Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The saponins (ASI, SK) used in this study was extracted from the root of Astragalus membranaceous Bge and Astragalus sieversianus Pull. ASI and SK were found to protect liver from chemical injury induced by CCl4, D-galactosamine and acetaminophen in mice. The two saponins were shown to impede the elevation of SGPT level, decrease the MDA content and increase the GSH concentration in mouse liver. Obvious improvement of histological changes were also observed. The protective action of ASI and SK against the hepatotoxicity was also shown in experiments using primary cultured rat hepatocytes. The average value of GPT in the medium treated with different concentration of ASI and SK (0.00075-0.18 mmol/L) was lower than that in control. Analyzing through multiple linear correlation, we showed that the lowering of SGPT was negatively related to the increase of GSH, positively related to the decrease of MDA in mice given CCl4 or acetaminophen in combination with ASI or SK. These results indicate that the hepato-protective effects of ASI and SK may be due to their anti-oxidation activities, since the content of liver protein in mice given ASI or SK was more than that in the controls. Moreover, the level of hepatic microsomal cytochrome P-450 in all mice given the two saponins were significantly increased, the liver metabolism and immunoregulating action produced by ASI and SK may be also involved in their hepato-protective effects.
 ...
PMID:[Effects of astragalus (ASI, SK) on experimental liver injury]. 144 65

The capability of the newborn rat liver to detoxify aflatoxin B1 (AFB1), a potent hepatocarcinogen is not well understood. Our present results show that immature rats are deficient in the hepatic key factors involved in biotransformation of AFB1. The activities of cytosolic glutathione S-transferases and microsomal cytochrome P-450 along with cellular glutathione (GSH) content show postnatal developmental changes. The ability of hepatic subcellular preparation from newborn rats to convert AFB1 to its reactive epoxide form, is reported for the first time in this communication. Epoxidation of [3H]AFB1 in the presence of liver microsomes from different age-groups as measured by its adduct formation to calf thymus DNA in vitro shows that newborn rats are capable of catalyzing only minimal AFB1-DNA binding compared with that of adults. Addition of cytosolic fraction of various age groups to the system suggests that young rats are less efficient in modulating the binding as compared with adults. The amount of AFB1-GSH conjugate formed is also significantly higher when adult GSH S-transferase is involved in the system. These observations show that immature liver is less efficient than a mature organ in handling a chemical carcinogen and the metabolism of AFB1 by neonatal liver differs from that in the adult.
 ...
PMID:Comparison of aflatoxin B1-DNA binding and glutathione conjugate formation by liver preparations from rats of different ages. 145 Oct 98

The effects of nickel (Ni) on hepatic monooxygenase activities (aniline 4-hydroxylase, AH; ethylmorphine N-demethylase, EMND; aminopyrine N-demethylase, AMND), cytochrome P-450, cytochrome b5, microsomal haem and reduced glutathione (GSH) levels, and glutathione S-transferase (GST) activities toward several substrates (1, chloro-2-4-dinitrobenzene, CDNB; 1,2 dichloro-4-nitrobenzene, DCNB; ethacrynic acid, EAA) in mice, rats and guinea-pigs were studied. Ni (59.50 mg NiCl2.6H2O/kg, subcutaneously) was administered to the animals 16 hr prior to sacrifice. Ni significantly inhibited AH, EMND, AMND activities, and decreased cytochrome P-450, cytochrome b5 (except in the livers of rats), and microsomal haem levels in the livers of all the animal species examined. However, the depressions were more profound in livers of mice than in those of the other two species. The hepatic GSH level was significantly inhibited in mice whereas no alteration was observed in rats. In guinea-pigs, the hepatic GSH level was significantly increased by Ni. The hepatic GST activity toward the substrate CDNB was significantly depressed in mice, unaltered in rats and significantly increased in guinea-pigs by Ni. The hepatic GST activity toward DCNB was significantly inhibited in mice whereas no significant alteration was observed in rats. In guinea-pigs, Ni caused significant increase in hepatic GST activity for DCNB. However, hepatic GST activity toward EAA was significantly inhibited in mice whereas significantly increased in rats and guinea-pigs. These results seem to indicate that i) there exists quantitative, but not qualitative, differences among the hepatic monooxygenases of rodents in response to Ni, mice being more sensitive than rats and guinea-pigs, ii) the influence of Ni on hepatic GSH level varies depending on the animal species and iii) the hepatic GSTs of rodents are differentially regulated by Ni.
 ...
PMID:Responses of hepatic xenobiotic metabolizing enzymes of mouse, rat and guinea-pig to nickel. 148 May 52

