tendency of elevation of cholesterol in VLDL and fall in HDL2 but the differences were not significant. Total plasma triglycerides were increased in the three diabetic groups, and the increase was due to LDL fraction but again the differences were not significant. The lipid peroxide (LP) level in total plasma showed a significant increase in the three diabetic groups: in Wistar diabetic rats LP increased 3 times, in MIR + diabetes 3.5 times, and in SHR + diabetes 5 times. The increase of LP in the three diabetic groups was due to LDL with good correlation (r = 0.60) between LP and triglycerides in LDL of the three diabetic groups. The results are in agreement with the concept of the importance of lipoprotein fraction changes: increased cholesterol, triglycerides and lipid peroxides in atherogenic (VLDL and LDL) fractions, and decreased levels in antiatherogenic (HDL, HDL2) fractions in diabetes mellitus.     

Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet

1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke-prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol-free diet. 2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven-week-old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water. 3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions. 4. Serum concentrations of apolipoproteins A-I and E (apoA-I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA-IV between the two groups. 5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7alpha-hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl-coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group. 6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA-I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol-free diet.     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

Effect of conjugated linoleic acid (CLA) on lipid profile and liver histology in laboratory rats fed high-fructose diet

The objective of the study was to assess the effect of CLA on serum lipid profile, plasma malondialdehyde and liver histology in Wistar rats fed high-fructose diet. Eighteen rats were randomly assigned to three experimental groups and fed for the next 21 days. The experimental diets were: I, Control; II, Fructose (63.2% of fructose); and III, CLA+Fructose (1% CLA and 63.2% of fructose). The experimental treatments had no effect on body weight of the rats. The LDL+VLDL cholesterol, TG and liver weight were significantly increased in animals fed Fructose. MDA concentrations were significantly increased in rats fed Fructose diet but CLA+Fructose diet had no effect on this marker. In the same line, the histological examination of the livers showed a series of morphological alterations, notably hepatic steatosis in animals fed high-fructose diet. No signs of the steatosis in rats fed CLA+Fructose diet were observed. In conclusion, CLA in high-fructose diet, decreases serum LDL+VLDL and TG and plasma MDA concentrations as well as liver weight and liver cholesterol, thus opposing the effects of high-fructose diet and showing a potential antiatherogenic effect. Similarly, dietary CLA fed at 1% level (w/w) in high-fructose diet, prevented steatosis observed histologically in livers of rats fed high-fructose diets.     

Differential effects of beclobrate on lipid/lipoprotein distribution in normal and hypercholesterolemic rats

Beclobrate, a new fibric acid derivative, displays remarkable lipid lowering activity in rodents. In order to evaluate changes in the distribution and liver handling of lipoproteins, beclobrate was tested in rats fed on a normal or hypercholesterolemic diet. On the normal diet, beclobrate lowered total plasma cholesterol by 22-33.4% (10-50 mg/kg); the cholesterol reduction occurred mainly in high density lipoproteins (HDL) (by 24-45% with the three tested doses). The metabolic clearance of 125I-labelled beta-very low density lipoproteins (beta-VLDL) injected into these animals almost doubled (0.20 1/h vs. 0.13 1/h in controls) after treatment with 20 mg/kg of beclobrate. In addition, beclobrate administration dramatically increased the activity of the high-affinity receptors for beta-VLDL in isolated liver membranes (Bmax: 208 +/- 17.6 vs. 146 +/- 2.6 ng/mg of protein for controls). On the hypercholesterolemic diet, beclobrate treatment (50 mg/kg) was associated with a 25% reduction in total cholesterol accompanied, however, by a 166% rise in HDL cholesterol. In these animals, the composition of VLDL, typically cholesterol-enriched, became close to normal. The increased HDL was characterized by a remarkable enrichment with particles containing apolipoprotein E (apo E), which is compatible with either an improved peripheral cholesterol removal or an enhanced direct secretion of apo E. The two models offer different opportunities for evaluating the mechanism of action of this new lipid lowering agent. Lipoprotein catabolism and receptor-mediated clearance were characteristically improved in normolipidemic rats whereas major effects on HDL metabolism could be demonstrated in hypercholesterolemic rats.     

Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and lipid metabolism in obese and prediabetic sand rats (Psammomys obesus)

Sand rats develop obesity, insulin-resistance, hyperlipidemia and prediabetes, when given a standard laboratory chow diet. We have used this model to demonstrate the beneficial action of olea europea var. oleaster leaves to regulate unbalanced metabolism. 32 sand rats fed on hypercaloric diet during 7 months, were divided into 3 groups: controls (n=10), treated by plant (n=13) and treated by simvastatin (Zoco); hypocholesterolemic drug. The plant decoction prepared at 10% was given orally at the rate of 1.5 ml/100g during 3 months. Results show that the plant presents a hypocholesterolemic effect (42%) related to decreases in LDL and VLDL cholesterol. In addition, hypoglycemic (16%) and antihyperglycemic (40%) effects were observed accompanied by a 27% decrease in insulin. Chronic treatment with Zocor reduced total cholesterol (32%), LDL and VLDL cholesterol. Both of treatments produced no significantly reduction in plasma levels of triglycerides and HDL cholesterol. No noxions effect of this plant have been observed in usual doses.     

Lipid metabolism in liver of rat exposed to cadmium.

We investigated the effect of exposition to cadmium (Cd, 15ppm for 8 weeks) through drinking water on liver lipid metabolism in adult male Wistar rats. As compared to metal non-exposed (control) rats, the serum triglycerides, cholesterol and LDL+VLDL cholesterol concentrations increased. This was associated to a decrease of lipoprotein lipase activity in post heparinic plasma. The VLDL secretion from liver was not modified. Cd treatment increased triglycerides and decreased esterified cholesterol contents in liver. The high triglyceride mass was related to the increased glycerol-3-phosphate acyltransferase mRNA expression. In addition, the liver fatty acids synthesis increased, as determined by an increment of fatty acid synthetase and isocitrate dehydrogenase activities, and [(14)C]-acetate incorporation into saponifiable lipid fraction. The relative percentage of palmitic acid (16:0) and total saturated fatty acids were increased compared with control. Hepatic glucose-6-phosphate dehydrogenase, malic dehydrogenase and cholesteryl ester hydrolase activities were unchanged. In liver, the Cd treatment decreased triglyceride and cholesterol in mitochondria, also increased triglyceride in cytosol, and cholesterol and phospholipid contents in nuclei, compared with control. In addition, an increase of nuclei phosphatidylcholine synthesis was observed. Cd exposure alters directly or indirectly the serum lipid content and liver lipid metabolism.