Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Red blood cell tocopherol and liver tocopherol in hyperlipemic rats as compared with plasma tocopherol. 403 67

Arginine decreased cholesterol and triglyceride content in blood sera of intact rats and inhibited the development of hyperlipidemia provoked by Triton WR-1339 injection. In rabbits pretreated with cholesterol arginine diminished the content of blood serum cholesterol and triglycerides. Introduction of arginine to intact and hyperlipidemic guinea pigs decreased the VLDL and increased the HDL level. Under influence of arginine electrophoretic zone of HDL apo A-1 was more pronounced and apo E zone became less distinct in hyperlipidemic guinea pigs.
 ...
PMID:[Effect of arginine on the lipid and lipoprotein content of animal blood]. 652 39

L-DOPA, which is a metabolic precursor of catecholamines, reduced the manifestations of hyperlipidemia developed in animals after administration of Triton WR-1339, dexametasone or cholesterol. At the same time, L-DOPA decreased the rate of lipolysis, induced by adrenaline injection, as well as the content of 11-hydrocorticosteroids in blood plasma.
 ...
PMID:[Effect of L-dopa on some patterns of lipid metabolism in experimental animals]. 728 65

Vaccinium myrtillus L. (blueberry) leaf infusions are traditionally used as a folk medicine treatment of diabetes. To further define this therapeutical action, a dried hydroalcoholic extract of the leaf was administered orally to streptozotocin-diabetic rats for 4 days. Plasma glucose levels were consistently found to drop by about 26% at two different stages of diabetes. Unexpectedly, plasma triglyceride (TG) were also decreased by 39% following treatment. Subsequent to the latter observation, possible lipid-lowering properties of the extract were investigated on other models of hyperlipidaemia and ciprofibrate, a well-established hypolipidaemic drug, was used as a reference compound. Both drug reduced TG levels of rats on hyperlipidaemic diet in a dose-dependent fashion. When administered at single doses over the same experimental period, blueberry and ciprofibrate were effective in lowering TG concentrations in ethanol-treated normolipidaemic animals and in genetically hyperlipidaemic Yoshida rats. Unlike ciprofibrate, however, blueberry failed to prevent the rise in plasma TG elicited by fructose and did not affect free fatty acid levels in any of the above experimental conditions. In rats treated with Triton WR-1339, blueberry feeding induced an hypolipidaemic activity one hour after injection but proved to be ineffective at later time points, thus suggesting that its hypolipidaemic action may reflect improved TG-rich lipoprotein catabolism. In addition, ciprofibrate and the extract were tested for antithrombotic activity using a collagen-triggered model of venous thrombosis in diabetic and Yoshida rats. Only ciprofibrate, however, significantly reduced thrombus formation in diabetics, possibly because of its effects on free fatty acid metabolism, whereas no effect was observed in Yoshida rats. In conclusion, the present findings indicate that active consituent(s) of Vaccinium myrtillus L. leaves may prove potentially useful for treatment of dyslipidaemiae associated with impaired TG-rich lipoprotein clearance.
 ...
PMID:Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. 894 58

Hyperlipidemia may complicate the use of HIV protease inhibitors (PIs) in AIDS therapy. To determine the cause of hyperlipidemia, the effect of PIs on lipid metabolism was examined with HepG2 liver cells and AKR/J mice. In HepG2 cells, the PIs ABT-378, nelfinavir, ritonavir, and saquinavir stimulated triglyceride synthesis; ritonavir increased cholesterol synthesis; and amprenavir and indinavir had no effect. Moreover, nelfinavir increased mRNA expression of diacylglycerol acyltransferase and fatty acid synthase. The retinoid X receptor agonist LG100268, but not the antagonist LG100754, further increased PI-stimulated triglyceride synthesis and mRNA expression of fatty acid synthase in vitro. In fed mice, nelfinavir or ritonavir did not affect serum glucose and cholesterol, whereas triglyceride and fatty acids increased 57% to 108%. In fasted mice, ritonavir increased serum glucose by 29%, cholesterol by 40%, and triglyceride by 99%, whereas nelfinavir had no effect, suggesting these PIs have different effects on metabolism. Consistent with the in vitro results, nelfinavir and ritonavir increased triglyceride 2- to 3-fold in fasted mice injected with Triton WR-1339, an inhibitor of triglyceride clearance. We propose that PI-associated hyperlipidemia is due to increased hepatic triglyceride synthesis and suggest that retinoids or meal restriction influences the effects of select PIs on lipid metabolism.
 ...
PMID:HIV protease inhibitors stimulate hepatic triglyceride synthesis. 1111 63

A newly synthesized benzoic acid derivative, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]methoxybenzoic acid (S-2E), has the capacity to inhibit the biosynthesis of both sterol and fatty acids. Here, we report the mechanism by which S-2E lowers blood cholesterol and triglyceride levels. In the liver, S-2E was converted into its active metabolite, S-2E-CoA. S-2E-CoA noncompetitively inhibited the enzymatic activities of both 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and acetyl-CoA carboxylase at K(i)=18.11 microM and K(i)=69.2 microM, respectively. Interestingly, pharmacokinetic experiments in rats showed that the concentration of S-2E-CoA in the liver was sufficient to inhibit the activities of HMG-CoA reductase and acetyl-CoA carboxylase, for example, when orally given to rats at 10 mg/kg. Indeed, S-2E (3-30 mg/kg) given orally suppressed the secretion rate of very-low-density lipoprotein (VLDL)-cholesterol and triglyceride in Triton WR-1339-injected rats. Furthermore, S-2E lowered the blood total cholesterol and triglyceride levels simultaneously in Zucker fatty rats. Collectively, S-2E may be useful in the treatment of familial hypercholesterolemia and mixed hyperlipidemia.
 ...
PMID:Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative, S-2E. 1280 54

