Drugs online research references
Br J Pharmacol. 1994 Jun;112(2):551-6.
Relationship between plasma lipids and palmitoyl-CoA hydrolase and synthetase activities with peroxisomal proliferation in rats treated with fibrates.
Alegret M, Ferrando R, Vazquez M, Adzet T, Merlos M, Laguna JC.
Dept. Farmacologia y Quimica Terapeutica, Facultad de Farmacia, Nucleo Universitario de Pedralbes, Barcelona, Spain.
1. The time-course of the effect of clofibrate (CFB), bezafibrate (BFB) and gemfibrozil (GFB) on lipid plasma levels and palmitoyl-CoA hydrolase and synthetase activities, as well as the correlations with the peroxisomal proliferation phenomenon have been studied in male Sprague-Dawley rats. 2. The administration of the three drugs caused a significant reduction in body weight gain, accompanied with a paradoxical increase in food intake in groups treated with BFB and GFB. 3. Drug treatment produced gross hepatomegaly and increase in peroxisomal beta-oxidation, and these parameters were strongly correlated. The order of potency was BFB > CFB > or = GFB. 4. Both plasma cholesterol (BFB approximately CFB > GFB) and triglyceride (BFB approximately GFB > CFB) levels were reduced in treated animals. There was an inverse correlation between these parameters and peroxisomal beta-oxidation, although the peroxisomal proliferation seemed to explain only a small part of the hypolipidemic effect observed. 5. Cytosolic and microsomal (but not mitochondrial) palmitoyl-CoA hydrolase activities were increased by the three drugs (BFB > CFB > GFB), probably by inducing the hydrolase I isoform, which is insensitive to inhibition by fibrates in vitro. The increased hydrolase activities were directly and strongly correlated with peroxisomal beta-oxidation. 6. Palmitoyl-CoA synthetase activity was also increased by the treatment with fibrates (BFB > CFB > GFB), probably as a consequence of the enhancement of hydrolase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7915611&dopt=Abstract
Eur J Clin Invest. 1985 Apr;15(2):100-12.
Plasma apolipoprotein B metabolism in familial type III dysbetalipoproteinaemia.
Turner PR, Cortese C, Wootton R, Marenah C, Miller NE, Lewis B.
Lipoprotein metabolism was studied in eleven patients with Type III hyperlipoproteinaemia, one with normolipidaemic dysbetalipoproteinaemia and eight controls. Apolipoprotein B kinetics in very low density, intermediate density and low density lipoproteins (VLDL, IDL and LDL) was investigated. Fractional catabolic rates (FCRs) of VLDL-apo B and IDL-apo B were lower (P less than 0.005 and P less than 0.001) in the patients: 0.064 +/- 0.018 and 0.059 +/- 0.006 h-1 respectively, (mean +/- SEM), compared with 0.219 +/- 0.035 and 0.243 +/- 0.028 h-1. Synthetic rates (SRs) of IDL-apo B varied widely from 1.5 mg kg-1 day-1 in the subject with normolipidaemic dysbetalipoproteinaemia to 2.8-25.2 mg kg-1 day-1 in Type III. The mean time for conversion of IDL-apo B to LDL-apo B was prolonged, 18.7 h compared with 3.8 h in the controls (P less than 0.001). LDL-apo B pool size and SR were lower in the patients (P less than 0.05 for both). Two patients treated with gemfibrozil showed reduced hyperlipidaemia and decreased SR of VLDL-apo B and IDL-apo B. Dysbetalipoproteinaemia is associated with pronounced impairment of IDL and VLDL-remnant catabolism, lipoprotein levels reflecting an interaction between this defect and SR of these lipoproteins.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3922766&dopt=Abstract
FEBS Lett. 1992 Mar 23;300(1):89-92.
Inhibition of rat liver microsomal fatty acid chain elongation by gemfibrozil in vitro.
Sanchez RM, Vinals M, Alegret M, Vazquez M, Adzet T, Merlos M, Laguna JC.
Dept. Farmacologia y Quimica Terapeutica, Facultad de Farmacia, Barcelona, Spain.
Gemfibrozil, a hypolipidemic drug mainly used in the treatment of hypertriglyceridemic states, strongly inhibits the rat hepatic microsomal fatty acid chain elongation system in vitro. The inhibition is independent on the reducing cofactor used in the assay. Furthermore, gemfibrozil seems to act by inhibiting the rate-limiting step of the elongation process, the condensing reaction, without discriminating among the proposed three different condensing enzymes, devoted to condensation of saturated, mono-unsaturated and polyunsaturated acyl-CoA substrates.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1547894&dopt=Abstract
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