Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mercuric chloride was administered once i.p. to female Fischer-344 rats at doses of 0, 0.2, 0.6 and 1.8 mg/kg. Although there were no alterations in the urinary excretion of lactate dehydrogenase, significant elevations in the activities of urinary (U) alkaline phosphatase, glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) indicated that mercuric chloride was nephrotoxic. There was no evidence of hepatotoxicity as hepatic glucose-6-phosphatase and serum sorbitol dehydrogenase were essentially unaffected by mercuric chloride administration. The activities of ethylmorphine demethylase, hexobarbital oxidase and aldrin epoxidase determined in vitro were not inhibited by mercuric chloride although aniline hydroxylase activity was decreased. Of the four phase-II reactions measured, only the glucuronidation of chloramphenicol was diminished by treatment with mercuric chloride. Results from the in vivo studies on the metabolism of lindane, which indicated no change in the excretion of free or conjugated metabolites, were in close agreement with the in vitro data suggesting that the nephrotoxic effects of mercuric chloride do not alter the urinary excretion of the model substrate lindane.
 ...
PMID:A comparison of in vitro and in vivo methods for evaluating alterations in hepatic drug metabolism following mercuric chloride administration. 242 44

Oral administration of pulegone (400 mg/kg) to rats once daily for five days caused significant decreases in the levels of liver microsomal cytochrome P-450 and heme. Cytochrome b5 and NAD(P)H-cytochrome c-reductase activities were not affected. Massive hepatotoxicity accompanied by an increase in serum glutamate pyruvate transaminase (SGPT) and a decrease in glucose-6-phosphatase were observed upon treatment with pulegone. A significant decrease in aminopyrine N-demethylase was also noticed after pulegone administration. Menthone or carvone (600 mg/kg), compounds related to pulegone, when administered orally did not cause any decrease in cytochrome P-450 levels. The hepatotoxic effects of pulegone were both dose and time dependent. Pretreatment of rats with phenobarbital (PB) or diethylmaleate (DEM) potentiated the hepatotoxicity caused by pulegone, whereas, pretreatment with 3-methylcholanthrene (3-MC) or piperonyl butoxide protected from it. It appears that a PB induced cytochrome P-450 catalysed reactive metabolite(s) may be responsible for the hepatotoxicity caused by pulegone.
 ...
PMID:Hepatotoxicity of pulegone in rats: its effects on microsomal enzymes, in vivo. 254 21

Oxidation of diethyldithiocarbamate (DTC) to disulfiram (DS) by liver microsomes was tested in vitro by using a copper-DTC chelate formation reaction after the conversion of DS to DTC by glutathione (GSH). In the presence of NADPH, microsomes produced DS from DTC in both the free and microsome-bound forms, the former being greater than the latter. DS production was dependent on NADPH and DTC concentrations, and incubation time. Increases in microsomal concentrations, up to a certain level, also increased the free and total DS production. NADH was only somewhat effective, both the exposure to a nitrogen atmosphere and heat-denaturation of the microsomes suppressed the reaction. Preincubation of microsomes with both DTC and NADPH markedly decreased aniline hydroxylase, p-nitroanisole O-demethylase and glucose-6-phosphatase activities, and moderately decreased NADH-ferricyanide and NADH-cytochrome c reductase, but NADPH-cytochrome c reductase was minimally affected. DTC alone had only slight effects on the activities. DS also decreased these enzyme activities, particularly glucose-6-phosphatase; the loss of NADPH-cytochrome c reductase activity being protected in the presence of NADPH. GSH almost completely prevented the loss of microsomal enzyme activities induced by DTC and NADPH except for the drug metabolizing activities, in which protection was incomplete. The microsomal oxidation of DTC to DS could play a role in the action of DS in the liver, since DS is rapidly degradated to DTC in vivo.
 ...
PMID:Oxidation of diethyldithiocarbamate to disulfiram by liver microsomes in the presence of NADPH and subsequent loss of microsomal enzyme activity in vitro. 285 81

