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)

Experimental infection of golden hamsters with Leishmania donovani caused significant alterations in the hepatic microsomal mixed function oxidase system. Gross examination of liver indicated hepatomegaly. Microsomal protein contents were only marginally elevated. Cytochrome P-450 as well as haem contents were significantly decreased and it directly correlated with the degree of infection. Cytochrome b5 exhibited elevation at lower degrees of infection which came down to control levels at the peak infection. Concomitant suppression was also noticed in cytochrome P-450 dependent monooxygenase activities, viz. aniline hydroxylase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase. No significant change was observed in NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase. The results indicate suppression of hepatic microsomal MFO activities during visceral leishmaniasis.
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PMID:Suppression of the hepatic microsomal cytochrome P-450 dependent mixed function oxidase activities in golden hamster during Leishmania donovani infection. 259 7

The influence of 1-benzylimidazole on the activities of hepatic monooxygenases cytochromes P-450 dependent, epoxide hydrolases and UDP-glucuronosyltransferases was investigated in male Wistar rats. Several doses (25, 75 and 100 mg/kg/day) were administered gastrically during 5 days in order to evaluate the dose-related induction. The treatment caused a dose-dependent hepatomegaly. 1-Benzylimidazole decreased the plasma level in triglycerides by 60-70%; by contrast the cholesterol content was not changed during the time course of the experiment. Lauric acid hydroxylase, benzphentamine N-demethylase, 7-ethoxyresorufin O-deethylase, 7-ethoxycoumarin O-deethylase activities were increased 3.5-, 4-, 13- and 46-fold, respectively with the highest dose. By immunoblotting, an enhancement in the protein bands corresponding to cytochromes P-450c and P-450b could be simultaneously observed, whatever the dose administered, thus suggesting an induction process. However, 1-benzylimidazole failed to bind with high affinity to the cytosolic Ah receptor. On the other hand, measurement of the activity of the microsomal epoxide hydrolase with benzo(a)pyrene-4,5-oxide as substrate and quantitation of the enzyme protein by immunoassay revealed that the increase in the activity after treatment with the compound was the result of enzyme activation only. By contrast, cytosolic epoxide hydrolase was not affected by 1-benzylimidazole. This compound also stimulated three distinct forms of UDP-glucuronosyltransferase. The activities towards 4-methylumbelliferone, 1-naphthol, morphine or a monoterpenoid alcohol, nopol, supported by two different isozymes were significantly increased only with the highest dose; meanwhile bilirubin glucuronidation was 2-fold enhanced, whatever the dose used. These observations emphasize the variety of the effects of 1-benzylimidazole on drug-metabolizing enzymes.
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PMID:Effect of 1-benzylimidazole on cytochromes P-450 induction and on the activities of epoxide hydrolases and UDP-glucuronosyltransferases in rat liver. 284 Sep 13

The effect of peroxidized soybean oil in the diet of male Wistar rats was studied on hepatic drug metabolizing enzymes and their phenobarbital induction and compared to that of natural soybean diet in the same conditions. No hepatomegaly or increase in serum transaminases occurred, however growth was inhibited after ingestion of peroxidized soybean oil. In addition, the protein biosynthesis of epoxide hydrase determined by immunochemistry was largely stimulated by this treatment; but the corresponding activity measured with benzo(a)pyrene 4-5 oxide as a substrate was increased in weaker proportions. This induction was limited to epoxide hydrolase only, since the enzymes of phase one were not affected and UDP glucuronosyltransferase activities toward group I substrates were randomly activated. The induction of epoxide hydrolase may affect only one or several isoforms of the membrane enzyme which are not necessarily specific to benzo(a)pyrene 4-5 oxide activity determination of the enzyme.
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PMID:[Ingestion of soybean epoxide oil. Effects on monooxygenases, epoxide hydrolase and activities of UDP glucuronosyltransferases in hepatic microsomes of the rat]. 297 40

