Search results for "Clofibrate"
showing 10 items of 12 documents
Expression of Putative Fatty Acid Transporter Genes Are Regulated by Peroxisome Proliferator-activated Receptor α and γ Activators in a Tissue- and I…
1998
Regulation of gene expression of three putative long-chain fatty acid transport proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase (mAspAT), and fatty acid transport protein (FATP), by drugs that activate peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver and intestine of normal mice and in hepatoma cells to various extents only by PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a lesser extent in intestine. The induction time course in the liver was slower for FAT and FATP mRNA than that of an mRNA encoding a peroxisomal en…
Lipid-lowering drug use in Italian primary care: effects of reimbursement criteria revision
2008
OBJECTIVE: To assess whether the prescribing pattern of lipid-lowering drugs (LLD) changed after reimbursement criteria revision in a general practice in southern Italy. METHODS: From the Caserta-1 Local Health Service database, 93 general practitioners (GPs) who had consistently sent data about their patients during the years 2003-2005 were recruited. Prevalence of use and incidence of new treatments were calculated for each year, stratified by three drug cohorts: statins, omega-3 fatty acids, and fibrates. Subanalyses by gender, age, and indication of use were performed. RESULTS: Overall, 1-year prevalence of LLD use increased from 2003 to 2004. After reimbursement criteria revision (Nove…
Differential subcellular localization of endogenous and transfected soluble epoxide hydrolase in mammalian cells: evidence for isozyme variants
1999
AbstractEndogenous, constitutive soluble epoxide hydrolase in mice 3T3 cells was localized via immunofluorescence microscopy exclusively in peroxisomes, whereas transiently expressed mouse soluble epoxide hydrolase (from clofibrate-treated liver) accumulated only in the cytosol of 3T3 and HeLa cells. When the C-terminal Ile of mouse soluble epoxide hydrolase was mutated to generate a prototypic putative type 1 PTS (-SKI to -SKL), the enzyme targeted to peroxisomes. The possibility that soluble epoxide hydrolase-SKI was sorted slowly to peroxiosmes from the cytosol was examined by stably expressing rat soluble epoxide hydrolase-SKI appended to the green fluorescent protein. Green fluorescent…
Rat Cytosolic Epoxide Hydrolase
1986
Rat liver microsomal and cytosolic epoxide hydrolase may be distinguished through differences in substrate specificity: styrene 7,8-oxide is preferentially hydrolyzed by the microsomal form, while trans-stilbene oxide is the prefered substrate for cytosolic epoxide hydrolase. Large interindividual differences in the specific activity of SpragueDawley (outbred strain) liver cytosolic epoxide hydrolase were observed, varying from 2 to 77 pmol/min x mg protein. Interindividual variations were much lower for microsomal epoxide hydrolase. The specific activity of Fischer F-344 (inbred strain) liver cytosolic epoxide hydrolase varied only by a factor of 2. The specific activity of cytosolic epoxi…
Elongation and desaturation of arachidonic and eicosapentaenoic acids in rat liver. Effect of clofibrate feeding
1991
The fatty acid elongation-desaturation ability of 5,8,11,14-eicosatetraenoic (20:4(n-6)) and 5,8,11,14,17-eicosapentaenoic (20:5(n-3)) acids was determined in both liver microsomal and light mitochondrial (rich in peroxisomes) fractions of untreated and clofibrate treated rats. The elongation and the subsequent desaturation steps were performed in the corresponding favorable media. 20:5(n-3) elongation was about 2-times more extensive than that of 20:4(n-6). Clofibrate feeding for 10 days resulted in a marked decrease in the elongation rate with the two substrates, while the delta 4 desaturation rate was increased. There were small differences in the elongation rate between the microsomal a…
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…
Expression of liver peroxisomal proteins as compared to other organelle marker enzymes in rats treated with hypolipidemic agents.
1990
Abstract Peroxisome proliferation induced by 2 hypolipidemic agents (clofibrate and ciprofibrate) was studied in rats by complementary approaches, ie cell fractionation, electron microscopy, marker enzyme activities, immunoblotting and nucleic acid hybridization techniques. Administration of clofibrates for 2 and 52 weeks in doses of 500 ppm and 50 ppm respectively, or ciprofibrate for 2,28 and 52 weeks in doses of 250, 25 and 25 ppm respectively, did not alter the behavior of the peroxisomes after induction as shown by ultracentrifugation profiles. The peroxisome mass was increased as shown by the purification procedure. Specific enzymes (catalase and mostly cyanide insensitive palmitoyl C…
Differential proto-oncogene mRNA induction from rats treated with peroxisome proliferators
1990
After experimental treatment of rats with clofibrate or ciprofibrate, two peroxisomes proliferators with hypolipidemic activity, RNAs were prepared from liver, kidney, heart and brain; hybridization was done with DNA probes for c-myc and c-Ha-ras oncogenes and for cyanide insensitive Acyl CoA oxidase, a peroxisomal protein. c-myc mRNA is highly abundant in liver and at a lower extent in kidney, especially after treatment with ciprofibrate; clofibrate also allows a c-myc mRNA increase, but at a lower extent. c-Ha-ras, which is already expressed in all tested tissues from control animals, is stimulated by clofibrate and ciprofibrate treatments. Comparatively these compounds stimulate the cyan…
Mitochondrial myopathy--a result of clofibrate/etofibrate treatment? Case report.
1985
A 66-year-old man had developed a myopathy while undergoing several periods of etofibrate and clofibrate therapy over the past 5 years. Discontinuation of etofibrate treatment failed to reverse his muscle illness which, however, did not progress. A muscle biopsy revealed a chronic myopathy marked by abundant, abnormally structured muscle mitochondria. His mitochondrial myopathy may represent a forme fruste of the Kearns-Sayre syndrome or other types of mitochondrial myopathy, clinically made evident by the etofibrate/clofibrate therapy, or a permanent, adverse side effect of clofibrate treatment. If the latter assumption proves to be correct, it will indicate that clofibrate therapy may ind…
Cholesterol-Like Effects of Selective Cyclooxygenase Inhibitors and Fibrates on Cellular Membranes and Amyloid-β Production
2007
Strong evidence suggests a mechanistic link between cholesterol metabolism and the formation of amyloid-beta peptides, the principal constituents of senile plaques found in the brains of patients with Alzheimer's disease. Here, we show that several fibrates and diaryl heterocycle cyclooxygenase inhibitors, among them the commonly used drugs fenofibrate and celecoxib, exhibit effects similar to those of cholesterol on cellular membranes and amyloid precursor protein (APP) processing. These drugs have the same effects on membrane rigidity as cholesterol, monitored here by an increase in fluorescence anisotropy. The effect of the drugs on cellular membranes was also reflected in the inhibitory…