Male Sprague-Dawley rats were exposed whole-body to the mainstream smoke produced by a commercial filter cigarette for 8 consecutive days, accounting for a cumulative exposure to the smoke of 75 cigarettes. Liver and lung S12 fractions were used in the Salmonella mutagenicity test in order to assess either the decrease of potency of a direct-acting mutagen (sodium dichromate) or the metabolic activation of promutagens, including cigarette smoke itself and its condensate, benzo[a]pyrene and its 7,8-diol, the aromatic amine 2-aminofluorene, and the heterocyclic amine 3-amino-1-methyl-5H-pyrido(4,3)indole. Moreover, individual biochemical parameters were measured in the liver and lung of the same rats and, in the case of cytochrome P-450-dependent monooxygenases, also in the heart of untreated or Aroclor-treated rats. The monitored biochemical parameters included aryl hydrocarbon (benzo[a]pyrene) hydroxylase and ethoxyresorufin deethylase in microsomal fractions, epoxide (benzo[a]pyrene-4,5-oxide) hydrolase in both microsomal and cytosolic fractions, glutathione (GSH) and GSH S-transferase in the cytosol. Exposure to cigarette smoke resulted in a number of significant metabolic changes, as compared to sham-exposed rats. The most pronounced alterations consisted in a 2.6-fold induction of aryl hydrocarbon hydroxylase in the lung and 8-fold induction of ethoxyresorufin deethylase in the liver, and in a marked stimulation of the liver metabolic activation of all promutagens. The last effect was inhibited by the oral administration of the chemopreventive agent N-acetylcysteine. On the whole, there was a poor correlation between the monitored biochemical and mutagenicity endpoints.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Metabolic alterations produced by cigarette smoke in rat lung and liver, and their modulation by oral N-acetylcysteine. 151 14

1. The hepatotoxic effects of heroin and methadone, and the effect of ethanol on opioid-induced hepatotoxicity, have been investigated in human cultured hepatocytes. Hepatocytes pretreated with 50 and 100 mM ethanol were exposed to increasing concentrations of heroin and methadone. 2. Cytotoxicity was evaluated by measuring leakage of intracellular lactate dehydrogenase, and by assessment of hepatocyte mitochondrial succinate dehydrogenase. The half-maximal cytotoxic concentration of heroin for human hepatocytes (TC50) was decreased by 70-55% by pre-exposure to 50 mM ethanol, and that for methadone was decreased by 60-40%. 3. Metabolic functions of human hepatocytes were significantly impaired at concentrations of opioids that had shown little cytotoxicity. Ethanol potentiated opioid-induced hepatotoxicity; concentrations of heroin and methadone that had little or no effect on hepatocyte metabolism in the absence of ethanol caused a significant decrease in urea synthesis rate, metabolism of glycogen and depletion of the intracellular GSH pool after ethanol pretreatment. 4. The increase in toxicity of heroin and methadone produced by ethanol is concomitant with a 40% increase in cytochrome P-450 levels of the pretreated hepatocytes.
 ...
PMID:Potentiation of heroin and methadone hepatotoxicity by ethanol: an in vitro study using cultured human hepatocytes. 152 68

