Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Swiss-Webster mice were fed diets containing four hypolipidemic agents which are known to induce proliferation of hepatic peroxisomes. Treatment with all four drugs (clofibrate; its structural analogue, nafenopin; and two drugs structurally unrelated to clofibrate, tibric acid and Wy-14,643) produced a marked hepatomegaly in the mice. The extent of the increase in liver weight correlated well with the increases in total hepatic DNA and in the collective volume of hepatocyte peroxisomes. Treatment with these drugs also produced similar increases in the activities of peroxisome-associated enzymes. The most dramatic increases were noted in the activities of the short-chain (8- to 26-fold) and medium-chain (4- to 11-fold) carnitine acyltransferase. Significant increases were also noted in the activities of catalase (twofold to threefold), alpha-glycerophosphate dehydrogenase (twofold to threefold) and the long-chain carnitine acyltransferase (twofold to fourfold). Activity of the latter enzyme, however, is not known to be associated with peroxisome fractions. Concomitant administration of actinomycin D or cycloheximide with a single oral dose of clofibrate diminished the increases in liver weight and carnitine acyltransferase which occurred with clofibrate treatment alone. The finding that the major increase in activity of peroxisome enzymes occurred in those associated with metabolism of acyl CoA groups supports the hypothesis that the hypolipidemic action of the drugs and the proliferation of hepatic peroxisomes are related functions.
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PMID:The hepatic effects of hypolipidemic drugs (clofibrate, nafenopin, tibric acid, and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. 62 9

Administration of BR-931, an ethanolamine derivative of Wy-14,643 [4-chloro-6-(2,3-xylidino)-2-pyrimidinythio]acetic acid, at a dietary concentration of 0.125% for 3 weeks to male F-344 rats, resulted in a significant enlargement of the liver. The hepatomegaly appeared to be due to liver cell hyperplasia and hypertrophy resulting, in part, from peroxisome and smooth endoplasmic reticulum proliferation. The hepatic catalase and carnitine acetyltransferase activities increased significantly in association with peroxisome proliferation. The hepatomegaly and peroxisome proliferation induced by BR-931 were comparable in degree to those resulting from feeding of an equivalent dose of Wy-14,643. All these hepatic effects were reversible when the drugs were withdrawn from the diet. Screening of new compounds for hepatic peroxisome proliferation and for increases in peroxisome-associated enzymes may prove to be an adjunct to evaluating their potency as hypolipidemic agents, in view of frequent association between hepatic peroxisome proliferation and hypolipidemia.
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PMID:Hepatic peroxisome proliferation: induction by BR-931, a hypolipidemic analog of WY-14,643. 70 42

6-Chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid hydrochloride lowered serum cholesterol, triglyceride, phospholipid, and free fatty acid levels in normal rats. The compound appeared to have a low toxicity and to be well tolerated in mice, adult and neonatal rats, and rabbits. At hypolipidemic doses, it caused a slight hepatomegaly associated with an increase in liver phospholipid and protein content. Liver N-demethylase and catalase activities were increased by the drug treatment. This acid had no in vitro antilipolytic activity and did not affect serum desmosterol-cholesterol ratios. The results indicate that it has a mechanism of action similar to clofibrate.
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PMID:Serum lipid-lowering properties of 6-chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid. 84

The comparative hypolipidemic and hepatic peroxisome proliferative activities of a series of thioacetic acid pyrimidines were evaluated in male mice. [4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643) produced significant hepatomegaly and peroxisome proliferation in liver cells. This compound also increased the hepatic catalase and carnitine acetyltransferase activities and lowered serum cholesterol and triglyceride levels. The structurally related analogs, Wy-15,690, Wy-15,672, Wy-15,746 and Wy-15,496, which lacked hypolipidemic effect failed to induce hepatomegaly and peroxisome proliferation. No substantial increase in catalase and carnitine acetyltransferase activities was noted. It is concluded that the hepatic peroxisome proliferative effect is closely related to the hypolipidemic activity, rather than to any specific chemical structure.
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PMID:Hepatic effects of some [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (WY-14,643) analogs in the mouse. 85 95

