Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of bezafibrate on hepatic peroxisome-associated enzymes of rats, mice, guinea pigs, hamsters, rabbits, dogs and monkeys were examined. Dogs and monkeys were given bezafibrate orally at 30 mg/kg body wt daily for 2 weeks and at 125 mg/kg body wt daily for 13 weeks, respectively, and other species at 100 mg/kg daily for 2 weeks. In male rats, marked changes were observed in the activities of catalase (1.73-fold), D-amino acid oxidase (DAAO; 0.56-fold), fatty acyl-CoA oxidizing system (FAOS; 12.9-fold) and carnitine acetyltransferase (CAT; 35.8-fold); in female rats, the changes were less than in the males. In mice, there were no apparent sex differences in the responses of hepatic peroxisomal enzymes to bezafibrate and the increases in the activities of catalase, FAOS and CAT were 1.76-, 3.75- and 7.94-fold respectively. In guinea pigs, only slight increases in the activities of FAOS (3.00-fold) and CAT (2.83-fold) were observed. In hamsters, the increases in catalase, FAOS and CAT activities, were 1.23-, 2.19- and 2.77-fold respectively. Although rabbits and dogs showed slight increases in CAT activity, no significant response to the drug was observed in monkeys. Hepatomegaly and the increase of hepatic content of peroxisome proliferation-associated polypeptide (PPA-80), which has been recognized as a peroxisomal bifunctional protein in the fatty acid beta-oxidation pathway, were observed only in rats and mice. These results show that there were marked species differences in the effects of bezafibrate on hepatic peroxisomes, and that bezafibrate induced hepatic peroxisome proliferation in rodents, especially rats and mice.
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PMID:Species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes. 291 22

The hypolipidaemic agents ciprofibrate and Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid) and the phthalate-ester plasticizer di-(2-ethylhexyl)-phthalate (DEHP), like other peroxisome proliferators, produce a significant hepatomegaly and induce the peroxisomal fatty acid beta-oxidation enzyme system together with profound proliferation of peroxisomes in hepatic parenchymal cells. Changes in the profile of liver proteins in rats following induction of peroxisome proliferation by ciprofibrate, Wy-14,643 and DEHP have been analysed by high-resolution two-dimensional gel electrophoresis. The proteins of whole liver homogenates from normal and peroxisome-proliferator-treated rats were separated by two-dimensional gel electrophoresis using isoelectric focusing for acidic proteins and nonequilibrium pH gradient electrophoresis for basic proteins. In the whole liver homogenates, the quantities of six proteins in acidic gels and six proteins in the basic gels increased following induction of peroxisome proliferation. Peroxisome proliferator administration caused a repression of three acidic proteins in the liver homogenates. By the immunoblot method using polyspecific antiserum against soluble peroxisomal proteins and monospecific antiserum against peroxisome proliferation associated Mr 80000 polypeptide (polypeptide PPA-80), the majority of basic proteins induced by these peroxisome proliferators appeared to be peroxisomal proteins. Polypeptide PPA-80 becomes the most abundant protein in the total liver homogenates of peroxisome-proliferator-treated rats. These results indicate that ciprofibrate, DEHP and Wy-14,643 induce marked changes in the profile of specific hepatic proteins and that some of these changes should serve as a baseline to identify a set of gene products that may assist in defining the specific 'peroxisome proliferator domain'.
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PMID:Specific changes in the protein composition of rat liver in response to the peroxisome proliferators ciprofibrate, Wy-14,643 and di-(2-ethylhexyl)phthalate. 400 98

There is a considerable interest in developing potent and safe hypolipidemic drugs for the prevention and management of coronary heart disease in man. In rodents, many of these hypolipidemic compounds induce hepatomegaly, proliferation of peroxisomes and a polypeptide with an approximate mol. wt. of 80000 in liver cells. In the present study, we have examined 10 hypolipidemic compounds for the induction of peroxisome proliferation associated 80000 mol. wt. polypeptide (polypeptide PPA-80), peroxisomal enzymes and peroxisome proliferation in rat liver, in view of the emerging evidence that hepatic peroxisome proliferators as a class are carcinogenic in rats and mice. All ten compounds, fenofibrate (isopropyl-[4-(p-chlorobenzoyl)2-phenoxy-2-methyl] propionate; LS 2265 (taurine derivative of fenofibrate); bezafibrate (2-(4-(2-[4-chlorobenzamido)ethyl] phenoxy)-methyl propionic acid; gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid); methyl clofenapate (methyl-2-[4-(p-chlorophenyl)phenoxy]-2-methyl propionate); DG 5685 (5-[4-phenoxybenzyl]trans-2-(3-pyridyl)1,3-dioxane); DH 6463 (5-[4-phenoxybenzyl] trans-2-(3-pyrimidinyl)-1,3-dioxane); tiadenol(bis[hydroxyethylthio]-7, 10-decane); ciprofibrate (2,-[4-(2,2-dichlorocyclopropyl)-phenoxy]2-methyl propionic acid) and RMI-14,514 ( [5-tetradecycloxy]-2-furancarboxylic acid), produced a marked but variable increase in the activities of peroxisomal enzymes catalase, carnitine acetyltransferase, heat-labile enoyl-CoA hydratase and the fatty acid beta-oxidation system and in the amount of polypeptide PPA-80 as demonstrated by SDS-polyacrylamide gel electrophoresis. The peptide map patterns of polypeptide PPA-80 in liver induced by these compounds were strikingly similar. The ultrastructural studies demonstrate that fenofibrate, ciprofibrate, LS 2265, DG 5685 and DH 6463 can induce proliferation of peroxisomes in liver cells of rats, and further confirm the previous reports of hepatic peroxisome proliferative activity of methyl clofenapate, tiadenol, bezafibrate, gemfibrozil and RMI-14514, as shown morphologically. Whether these structurally unrelated chemicals or their metabolite(s) directly activate the peroxisome specific genes to induce this multi-enzyme system or they exert their action on peroxisomes indirectly by causing fatty acid overload in hepatocytes remains to be elucidated. These chemicals offer a simple and reproducible means of stimulating peroxisomal enzymes in liver and should serve as useful tools, for evaluating the implications of hepatic peroxisome proliferation and in elucidating the mechanism of peroxisome proliferator-induced carcinogenesis.
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PMID:Evaluation of selected hypolipidemic agents for the induction of peroxisomal enzymes and peroxisome proliferation in the rat liver. 684 Jul 92

Dehydroepiandrosterone (DHEA) is a newly identified peroxisome proliferator that causes hepatomegaly, peroxisome proliferation, and induction of peroxisome-associated enzymes in rats and mice, and hepatocellular carcinomas in rats. In the present study, we have systematically analyzed sex differences and the effect of castration on DHEA-induced peroxisome proliferation in male and female rats, since no information is available on this subject. DHEA was fed in diet at a concentration of 0.45% for 2 weeks and livers were analyzed for hepatomegaly, peroxisome volume density, peroxisome proliferator associated Mr 80,000 polypeptide (PPA-80), and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) mRNA. Both intact and castrated rats showed similar response to DHEA characterized by increased peroxisome volume density, PBE mRNA, and PPA-80. Significant difference was observed in the liver weights between castrated and intact animals in both the sexes. Castrated rats that received DHEA had 20%-30% more liver weight than DHEA-administered intact rats. These results clearly indicate that peroxisome proliferative effect of DHEA is not influenced by sex hormones and it is equally potent in both males and females.
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PMID:Dehydroepiandrosterone-induced peroxisome proliferation in the rat: evaluation of sex differences. 793 49