Liver regeneration was stimulated in male rats with two-thirds of the liver removed by feeding a basal diet supplemented with acetaminophen (0.35-1.5%; weight basis), 2-acetamidophenol (1.0%) and acetophenetidin (1.0%) over a period of 10 days po, but was in the control range with the m-isomer, 3-acetamidophenol (1.0%), N-butyryl-p-aminophenol (1.0%), o-, m- and p-aminophenols (0.50%) and 4-acetamidothiophenol. In fact, the latter inhibited at a level of 0.60%. The operated young or mature female underwent no significant increase in control response with acetaminophen (1-1.5%). However, as with the male, the wet and dry liver weight percentages were markedly increased in the intact female fed acetaminophen (1.0-1.5%) as also with 2-acetamidophenol (1.0%). Liver enlargement occurred in the intact male with acetophenetidin (1.0%) but not with the N-butyryl- and thiophenol derivatives fed at 1.0 and 0.50%, respectively. Hepatic microsomal preparations from the intact and operated series showed no remarkable changes in cytochrome P-450 nor in the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase, with the more polar acetaminophen and the N-butyryl compound but the enzymes were elevated in the group fed acetophenetidin. Inductive effects on microsomal enzymes were further amplified by injection of several animals per group with phenobarbital ip daily at 80 mg/kg for the last 3 days prior to sacrifice. Increases in increments or liver weight percentages ensued over the basal values and as investigated in an intact male series, the enzymes ranged higher than the uninjected controls and with the thiophenol-fed group, exceeded those of the phenobarbital-injected controls.
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PMID:Liver regeneration and hepatic microsomal enzyme induction by acetaminophen and derivatives. 402 13

In order to understand the secondary effects of hypolipidaemic agents in human therapy, the authors have studied the inductive properties of four of these drugs, clofibrate, F1379, fenofibrate and probucol, on hepatic drug metabolizing enzymes in the rat. Each hypolipidaemic molecule was administered once a day for five days at doses ranging from 100 to 450 mg/kg/day. All the drugs tested caused hepatomegaly, the effect being particularly marked in the case of F1379 and fenofibrate; on the other hand they decreased the microsomal protein content, especially after F1379 or probucol treatment. Cytochrome P-450 concentration was not greatly affected, with only a 40% increase by clofibrate (dose 200 mg/kg/day) and by F1379 at the lower dose. It is of interest that all the hypolipidaemic agents tested enhanced the activity of epoxide hydrolase with 4, 5 benzo(a)pyrene oxide as the substrate. Except for fenofibrate and probucol at the lower dose, they all strongly increased the activity. The greatest change was effected by F1379 which led to a three to eight-fold increase over the control values. We also measured UDP-glucuronosyltransferase activities using two substrates belonging to group I (4-nitrophenol) and group II (4-hydroxybiphenyl). It appears that the changes in enzyme activity found depended both on the type and the dose of the drug administered and on the chemical structure of the substrate. This study showed that hypolipidaemic drugs which are chemically related to clofibrate could greatly modify the activity of drug metabolizing enzymes and therefore alter the transformation of drugs administered concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative study of four hypolipidaemic agents on the activity of drug-metabolizing enzymes in rat liver microsomes. 643 12

We describe four infants with a novel subtype of an isolated deficiency of one of the peroxisomal beta-oxidation enzymes with detectable enzyme protein. The patients showed characteristic clinical and biochemical abnormalities, including hypotonia, psychomotor retardation, hepatomegaly, typical facial appearance, accumulation of very-long-chain fatty acids, and decreased lignoceric acid oxidation. However, beta-oxidation enzyme proteins were detected by immunoblot analyses, and large peroxisomes were identified by immunofluorescence staining. In order to identify the underlying defect in these patients, complementation analysis was introduced using fibroblasts from these patients and patients with an established deficiency of either acyl-CoA oxidase or bifunctional enzyme, as identified by immunoblotting. In the complementing combinations, fused cells showed increased lignoceric acid oxidation, resistance against 1-pyrene dodecanoic acid/UV selection, and normalization of the size and the distribution of peroxisomes. The results indicate that two patients with a more severe clinical course were suffering from bifunctional enzyme deficiency and that the other two infants, who were siblings and had a less severe clinical presentation, were the first patients with acyl-CoA oxidase deficiency with detectable enzyme protein.
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PMID:Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. 827 68