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At least 829 records · Page 46Linked to original sources
PubMed2005

Retinoid X receptor alpha Regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver.

Nuclear receptors, including constitutive androstane receptor, pregnane X receptor, and retinoid X receptor (RXR), modulate acetaminophen (APAP)-induced hepatotoxicity by regulating the expression of phase I cytochrome P450 (P450) genes. It has not been fully resolved, however, whether they regulate APAP detoxification at the phase II level. The aim of the current study was to evaluate the role of RXRalpha in phase II enzyme-mediated detoxification of APAP. Wild-type and hepatocyte-specific RXRalpha knockout mice were treated with a toxic dose of APAP (500 mg/kg i.p.). Mutant mice were protected from APAP-induced hepatotoxicity, even though basal liver glutathione (GSH) levels were significantly lower in mutant mice compared with those of wild-type mice. High-performance liquid chromatography analysis of APAP metabolites revealed significantly greater levels of APAP-GSH conjugates in livers and bile of mutant mice compared with those of wild-type mice. Furthermore, hepatocyte RXRalpha deficiency altered the gene expression profile of the glutathione S-transferase (Gst) family. Basal expression of 13 of 15 Gst genes studied was altered in hepatocyte-specific RXRalpha-deficient mice. This probably led to enhanced APAP-GSH conjugation and reduced accumulation of N-acetyl-p-benzoquinone imine, a toxic electrophile that is produced by biotransformation of APAP by phase I P450 enzymes. In conclusion, the data presented in this study define an RXRalpha-Gst regulatory network that controls APAP-GSH conjugation. This report reveals a potential novel strategy to enhance the detoxification of APAP or other xenobiotics by manipulating Gst activity through RXRalpha-mediated pathways.

Acetaminophen↗
PubMed1975

Liver glutathione and glutathione reductase response of endotoxin-treated mice.

The decrease in the level of liver glutathione (GSH) in endotoxin-treated mice was in part due to formation of glutathione disulfide (GSSG). An electron-generating system (EGS) had no effect when incubated with soluble liver extracts from normal controls but resulted in recovery of GSH amounting to 25% in endotoxin-treated animals. Incubation in the absence of the EGS caused a decline of 16% in the GSH in extracts from normal animals compared with a 50% decrease in endotoxin-treated animals. Exclusion of nicotinamide adenine dinucleotide phosphate (NADP) from the EGS resulted in a slight decline in the GSH of the extract from the normal controls but 25% for the endotoxin-treated animals. Reduction of exogenous GSSG by the liver extracts required that exogenous NADP be added to ghe incubation mixtures.

Animals↗
PubMed1999

Purification of a glutathione S-transferase and a glutathione conjugate-specific dehydrogenase involved in isoprene metabolism in Rhodococcus sp. strain AD45.

A glutathione S-transferase (GST) with activity toward 1, 2-epoxy-2-methyl-3-butene (isoprene monoxide) and cis-1, 2-dichloroepoxyethane was purified from the isoprene-utilizing bacterium Rhodococcus sp. strain AD45. The homodimeric enzyme (two subunits of 27 kDa each) catalyzed the glutathione (GSH)-dependent ring opening of various epoxides. At 5 mM GSH, the enzyme followed Michaelis-Menten kinetics for isoprene monoxide and cis-1, 2-dichloroepoxyethane, with Vmax values of 66 and 2.4 micromol min-1 mg of protein-1 and Km values of 0.3 and 0.1 mM for isoprene monoxide and cis-1,2-dichloroepoxyethane, respectively. Activities increased linearly with the GSH concentration up to 25 mM. 1H nuclear magnetic resonance spectroscopy showed that the product of GSH conjugation to isoprene monoxide was 1-hydroxy-2-glutathionyl-2-methyl-3-butene (HGMB). Thus, nucleophilic attack of GSH occurred on the tertiary carbon atom of the epoxide ring. HGMB was further converted by an NAD+-dependent dehydrogenase, and this enzyme was also purified from isoprene-grown cells. The homodimeric enzyme (two subunits of 25 kDa each) showed a high activity for HGMB, whereas simple primary and secondary alcohols were not oxidized. The enzyme catalyzed the sequential oxidation of the alcohol function to the corresponding aldehyde and carboxylic acid and followed Michaelis-Menten kinetics with respect to NAD+ and HGMB. The results suggest that the initial steps in isoprene metabolism are a monooxygenase-catalyzed conversion to isoprene monoxide, a GST-catalyzed conjugation to HGMB, and a dehydrogenase-catalyzed two-step oxidation to 2-glutathionyl-2-methyl-3-butenoic acid.