The effects of repeated exposure to N,N-dimethylformamide (DMF) on hepatic microsomal monooxygenase system and glutathione metabolism were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1 week. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 1 week of exposure to DMF. Hematological changes were not detected. In exposed rats, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, cholinesterase and total cholesterol significantly increased. Hepatic microsomal cytochrome P-450 and protoheme decreased by 34% and 24%, respectively, while microsomal protein and cytochrome b5 were not affected. NADH-ferricyanide reductase activity decreased by 24% while NADPH-cytochrome c reductase activity showed no change. Glutathione reductase (GR) activity showed a significant decrease after the first injection and remained depressed throughout the study, with no change in glutathione peroxidase (GPx) activity. Glutathione S-transferase (GST) activity showed a significant increase at 3 days after DMF treatment and gradually increased by 66% at 1 week. In a subsequent experiment with a single administration of DMF (4 ml/kg), reduced glutathione (GSH) in the liver was decreased by 28% at 8 h, but recovered to control levels by 24 h. These results indicate that DMF alters the hepatic microsomal monooxygenase system and glutathione metabolism. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.
 ...
PMID:Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats. 153 72

This investigation was designed to determine whether biliary excretion of bromobenzene(BB)-glutathione(GSH) conjugate can be used as an index of in vivo activation of BB. In order to test this hypothesis, the effect of chemicals known to alter the toxicity and biotransformation of BB (i.e., cytochrome P-450 inducers and inhibitors) on the biliary excretion of BB-GSH was studied in rats. BB-GSH was the major BB metabolite in bile. A linear relationship was observed between the dosage of BB administered and BB-GSH excreted into bile, up to a dosage of 250 mumol/kg of BB. Of the inducers tested, phenobarbital, which is known to increase the toxicity of BB, dramatically increased (700%) the rate of biliary excretion of BB-GSH over that in control animals. In contrast, 3-methylcholanthrene, which is known to decrease the hepatotoxicity of BB, decreased the biliary excretion of BB-GSH (56%). Inhibitors of P-450, such as SKF 525-A and piperonyl butoxide which are known to decrease the activation and hepatotoxicity of BB, also decreased the biliary excretion of BB-GSH. These findings are in agreement with the hypothesis that the biliary excretion of BB-GSH reflects the formation of the reactive BB metabolite in liver and the rate of biliary excretion can be used to determine factors that are important in determining the toxicity of BB.
 ...
PMID:Bromobenzene-glutathione excretion into bile reflects toxic activation of bromobenzene in rats. 157 Jun 37

Xenobiotics metabolized in rat pulmonary tissue are often selectively cytotoxic to individual lung cell populations. A non-homogeneous distribution of xenobiotic biotransformation enzymes, e.g., cytochrome P-450 (P-450)- and glutathione (GSH)-associated enzymes, in rat lung tissue may underlie this observed cell-selective pneumotoxicity. To evaluate this hypothesis, the relative activities of P-450- and GSH-associated enzymes were measured in sonicated, freshly isolated preparations containing enriched complements of individual toxicant-sensitive lung cell types, including non-ciliated bronchiolar epithelial (Clara) cells (24% pure), alveolar type II cells (86% pure) and pulmonary endothelial cells (identified by membrane-associated angiotensin converting enzyme activity). Lung cell fractions were isolated by centrifugal elutriation from male F344 rats that 48 h earlier received a single i.p. injection of either P-450-inducer beta-naphthoflavone (50 mg beta-NF/kg body weight) or corn oil vehicle. The enriched Clara cell fraction possessed (per 10(6) cells) greater P-450 and reduced GSH contents and higher enzyme activities (i.e., NADPH- and NADH cytochrome c reductases, benzyloxy (BROD)-, pentoxy (PROD)- and etoxyresorufin (EROD)-O-dealkylases, GSH transferase, GSH peroxidase, GSH reductase and NADPH quinone oxidoreductase) than either the enriched type II cell or endothelial cell preparations. However, the relative biochemical activities for the enriched fractions (Clara greater than type II greater than endothelial) generally reflected respective sonicate cellular protein content. Treatment of rats with beta-NF resulted in: (a) an induction in EROD activity in the enriched preparations of type II cells, Clara cells and endothelial cells (125-, 89- and 35-fold, respectively); (b) higher NADPH quinone oxidoreductase activities, which were increased to the greatest degree (3-fold) in the enriched type II cell fraction and (c) a small elevation in GSH transferase activity measured in the enriched Clara cell fraction. Although the enriched rat lung cell preparations possessed unique biochemical profiles for constitutive and beta-NF-inducible P-450- and GSH-associated enzymes, additional studies with higher purity preparations (e.g., Clara cells) will be required to more fully evaluate the relationship between relative cellular complements of xenobiotic biotransformation enzymes and pneumotoxicant susceptibility.
 ...
PMID:Cytochrome P-450- and glutathione-associated enzyme activities in freshly isolated enriched lung cell fractions from beta-naphthoflavone-treated male F344 rats. 160 25