Some hepatic effects of the hypolipidemic agents 3,9-di-3-pyridyl-2,4,8,10-tetraoxaspiro-5,5-undecane (compound A) and 2-(4-dibenzofuranyloxy)-2-methylpropionic acid (compound B) were investigated in male rats. The animals were treated orally with these drugs and a reference compound-clofibrate for 10 weeks, the daily doses being 250, 300 and 300 mg/kg body weight respectively. All three drugs caused hepatomegaly with a normal microscopic appearance in liver cells. In rats given compound A, part of some liver cells could be occupied by numerous membranes of smooth endoplasmic reticulum. The hepatocytes of the rats treated with compound B or clofibrate showed a marked increase in microbody profiles and an elevated hepatic catalase activity in comparison to the control animals. Neither the microbodies nor the catalase activity were affected by compound A. Hypolipidemic effects were demonstrated with all three compounds, the most potent activity being shown by compound B. Treatment with this agent resulted in significantly higher catalse activity than with clofibrate.
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PMID:Hepatic effect of two hypolipidemic drugs in rats. 91 35

Peroxisome-deficient disorders including Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease are characterized by hypotonia, psychomotor delay, hepatomegaly and dysmorphism. Multiple peroxisomal enzymes are deficient in these disorders probably due to the defect of transport machinery of enzymes. Defects of beta-oxidation enzymes causes an accumulation of very-long-chain fatty acids, which is closely related to the pathogenesis. Catalase, a marker enzyme of peroxisome, is distributed in the cytosol. Immunocytochemical staining of peroxisomes using anti-catalase is a useful tool for prenatal and postnatal diagnosis. Although the primary etiology of peroxisomal deficiency has not been determined, genetic heterogeneity was clarified by complementation studies. At least 8 genes are involved in the formation of functional peroxisomes.
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PMID:[Clinical biochemical and genetic aspects of peroxisome-deficient disorders]. 137 33

Previous studies suggest that thyroid hormones are involved in the mechanism of peroxisome proliferation. However, those studies utilized either surgically thyroidectomized animals, which are also parathyroidectomized, without calcium supplementation, or animals pretreated with antithyroid drugs, which are known to produce metabolic as well as morphometric changes in the liver. Therefore, these animal models confound conclusions drawn in previous studies. The purpose of the present study was to investigate the role of thyroid hormones in peroxisomal proliferation by the phthalate ester plasticizer, di-(2-ethylhexyl)phthalate (DEHP) in thyroidectomized rats with parathyroid replants. Using this model, it was found that DEHP-induced hepatomegaly was partially dependent on thyroid hormones. DEHP produced a thyromimetic effect, inducing the activity of malic enzyme and carnitine acetyltransferase in the absence of thyroid hormones. Additionally, DEHP-induced activities of catalase were shown to be dependent on thyroid hormones, whereas the thyroid status of the animal had no effect on DEHP-induced activities of the peroxisomal beta-oxidizing enzymes. These data further confirm that endocrine factors play variable roles in the process of induction of various peroxisomal enzymes caused by peroxisome proliferators.
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PMID:Induction of peroxisomal enzyme activities by di-(2-ethylhexyl) phthalate in thyroidectomized rats with parathyroid replants. 146 23

