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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antilipidemic properties of certain benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a hyperlipidemic rat model are described. The hyperlipidemia was induced by intraperitoneal injection of Triton WR-1339. The results were analyzed in light of structural modifications as well as the lipid solubility of substituted compounds as assessed by a consideration of calculated log P values. Comparisons are made between the activity of these compounds and the activity of related cyclic analogs previously reported. Among the various compounds tested, only the 5-C1 and phenylsybstituted dihydrobenzofurans were selective against elevated serum cholesterol levels in this animal model. The data presented support the hypothesis that the cholesterol and triglyceride lowering activity of clofibrate related analogs in this animal model may be separated through a consideration of log P, conformational, and electronic changes. The proposal is advanced that relatively minor structural modification of clofibrate related analogs may lead to compounds which are not only selective in the Triton model but also to compounds which are likely to exert their effects by differing modes of action.
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PMID:Comparative antilipidemic effects of various ethyl 5-substituted benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a triton hyperlipidemic rat model. 127 76

In an attempt to elucidate the role of the dietary fermentable fiber in reduction of hyperlipidemia, we substituted 30% wheat starch with 30% sugar-beet fiber in rats fed a fructose-based (41% fructose), low-fat (2% corn oil) diet. Male Wistar rats ate the test diets for 3 weeks. Feeding the sugar-beet fiber (SBF) diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids compared with rats fed a fiber-free (FF) diet. Feeding SBF decreased plasma triglyceride and cholesterol concentrations in the postprandial as well as the postabsorptive period. In the liver, triglyceride levels were depressed in concert with the decreased liver lipogenesis and the post-Triton triglyceride secretion. Liver cholesterol levels were unaffected by SBF diet feeding. SBF-fed animals were markedly less fat compared with fiber-free-diet-fed rats. Adipose tissue lipogenesis was depressed in the postprandial period in SBF-fed animals. In short, this study suggests that substitution of easily digested carbohydrates by certain fermentable fibers may play an interesting role in the reduction of hyperlipidemia and obesity.
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PMID:Effects of dietary fermentable fiber on fatty acid synthesis and triglyceride secretion in rats fed fructose-based diet: studies with sugar-beet fiber. 131 52

The JCR:LA-corpulent rat is an obese, hyperlipidemic, hyperinsulinemic strain that is atherosclerosis-prone and develops myocardial lesions. The hyperlipidemia is due to elevated plasma levels of a large relatively triglyceride-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparin lipid clearance and apparent hepatic secretion rate after Triton WR1339 inhibition of lipoprotein lipase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment. Triglycerides showed rapid postheparin clearance in corpulent rats. The apparent hepatic secretion rate was markedly higher in corpulent male rats than in lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum triglyceride concentrations in corpulent female rats. The relative secretion rate of C:48 triglyceride molecular species was lower than that of the C:50 to C:56 species, while the postheparin clearance of C:48 triglyceride molecular species was impaired compared to the C:50 species and those with higher carbon numbers. This effect was more marked in the male than in the female corpulent rats. The results indicate that VLDL hyperlipidemia in the corpulent rat is due to hepatic hypersecretion of VLDL and not to a defect in lipoprotein lipase. Further, the atherogenesis that is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids.
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PMID:Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats. 259 65