In mice depleted of glutathione (GSH) by treatment with DL-buthionine sulfoximine (BSO), thiabendazole [2-(4'-thiazolyl)benzimidazole, TBZ] produces renal damage characterized by increases in relative kidney weight and serum urea nitrogen (SUN) concentration. Several thiazole and benzimidazole compounds related to TBZ were examined for the ability to cause nephrotoxicity in mice pretreated with BSO. 4-Methyl- and 4-phenylthiazoles were highly effective compounds. In the absence of BSO, 4-methylthiazole resulted in no nephrotoxicity; inhibitors of hepatic and renal cytochrome P-450 enzymes such as methoxsalen and piperonyl butoxide prevented the nephrotoxicity of 4-methylthiazole given in combination with BSO. In addition, there was a sex difference in the nephrotoxicity of 4-methylthiazole in combination with BSO; the nephrotoxicity was observed only in males. These features of nephrotoxicity of 4-methylthiazole are well in accord with those of TBZ previously reported. This suggests that TBZ and 4-methylthiazole share a common mechanism of nephrotoxicity.
 ...
PMID:Nephrotoxicity of thiazoles structurally related to thiabendazole in mice depleted of glutathione by treatment with buthionine sulfoximine. 162 24

The present study was carried out to elucidate the mechanism by which the permeable thiol drug diethyldithiocarbamate (DEDC) exhibited an antidotal effect against acetaminophen-induced hepatotoxicity in vivo. DEDC was found to act as an antidote against acetaminophen-induced cytotoxicity in hepatocytes isolated from a pyrazole-pretreated rat without affecting cytochrome P-450 levels. The mechanism of protection exhibited against reactive intermediate N-acetyl-p-benzoquinoneimine (NAPQI)-induced cytotoxicity by DEDC was then investigated and compared with that exhibited by the permeable thiol-reductant dithiothreitol (DTT). Cytotoxicity induced by the dimethylated analogue 2,6-dimethyl-N-acetyl-p-benzoquinoneimine (2,6-diMeNAPQI) was prevented if the hepatocytes were preincubated with DEDC for 5 min and removed before addition of 2,6-diMeNAPQI. Both DEDC and DTT were also found to act as antidotes against NAPQI- and 2,6-diMeNAPQI-induced cytotoxicity in isolated rat hepatocytes if added within 2 min of the addition of the quinoneimines. However, the addition of DEDC or DTT 10 min after either quinoneimine did not prevent subsequent cytotoxicity or restore GSH levels, indicating that the alkylation of GSH and of protein thiols was irreversible at that time. Fast atom bombardment mass spectrometry was used to show that DEDC formed conjugates with both NAPQI and 2,6-diMeNAPQI. Furthermore, these conjugates were found to be nontoxic. This suggests that DEDC acts as a trap for the toxic quinoneimines, thus preventing alkylation of essential macromolecules. In contrast, DTT reduced the quinoneimines to their respective nontoxic parent compounds and presumably also reduced mixed-protein disulfides and GSSG, thereby regenerating protein thiols and GSH. Therefore, this study suggests that DEDC and DTT act as antidotes by two different mechanisms.
 ...
PMID:Molecular mechanism for prevention of N-acetyl-p-benzoquinoneimine cytotoxicity by the permeable thiol drugs diethyldithiocarbamate and dithiothreitol. 164 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>