Search results for "fibrate"
showing 10 items of 84 documents
Induction of the peroxisome proliferator activated receptor by fenofibrate in rat liver
1992
AbstractThe process of peroxisome proliferation in rodent liver by hypolipidemic compounds and related substances has recently been shown to be receptor-madiated. In the present study, we have examined the effect of oral administration of the strong peroxisome proliferator fenofibrate on the hepatic expression level of the peroxisome proliferator activated receptor (PPAR) in rats. Immunoblots of rat liver cytosols and nuclear extracs using antibodies raised against recombinant PPAR/β-galactosidase fusion proteins revealed a pronounced increase in the amount of PPAR protein in response to fenofibrate treatment. This induction could also be confirmed at the level or RNA by Northern blotting. …
IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics.
2010
The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation dat…
Sensitivity of liver metabolism in jerboa (Jaculus orientalis) to ciprofibrate, a peroxisome proliferator.
2009
International audience; Ciprofibrate is a well-known drug used to normalize lipid parameters and fibrinogen in atherosclerosis patients. In laboratory rodents such as rats or mice, ciprofibrate exhibits peroxisome proliferator activity. However, to date, no clear alterations or side effects caused by ciprofibrate have been noted in humans. In order to further investigate such possible relationships, we studied the effects of sustained ciprofibrate treatment in jerboas (Jaculus orientalis). In these rodents, ciprofibrate does not induce hepatomegaly or promote liver cell DNA replication, confirming that this species more closely resembles humans than do rats or mice. The jerboas were treated…
Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2)
2001
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced beta-oxidation of very-long-chain fatty acids), pharmacological induction of these partially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide e…
Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology
1996
Abstract This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The resul…
Time-dependence and differential induction of rat and guinea pig peroxisomal beta-oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxid…
1988
Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01% (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time-dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomal beta-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (le…
Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study.
2007
Objective— Apolipoprotein A5 ( APOA5 ) is a key determinant of plasma triglyceride (TG) concentrations. Genetic variation at the APOA5 locus could be responsible for some of the observed differences in response to fenofibrate therapy. Methods and Results— We examined the association between tag SNPs (−1131T>C and 56C>G) at APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge in 791 men and women participating in the GOLDN study. After 3-week drug treatment, APOA5 56G carriers displayed significant decrease in TG ( P =0.006), and increase in HDL-C ( P =0.002) levels relative to their basal values in the fasting state when compared with noncarriers (a TG re…
Hypolipidaemic effects of fenofibrate and fasting in the herbivorous grass carp (Ctenopharyngodon idella) fed a high-fat diet
2008
We investigated whether the hypolipidaemic effect of fenofibrate and fasting observed in most omnivorous mammals may also apply to herbivorous fish. Grass carp (Ctenopharyngodon idella) fed a high-fat (8 %) diet exhibited a marked increase in blood lipids and body fat after 6 weeks. They were then treated with fenofibrate (100 mg/kg body weight) in the same high-fat diet for 2 weeks, followed by fasting for 1 week. Plasma lipid concentration, body fat amount, fatty acid composition, plasma thiobarbituric acid-reactive substances and some parameters related to hepatic fatty acid oxidation were measured, and liver samples were stained for histological examination. Fenofibrate treatment decrea…
Peroxisome proliferator-activated receptor α (PPARα) activators induce hepatic farnesyl diphosphate synthase gene expression in rodents
2004
Fibrates are hypolipidemic drugs that exert multiple effects on lipid metabolism by activating peroxisome proliferator-activated receptor alpha (PPARalpha) and modulating the expression of many target genes. In order to investigate the link between PPARalpha and cholesterol synthesis, we analysed the effect of fibrates on expression of the farnesyl diphosphate synthase (FPP synthase) gene, known to be regulated by sterol regulatory element-binding proteins (SREBPs), in conjunction with HMG-CoA reductase. In wild-type mice, both fenofibrate and WY 14,643 induced FPP synthase gene expression, an effect impaired in PPARalpha-null mice. A three-fold induction was observed in ciprofibrate-treate…
Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects
2019
Abstract There is no doubt about the relationship between LDL-C and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-C has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterised by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-C and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining …