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

The question as to whether CCl4 decreases the activities of glucose-6-phosphatase and cytochrome P-450 in liver endoplasmic reticulum mainly through its action in stimulating lipid peroxidation has been investigated using Promethazine to block lipid peroxidation. The investigation, moreover, has compared the effects of CCl4, with and without Promethazine, on isolated rat hepatocytes with corresponding effects on rat liver microsomal suspensions. Our data give no support for the view that products of lipid peroxidation are the main cause of the decrease in cytochrome P-450 observed in CCl4-intoxication. However, our present results are consistent with lipid peroxidation being a major contributory factor to the decrease in glucose-6-phosphatase activity observed in CCl4-induced liver injury.
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PMID:The role of lipid peroxidation in CCl4-induced damage to liver microsomal enzymes: comparative studies in vitro using microsomes and isolated liver cells. 626 65

Male Sprague-Dawley rats were fed a thiamine deficient diet for three weeks, then treated with a range of CCl4 doses (0.01-1-ml/kg). Rats fed the deficient diet grew more slowly (body weight 65 percent of control) and had elevated liver glutathione (GSH) (220 percent of control). CCl4 hepatotoxicity, assessed by serum glutamicpyruvic transaminase (SGPT) activity and histological examination 24 hours after the hepatotoxin, was augmented in the group fed the thiamine deficient diet. Likewise, CCl4 inhibition of liver endoplasmic reticulum (ER) function (glucose-6-phosphatase (G6Pase) and calcium pump activities one hour after CCl4) was enhanced in rats fed the deficient diet. These results suggest that thiamine deficiency enhances CCl4 damage to membranes of the ER and enhances CCl4 hepatotoxicity.
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PMID:Enhanced hepatotoxicity and inhibition of liver endoplasmic reticulum calcium pump by CCl4 in rats fed a thiamine deficient diet. 629 46

Protective effects of KB-53 on acute liver injury induced by carbon tetrachloride (CCl4) and 1-naphtylisothiocyanate (ANIT) in mice was investigated by means of histopathological, histochemical and enzymehistochemical examinations. Diffuse centrilobular necrosis, ballooning degeneration of hepatocytes and hemorrhage were markedly observed in the livers of the mice one to three days after a subcutaneous injection of CCl4. On the other hand, in the livers of KB-53 pretreated mice, forcal necrosis was observed and inflammatory cells had already infiltrated one day after CCl4-intoxication. Three days later, remarkable development of absorbent granulation tissues with syncytium and hepatocytic mitosis was observed. Furthermore, a number of PAS positive materials such as mucopolysaccharides and mucoproteins were detected in the livers of KB-53 pretreated mice. KB-53 inhibited the disappearance of glucose-6-phosphatase (G-6-Pase) in the liver after CCl4-intoxication and the rise of alkaline phosphatase (Al-Pase) in the liver after ANIT-intoxication. In addition, KB-53 inhibited the rise of Al-Pase and total bilirubin in the serum of mice after CCl4 and ANIT-intoxication. All these findings suggest that KB-53 protects liver against the morphological and functional changes, and it potentiates the proliferative and regenerative activity of the liver impaired with CCl4 and ANIT.
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PMID:[Effects of cianidanol (KB-53) on experimental liver injury in mice--histopathological, histochemical and enzyme-histochemical studies]. 631 98

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.
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PMID:Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. 750 Jun 38

Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger.
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PMID:Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase. 759 31

The chemoprotection extended by eugenol against carbon tetrachloride (CCl4) intoxication was established by studies on drug-metabolizing phase I and phase II enzymes. An overall decrease in drug-metabolizing enzymes, namely NADPH-cytochrome c reductase, NADH-cytochrome reductase, coumarin hydroxylase, 7-ethoxy coumarin-O-deethylase, UDP-glucuronyltransferase and glutathione-S-transferase, was observed with CCl4 intoxication, with a subsequent decrease in cytochrome P450 and cytochrome b5 content. CCl4 caused a significant decrease in microsomal phospholipids and the marker enzymes glucose-6-phosphatase and 5'-nucleotidase, and an increase in thiobarbituric acid reactive substances (TBARS). Simultaneous administration of eugenol with CCl4 inhibited the accumulation of TBARS and the decrease in the microsomal phospholipids and marker enzymes. Further, the chemical onslaught imposed by CCl4 on the drug-metabolizing system was removed successfully by eugenol. Eugenol appears to act as an in vivo antioxidant and as a better inducer of phase II enzymes than phase I enzymes. It is therefore suggested that eugenol could be an interesting basic structure for drug design.
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PMID:Effect of eugenol on drug-metabolizing enzymes of carbon tetrachloride-intoxicated rat liver. 778 11

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered to rats (100 mg/kg b.wt) by a single intraperitoneal injection, increases to twice its normal level in the liver microsomes. Microsomes so enriched become resistant to lipid peroxidation induced by incubation with carbon tetrachloride in the presence of a NADPH-regenerating system: also the lipid peroxidation-dependent inactivation of glucose-6-phosphatase and gamma-glutamyl transpetidase due to the haloalkane are prevented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P450IIE1, responsible for the CCl4-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the protein covalent binding of the trichloromethyl radical (CCl3 degrees), is similar to that of not supplemented microsomes treated with CCl4. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant properties rather than inhibiting the metabolism of the toxin.
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PMID:Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosterone-pretreated rats. 783 57

Low zinc (Zn) intake could be expected to compromise resistance to oxidative stress, even when accompanied by a normally protective acute phase response pretreatment. Mildly Zn deficient rats showed very high degrees of CCl4-induced hepatic cell membrane injury as assessed by serum sorbitol dehydrogenase activities. Rats pair-fed adequate Zn also showed above normal degrees of injury, but much less than rats fed low Zn. An acute phase response, elicited by leg inflammation, strongly protected rats consuming adequate Zn, either ad libitum or pair-fed, against the CCl4-induced rise in sorbitol dehydrogenase. However, the effect was partially absent in rats fed low Zn. Zinc intake had no effect on CCl4-produced microsomal injury, assessed by glucose-6-phosphatase activities. Rats fed low Zn showed normal hepatic levels of metallothionein, a Zn protein with proposed antioxidant functions, but did not show the rise in metallothionein levels normally associated with acute phase response. In summary, mild Zn deficiency caused poor resistance to CCl4-induced plasma membrane injury and partially negated acute phase response protective effects. Metallothionein was not involved in the former effect, but may have contributed to the latter.
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PMID:Effects of mild zinc deficiency, plus or minus acute phase response, on CCl4 hepatotoxicity. 829 97

Our earlier studies in vitro have shown that eugenol inhibits liver microsomal monooxygenase activities and carbon tetrachloride (CCl4)-induced lipid peroxidation (Free Rad. Res. 20, 253-266, 1994). The objective of the present investigation was to study the in vivo protective effect of eugenol against CCl4 toxicity. Eugenol (5 or 25 mg/kg body wt) given orally for 3 consecutive days did not alter the levels of serum glutamic oxalacetic transaminase (SGOT), microsomal enzymes such as cytochrome P450 reductase, glucose-6-phosphatase (G-6-Pase) xenobiotic-metabolizing enzymes (aminopyrine-N-demethylase, N-nitrosodimethylamine-demethylase and ethoxyresorufin-O-deethylase) and liver histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to each rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGOT level without appreciable improvement in morphological changes in liver. Eugenol pretreatment also did not influence the decrease in microsomal cytochrome P450 content, G-6-Pase and xenobiotic-metabolizing enzymes brought about by CCl4. Since eugenol is metabolized and cleared rapidly from the body, the dose schedule was modified in another experiment. Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally i.e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. administration of CCl4 (0.4 ml/kg) prevented significantly the rise in SGOT activity as well as liver necrosis. The protective effect was more evident at 1 mg and 5 mg eugenol doses. However, the decrease in microsomal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected. The protective effect of eugenol against CCl4 induced hepatotoxicity is more evident when it is given concurrently or soon after rather than much before CCl4 treatment.
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PMID:The protective effects of eugenol on carbon tetrachloride induced hepatotoxicity in rats. 857 54

This investigation was undertaken to determine if an interaction of toxicologic importance might occur during a prolonged exposure of rats to carbon tetrachloride (CCl4) and Dimethyl Sulphoxide (DMSO). CCl4 administration produced a significant decrease in hepatic microsomal glucose-6-phosphatase activity accompanied by a small increase in alkaline phosphatase activity, Glutathione depletion was highest when CCl4 was administered alone. DMSO, did not increase hepatic uptake of glucose. These findings suggest that DMSO given at low dose can prevent the decrease of hepatic glucose-6-phosphatase but may indirectly affect the level of tissue glucose.
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PMID:The effect of dimethyl sulphoxide on CCl4-induced damage to the liver and its effects on hepatic glutathione and glucose. 871 61


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