Propylene is hepatotoxic to male Charles River COBS Sprague-Dawley rats pretreated with polychlorinated biphenyls (PCB: Aroclor 1254). Four-hour inhalation exposure to 50,000 ppm propylene increased liver weight/body weight ratios and elevated serum enzyme activities in PCB-pretreated animals. Hepatic microsomal cytochrome P-450 content of PCB-pretreated rats dropped profoundly during propylene exposure and remained depressed for at least 24 h. In addition, PCB-pretreated, propylene-exposed rats exhibited a decrease in the specific activity of hepatic microsomal aniline hydroxylase. However, there was no change in activities of either hepatic microsomal aminopyrine demethylase or glucose-6-phosphatase. Propylene exposure of rats pretreated with beta-naphthoflavone (BNF), phenobarbital (PB), or a mixture of BNF and PB was not hepatotoxic. However, there was, in these animals, a substantial decline in hepatic microsomal cytochrome P-450 levels 24 h after the start of propylene exposure. Hence, the propylene-dependent process resulting in hepatic cytochrome P-450 destruction is qualitatively or quantitatively different from the process that causes acute hepatotoxicity. Preexposure fasting had no effect on the hepatotoxicity resulting from a 4-h exposure of PCB-pretreated rats to 50,000 ppm propylene. Administration of SKF-525A to PCB-pretreated rats immediately prior to propylene exposure completely prevented elevations in serum enzyme activities and liver weight/body weight ratios. In vitro incubation of hepatic microsomes prepared from either BNF-, PB-, or PCB-pretreated rats with an atmosphere of 20% propylene/80% air produced in NADPH-dependent decrease in cytochrome P-450 content. These results suggest that PCB pretreatment is a prerequisite for propylene hepatotoxicity in the rat. Cytochrome P-450-dependent bioactivation of propylene is associated with this hepatotoxicity, but further studies are needed to characterize the mechanism of the PCB-propylene interaction.
 ...
PMID:Mixed-function oxidase system induction and propylene hepatotoxicity. 298 38

We determined whether alterations in hepatic microsomal function occur in association with iron-induced lipid peroxidation in vivo in rats with chronic dietary iron overload. In rats fed a 2.0% carbonyl iron diet for a period of 20 wk, there was no significant microsomal conjugated diene formation (evidence of microsomal lipid peroxidation) or difference in cytochrome P450 concentration found at mean (+/- SEM) hepatic iron concentrations of 1210 +/- 92 micrograms/g liver (wet wt) or 2730 +/- 100 micrograms/g. At a hepatic iron concentration of 4090 +/- 245 micrograms/g, however, there was significant conjugated diene formation (p less than 0.001) and a 56% decrease in the cytochrome P450 concentration (p less than 0.001). In rats fed a 2.5% carbonyl iron diet for 10 wk, achieving a liver iron concentration of 4820 +/- 420 micrograms/g, there was significant microsomal conjugated diene formation (p less than 0.001), a 35% reduction in cytochrome P450 (p less than 0.005), and a 16% reduction in aminopyrine demethylase activity (p less than 0.025), but only an 8% reduction in glucose-6-phosphatase activity (p = not significant). Finally, in rats fed a 3.0% iron-supplemented diet for 7 wk, achieving a liver iron concentration of 2730 +/- 205 micrograms/g, there was a 23% reduction in cytochrome P450 (p less than 0.025), a 28% reduction in cytochrome b5 (p less than 0.001), and a 47% increase in heme oxygenase activity (p less than 0.025) (heme oxygenase activity measured in this group only). We conclude that oral iron loading can produce microsomal lipid peroxidation in vivo that is associated with selective decreases in microsomal hemoprotein concentrations and cytochrome P450-dependent enzymes.
 ...
PMID:Hepatic microsomal function in rats with chronic dietary iron overload. 300 59

Plasmodium yoelii nigeriensis infection in albino mice significantly altered the hepatic microsomal mixed function oxidase system. Cytochrome P-450 (the terminal monooxygenase) and other monooxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase were significantly lowered while microsomal heme showed 4-fold increase at 80% parasitaemia. Noticeable impairment in the other components like NADH:cytochrome b5 reductase, NADPH:cytochrome c reductase, cytochrome b5 and glucose-6-phosphatase was also observed. Oral treatment of normal and P. y. nigeriensis infected mice with chloroquine (64 mg per kg body weight for 4 days) caused lowering of mixed function oxidase activities which however showed a recovering trend, a week after cessation of treatment.
 ...
PMID:Effect of Plasmodium yoelii nigeriensis infection and chloroquine on the hepatic mixed function oxidase system of mice. 362 73