The dose-response for key hepatic effects of the peroxisome proliferator ciprofibrate, 2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2- methylpropanoic acid, was delineated in mice and strain differences in response were demonstrated. Ciprofibrate was fed at concentrations ranging from 0.1 to 250 ppm to male C57BL/6N and BALB/c mice and the induction of hepatic acyl-CoA oxidase and catalase, peroxisomal enzymes involved in the formation and degradation of hydrogen peroxide, and liver hepatomegaly and mitogenesis were measured. No effect was found for enzyme induction at 5.0 ppm or less in either strain. Likewise, hepatomegaly was not found at 5.0 ppm, but mitogenesis was observed in BALB/c mice at 1.0 ppm. C57BL/6N mice demonstrated greater basal and postexposure acyl-CoA oxidase activity than BALB/c mice, while BALB/c mice demonstrated greater catalase activity and induction of liver mitogenesis. The threshold exposure level for induction of acyl-CoA oxidase activity was approximately the same as that for induction of mitogenesis in C57BL/6N mice; in contrast, the threshold exposure level for induction of acyl-CoA oxidase activity was at least one order of magnitude greater than that required for induction of mitogenesis in BALB/c mice. Thus, the induction of the peroxisomal enzyme involved in the formation of hydrogen peroxide and increased mitogenesis are not mechanistically linked. The differential effects observed in the two mouse strains provide the basis for development of a quantitative model of peroxisome proliferator-induced carcinogenicity in which cellular effects can be related to carcinogenicity.
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PMID:Dose-response relationships of hepatic acyl-CoA oxidase and catalase activity and liver mitogenesis induced by the peroxisome proliferator ciprofibrate in C57BL/6N and BALB/c mice. 156 28

A wide variety of compounds, including hypolipidemic drugs, plasticizers and other industrial chemicals, have been found to cause liver enlargement and hepatic peroxisome proliferation by mechanisms that are unclear. Although thyroid and sex hormones have been shown to modulate the hepatic response to these chemicals, the role of adrenal hormones in these phenomena is not clear, and a few studies have produced conflicting data. Therefore this study was undertaken to investigate the role of adrenal hormones in hepatomegaly and peroxisomal enzyme induction caused by peroxisomal proliferators and to further delineate the interrelationship between these parameters. Because adrenalectomy alters hepatic drug metabolism, we have used the nonmetabolizable proliferator perfluorooctanoic acid. Our data show that hepatomegaly caused by perfluorooctanoic acid depends on corticosterone, the major glucocorticoid in rodents. Liver growth caused by perfluorooctanoic acid appears to be predominantly hypertrophic in nature, and DNA synthesis in response to perfluorooctanoic acid predominates in periportal regions of the liver lobule. Data also show that although induction of peroxisomal beta-oxidation by perfluorooctanoic acid is independent of adrenal hormones, induction of catalase is dependent on the presence of these hormones. This study supports the contention that induction of activities of various peroxisomal enzymes is controlled by different regulatory mechanisms.
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PMID:Regulation of perfluorooctanoic acid--induced peroxisomal enzyme activities and hepatocellular growth by adrenal hormones. 173 36

Dehydroepiandrosterone (DHEA) treatment is effective in the prevention of various genetic and induced disorders of mice and rats. In studies designed to define some of the basic mechanisms that underline the beneficial chemopreventive effects exerted by the action of this steroid, we found that the liver undergoes profound changes that result in: (i) hepatomegaly; (ii) color change from pink to mahogany; (iii) proliferation of peroxisomes; (iv) increased cross-sectional area and volume density of peroxisomes; (v) increased or decreased number of mitochondria per cell; (vi) decreased mitochondrial cross-sectional area; (vii) marked induction of the peroxisomal bifunctional protein enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase; (viii) increased activities of enoyl-CoA hydratase and other peroxisomal enzymes assayed in this study, viz. catalase, carnitine acetyl-CoA transferase, carnitine octanoyl-CoA transferase, and urate oxidase; and (ix) increased activity of mitochondrial carnitine palmitoyl-CoA transferase. In addition, feeding DHEA to mice resulted in increased plasma cholesterol levels in two strains of mice evaluated in this study, and either slightly decreased or markedly increased plasma triglyceride levels, depending on the strain. Whether liver peroxisome proliferation, induced by DHEA feeding to mice and rats, plays a role in the chemopreventive effects elicited by this steroid remains to be established.
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PMID:Peroxisome proliferation and induction of peroxisomal enzymes in mouse and rat liver by dehydroepiandrosterone feeding. 213 91


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