A microsomal triglyceride transfer protein (MTP) inhibitor, CP-346086, was identified that inhibited both human and rodent MTP activity [concentration giving half-maximal inhibition (IC50) 2.0 nM]. In Hep-G2 cells, CP-346086 inhibited apolipoprotein B (apoB) and triglyceride secretion (IC50 2.6 nM) without affecting apoA-I secretion or lipid synthesis. When administered orally to rats or mice, CP-346086 lowered plasma triglycerides [dose giving 30% triglyceride lowering (ED30) 1.3 mg/kg] 2 h after a single dose. Coadministration with Tyloxapol demonstrated that triglyceride lowering was due to inhibition of hepatic and intestinal triglyceride secretion. A 2 week treatment with CP-346086 lowered total, VLDL, and LDL cholesterol and triglycerides dose dependently with 23%, 33%, 75%, and 62% reductions at 10 mg/kg/day. In these animals, MTP inhibition resulted in increased liver and intestinal triglycerides when CP-346086 was administered with food. When dosed away from meals, however, only hepatic triglycerides were increased. When administered as a single oral dose to healthy human volunteers, CP-346086 reduced plasma triglycerides and VLDL cholesterol dose dependently with ED50s of 10 mg and 3 mg, and maximal inhibition (100 mg) of 66% and 87% when measured 4 h after treatment. After a 2 week treatment (30 mg/day), CP-346086 reduced total and LDL cholesterol and triglycerides by 47%, 72%, and 75%, relative to either individual baselines or placebo, with little change in HDL cholesterol. Together, these data support further evaluation of CP-346086 in hyperlipidemia.
 ...
PMID:CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. 1283 54

Triton WR-1339, a non-ionic detergent, added to canine serum or to ultracentrifugally separated lipoproteins, induced changes in the lipoproteins which were dependent upon concentration of detergent and class of lipoproteins. D 1.063 to 1.21 lipoprotein (alpha-LP) was especially sensitive to the action of triton. Addition of 2 mg. of triton to 1 mg. of alpha-LP (based on protein content), induced only slight changes in the electrophoretic and flotation characteristics of the lipoprotein. With a tenfold increase of the detergent (triton:alpha-LP, 20:1), the mixture, analyzed by starch gel and paper electrophoresis, yielded a tritonlipid complex which remained close to the origin, and a nearly lipid-free protein with electrophoretic mobility higher (starch gel) or lower (paper) than native alpha-LP. The splitting of the lipid and protein moieties of alpha-LP could not be clearly shown when the same mixture was analyzed by free boundary electrophoresis. Triton alone moved only slightly in an electrical field (paper, starch gel, Tiselius); it sedimented during ultracentrifugation at D 1.006 and D 1.063 and floated at D 1.21. D 1.006 to 1.063 lipoproteins (beta-LP), required larger amounts of triton to show changes. These were evident in 40 to 80:1 mixtures of triton and beta-LP. In starch gel and paper electrophoresis triton retained, in a position close to the origin, part of the lipids of beta-LP; the remaining beta-LP fraction, impoverished of lipids, had electrophoretic mobility similar to native beta-LP. The triton-lipid complex sedimented at D 1.063. After addition of triton to complexes [chylomicron-alpha-P-I(131)] or [lipomul-alpha-LP-1(131)], the electrophoretic and ultracentrifugal analyses of these mixtures revealed that the labeled protein was removed from the triglyceride component. Triton also prevented the occurrence of the interaction between lipomul and alpha-LP and the hydrolysis of both chylomicrons and lipomul-alpha-LP by lipoprotein lipase. It is postulated that, if the changes in lipoproteins and chylomicrons observed in vitro occur in vivo, they could account, at least in part, for the hyperlipemia which develops in animals following administration of triton.
 ...
PMID:Triton hyperlipemia in dogs. I. In vitro effects of the detergent on serum lipoproteins and chylomcrons. 1374 54

The pancreatic lipase inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum TG level in corn oil feeding-induced triglyceridemic mice, as well as that of serum triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
 ...
PMID:Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite Crocetin. 1627 98

Tyloxapol (Triton WR 1339) is a non-ionic detergent that inhibits lipoprotein lipase and thereby raises levels of serum lipids. It is used frequently for acute studies on lipids in rats but not for subacute or chronic studies. In the present work, we found that tyloxapol must be injected intravenously three times each week in order to have high and sustained levels of serum cholesterol and triglycerides for 1, 2, or 3 weeks. These results make it possible to extend the use of tyloxapol into chronic studies of hyperlipemia and vascular disease.
 ...
PMID:A procedure for inducing sustained hyperlipemia in rats by administration of a surfactant. 1683 86


<< Previous 1 2 3 4 5 6 7 Next >>