The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.) for 8 days. Ciprofibrate is about 25-fold more active than fenofibrate in reducing plasma triglyceride and cholesterol concentrations both in normolipemic and in hyperlipemic rats. In normolipemic rats ciprofibrate reduced the concentration and the lipid content of all lipoprotein classes. The incorporation of [14C]palmitate and [3H]leucine into the lipoproteins was reduced by ciprofibrate and fenofibrate. The reduction in lipoprotein production was confirmed by prevention of Triton-induced hyperlipemia. Liver and plasma cholesterol synthesis estimated by 3H2O and [14C]mevalonate incorporation indicated an inhibitory effect on HMG-CoA reductase. Administration of ciprofibrate or fenofibrate to rats fed a fat and cholesterol-rich diet partially prevented liver steatosis and hyperlipemia. Both drugs reduced the overproduction of lower density lipoproteins. The ratio of (VLDL + LDL)-cholesterol/HDL-cholesterol which was increased by the diet alone from 0.4 (normal) to 11 remained close to the normal value in the animals receiving ciprofibrate. In the hyperlipemic animals, ciprofibrate reduced the incorporation of [3H]oleate into the liver and plasma glycerolipid and increased cholesterol esterification. Ciprofibrate efficiently reduces plasma levels of cholesterol, triglyceride and phospholipid. Cholesterol and glycerolipid synthesis in the liver were significantly reduced leading to a lower lipoprotein secretion rate in both normolipidemic and diet-induced hyperlipidemic rats.
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PMID:Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. 324 Mar 33

The hypolipidemic activity of tiadenol-disulfoxide, the major metabolite of 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) in man and in the rat was assessed in various experimental models versus the corresponding activity of tiadenol. Tiadenol-disulfoxide in the normolipidemic rats lowers total serum cholesterol and serum and liver triglycerides in an extent comparable to that of the reference compound. Likewise, it is equally effective as tiadenol in preventing Triton-induced hyperlipidemia and Nath diet induced hypercholesterolemia; in addition tiadenol-disulfoxide is slightly more effective than tiadenol in increasing HDL-cholesterol in hypercholesterolemic rats. At hypolipidemic doses the compound causes no hepatomegaly, no induction of peroxisomal catalase and palmitoyl-CoA oxidase activities, no smooth endoplasmic reticulum proliferation and no induction of microsomal cytochrome P-450 and of cytochrome P-450 dependent enzyme activities: aminopyrine (aminophenazone) N-demethylase, aniline hydroxylase, zoxazolamine hydroxylase and hexobarbital oxidase. At the suprapharmacological dose of 300 mg/kg tiadenol-disulfoxide, if compared to the reference compound, shows a generally lower order of toxicity on these hepatic parameters. Orally administered tiadenol-disulfoxide is well absorbed by the gastrointestinal tract and is eliminated in urine at 45% of the dose in unchanged form, and the remaining being: glucuron-conjugated tiadenol-disulfoxide (10%), S-oxidized metabolites (15%) and sulfoxidized carboxylic metabolites (15%). The compound is well tolerated both in mice and rats. The results of this comparative study demonstrate that: 1. tiadenol-disulfoxide is a substance with promising hypolipidemic properties; 2. tiadenol-disulfoxide is largely responsible for the hypolipidemic activity of tiadenol; 3. hepatomegaly consequent to tiadenol administration is the consequence of the response of the liver cell to the increased functional demand of the mixed function oxidase (MFO) system involved in the metabolism of the drug; 4. peroxisomal enzyme activities induction observed with both drugs at non-pharmacological doses does not play any role in their hypolipidemic action and is not associated with hepatomegaly.
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PMID:Experimental studies on pharmacology, metabolism and toxicology with tiadenol-disulfoxide. Dissociation of lipid lowering effects and the induction of peroxisomal and microsomal drug-metabolizing enzymes. 366 66

The hypolipidemic activity of the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) was assessed in various experimental conditions versus the corresponding activities of nicotinyl alcohol (NA), nicotinyl alcohol hemisuccinate (NAH), nicotinic acid (NAC), and pantethine tetranicotinate (PTN). In the normolipidemic rat, MG 28362 causes a more durable reduction of non-esterified fatty acids (NEFA) and serum triglycerides than the reference products. NEFA values return slowly to pretreatment levels without causing the rebound effect typical of most nicotinic acid derivatives. Likewise in the test of ethanol-induced hypertriglyceridemia, MG 28362 shows more pronounced and sustained activity compared to the reference products. It is also more effective on Triton hyperlipidemia and on diet-induced hypercholesterolemia; in the latter test, MG 28362 caused no triglyceride accumulation in the liver. Even at high dosage levels, MG 28362 did not cause the characteristic flushing of nicotinic acid congeners. Last, the new substance displays a fairly marked antiaggregating activity on blood platelets, some anti-hypoxic activity, and a generally low order of toxicity.
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PMID:Pharmacological study of a new hypolipidemic drug of prolonged activity, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid. 384 36