The effects of high-dose indomethacin (three daily dose, 8.5 mg/kg ip) on pathology and histology, on serum and urine biochemistry, and on various hepatic enzyme activities were studied in rats. Hepatic cytochrome P-450 and aminopyrine N-demethylase were decreased by 52-62%, but glucuronyl transferase fell by only 22%. Hepatic glucose-6-phosphatase, aryl esterase, 6-phosphogluconate dehydrogenase and sulphotransferase remained unchanged, while glucose-6-phosphate dehydrogenase increased by 29%. There were no widespread changes in hepatic and renal pathology or histology, but noteworthy was a mild, focal, centrilobular hepatic response. By contrast, there were severe intestinal lesions: the effects on hepatic enzymes might have been partly a consequence of the intestinal damage. There was a reversible uraemia and significant decreases (20-40% below normal) in both serum albumin and protein, while serum levels of creatinine and aspartate-amino-transferase activity remained constant. A reversible N-acetyl-beta-D-glucoseaminidase (NAG) enzymuria occurred (300% above normal), but no significant proteinuria (less than 300 mg/l). Administration of 16, 16-dimethylprostaglandin F2 alpha(0.5 mg/kg iv) concomitantly with the indomethacin greatly ameliorated the intestinal lesions and prevented the decreases in hepatic drug-metabolizing enzymes. Concomitant 16,16-dimethylprostaglandin F2 alpha did not, however, influence the indomethacin-induced decreases in serum protein, albumin or NAG-enzymuria. It was concluded that indomethacin had a highly selective effect causing a decrease in hepatic cytochrome P-450, which was not accompanied by severe damage to hepatocyte structure.
 ...
PMID:Comparative effects of indomethacin on hepatic enzymes and histology and on serum indices of liver and kidney function in the rat. 393 37

Fischer 344 male rats were treated with N-nitrosodiethylamine, and two weeks later promotion was effected by treatment with N-2-acetylaminofluorene for 14 days. At midpoint of the promotion protocol, one group of rats was subjected to partial hepatectomy (model A); others were treated with either carbon tetrachloride (model B) or thioacetamide (model C). Alterations in the activities of marker enzymes (glucose-6-phosphatase, gamma-glutamyl transpeptidase, cytochrome P-450, N-demethylase) during hepatocarcinogenesis were followed biochemically. The highest incidences of liver foci and of hepatocellular carcinomas were observed in model A, and these showed a good correlation with long-lasting elevated gamma-glutamyl transpeptidase activity. Analysis of the marker alterations suggests that there are three stages in hepatocarcinogenesis: (1) depression resulting from the toxic action of the initiator; (2) recovery and adaptation to cellular injury; and (3) long-lasting adverse alterations in the activities of the marker enzymes after promotion. The loss of certain non-histone proteins soon after promotion was also observed. Comparative studies of the individual actions of initiators and promoters on marker enzymes indicated that both contribute to the marker changes during hepatocarcinogenesis.
 ...
PMID:Alterations of markers during hepatocarcinogenesis in rats. 615 22

Previous work has established the marked potentiation of CCl4 hepatoxicity by prior exposure to chlordecone (CD). This study was conducted to determine if prior exposure to CD results in enhancement of CCl4-induced destruction of the hepatic microsomal mixed-function oxygenase (MFO) system. Male Sprague-Dawley rats received a single oral dose of CD (10 mg/kg) or corn oil vehicle alone (1 ml/kg) 24 hr prior to a single ip injection of CCl4 (0-100 microliter/kg). Mirex (M; 10 mg/kg) and phenobarbital (PB; 80 mg/kg/day for two days) were used as negative and positive controls respectively for the potentiation of CCl4 hepatotoxicity. Hepatotoxicity was evaluated 24 hrs after CCl4 administration by elevations of three serum enzymes (GPT, GOT, and ICD). The key hepatic microsomal MFO parameters measured were microsomal protein, cytochrome P-450 content, glucose-6-phosphatase (G-6-Pase), and aminopyrine demethylase (APD). As previously demonstrated using a subchronic dietary pretreatment protocol, CD potentiated CCl4 hepatotoxicity over a range of CCl4 doses to a greater extent than PB or M, as judged by elevations in serum enzymes. PB caused the greatest increase in total P-450 content and the greatest increase in CCl4-mediated destruction of microsomal protein and APD activity. M caused the least destruction of total hepatic cytochrome P-450, despite the same level of cytochrome P-450 as in the PB group. CD treatment caused the greatest decrease in G-6-Pase activity in comparison to PB or M pretreatments and a similar degree of P-450 destruction as observed with the PB group. These findings suggest that in general, CCl4-induced destruction of hepatic MFO parameters measured in this study is disproportional to the known degree of potentiated hepatotoxicity by the pretreatments and does not accurately reflect the potentiation of CCl4 hepatotoxicity by CD.
 ...
PMID:Destruction of hepatic mixed-function oxygenase parameters by CCl4 in rats following acute treatment with chlordecone, Mirex, and phenobarbital. 619 92

Five min after administration of a single, i.p. dose of ammonium metavanadate (5 mg/kg), in rats, liver enzyme activities were measured. Microsomal mixed-function oxidases (except for aminopyrine N-demethylase), glucose-6-phosphatase and alkaline phosphatase were inhibited but lactate, malate, and glycerophosphate dehydrogenases as well as microsomal NADPH2-dependent cytochrome c reductase were unchanged.
 ...
PMID:Effects of ammonium metavanadate on rat liver enzymes. 660 66


<< Previous 1 2 3 4 Next >>