The available preclinical literature on the antihyperlipidemic properties of beta-pyridylcarbinol is reviewed. Similarities between the pharmacological profiles for beta-pyridylcarbinol and nicotinic acid, and evidence for the metabolic conversion of beta-pyridylcarbinol to nicotinic acid are discussed. Several reviews discussing the antihyperlipidemic effects of beta-pyridylcarbinol (beta-PC, nicotinyl alcohol, Roniacol) and nicotinic acid (NA) have appeared during the last 15 years (1-6). However, continuing clinical interest in the ability of nicotinic acid analogs to reduce plasma lipids indicated that an update and critical evaluation of the preclinical literature on this subject would be of value in order to permit a more complete assessment of the relevance of several animal models to effects in human subjects. The literature reviewed included (a) preclinical studies of beta-PC where it was the sole compound examined; (b) comparative studies of beta-PC and NA; and (c) studies relating to the metabolism of beta-PC. The literature chosen included experiments involving fasted animals, satiated animals, and effects of Triton-induced hyperlipidemia. Data on other pharmacological properties of beta-PC and/or NA that might contribute to antihyperlipidemic efficacy (e.g., fibrinolysis, inhibition of platelet aggregation, erythrocyte membrane changes) were also included where available.
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PMID:Antihyperlipidemic properties of beta-pyridylcarbinol. A review of preclinical studies. 390 30

Acrylophenone derivatives with in vitro antimicrotubular activities very similar to those of colchicine were tested on Triton WR 1339-induced hyperlipidemia in rats. They exhibit high normolipemic activity on plasmatic apolipoproteins AI and B, contrasting with inactivity on plasmatic lipids and lipoproteins.
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PMID:Normolipemic activities of acrylophenone derivatives with antimicrotubular properties. 402 50

In rats with hyperlipemia induced by Triton WR-1339, changes in tocopherol concentrations in plasma and RBC were compared with those in the liver and its subcellular fractions, microsomes and mitochondria. After daily injection with Triton, plasma total lipids at 3 days and 7 days, respectively, showed elevations 6.5 times and 15 times as high as those in the control rats, and triglycerides showed the most predominant elevation. With the hyperlipemia, the concentrations of tocopherol in RBC and the subcellular fractions decreased, as plasma lipids and plasma tocopherol increased, while no change occurred in tocopherol concentrations in liver homogenates. The changes in the ratio of tocopherol to total lipids in plasma coincided with changes in tocopherol concentrations in the RBC and subcellular fractions.
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PMID:Red blood cell tocopherol and liver tocopherol in hyperlipemic rats as compared with plasma tocopherol. 403 67

Nine (amino-methyl)-2 acrylophenone derivatives having in vitro antimicrotubular activities very similar to those of colchicine are tested on Triton WR 1339-induced hyperlipidemia in rats. By producing a disorganization of the microtubular system, these drugs reduce the lipoprotein secretory process from hepatocytes, and more particularly the triglyceride-rich VLDL secretory process, such that the serum triglyceride, cholesterol and phospholipid levels are decreased. On the other hand, HDL-cholesterol and HDL-phospholipids are increased in a significant manner. Other studies show that serum apoprotein B levels are decreased while serum apoprotein A1 levels are increased. These results are interesting since atherogenous risk is now known to be dyslipemia-related, and is not the same according to the fact that lipids are bound to one or another lipoprotein. Among the four most effective compounds (5,7,8 and 9) three of them possess a methoxy group on the aromatic ring, which seems to distinguish that series from the other two.
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PMID:Pharmacological study of nine antimicrotubular drugs with acrylophenone structure on Triton WR 1339-induced hyperlipidemia in rats. 408 77


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