Amino Acid Sequence↗
PubMed1993

Decreased glutathione content and glutathione S-transferase activity in red blood cells of coal miners with early stages of pneumoconiosis.

Blood samples of miners heavily exposed to coal dust were examined for changes in glutathione S-transferase (GST) activity. Decreased GST activity was found in red blood cells of subjects with early stages of coal workers' pneumoconiosis (International Labour Office classification 0/1-1/2) when compared with control miners. At further progression of coal workers' pneumoconiosis (> or = 2/1), the activity of GST was not different from controls. In the same group with moderate coal workers' pneumoconiosis a decrease in GSH in red blood cells occurred. Decreases in GST activity in early stages of coal workers' pneumoconiosis, as well as the decreases in glutathione peroxidase (GPx) activity and in GSH concentrations reported earlier, may originate from damage caused by reactive oxygen species. These changes might imply an impairment of the detoxification capacity for electrophilic and oxidative compounds during this stage of the disease.

Coal Mining↗
PubMedDate not supplied

Changes in tissue levels of glutathione, extent of lipid peroxidation, and activity of glutathione peroxidase in transplantable murine lymphoma.

The reduced glutathione (GSH) levels in the hepatic tissues, extent of lipid peroxidation in the liver, kidney and brain, and alterations in the activity of glutathione peroxidase (GPX) in the hepatic tissues were monitored in mice bearing a transplantable ascitic lymphoma. These markers showed substantial alterations during the height of tumour progression when compared to controls. The GSH level, extent of lipid peroxidation, and GPX activity increased sharply after approximately 2 weeks following inoculation of ascitic cells. This was followed by a steady decline in all markers and death occurred around day 32 after inoculation.

Animals↗
PubMed2005

Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria.

BACKGROUND: High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria. METHODS: Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects. RESULTS: MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P < 0.0001, P < 0.0001; GSH: P < 0.0001, P < 0.0001; GPx: P < 0.0001, P < 0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria (P < 0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria (P < 0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients (P > 0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria (P < 0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients (r = 0.549, P < 0.0001; r = -0.385, P<0.01). CONCLUSION: Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.

Adult↗
PubMed2004

Activity of glutathione peroxidase, glutathione reductase, and lipid peroxidation in erythrocytes in workers exposed to lead.

The aim of this study was to estimate the activity of glutathione peroxidase (GPx), glutathione reductase (GR), and malondialdehyde (MDA) in erythrocytes in healthy male employees of zinc and lead steelworks who were occupationally exposed to lead over a long period of time (about 15 yr). Workers were divided into two subgroups: the first included employees with low exposure to lead (LL) (n=75) with blood lead level PbB=25-40 microg/dL and the second with high exposure to lead (HL) (n=62) with PbB over 40 microg/dL. Administration workers (n=35) with normal levels of PbB and zinc protoporphyrin in blood (ZPP) in blood were the control group. The activity of GPx significantly increased in LL when compared to the control group (p<0.001) and decreased when compared to the HL group (p=0.036). There were no significant changes in activity of GR in the study population. MDA erythrocyte concentration significantly increased in the HL group compared to the control (p=0.014) and to the LL group (p=0.024). For the people with low exposure to lead (PbB=25-40 microg/dL), the increase of activity of GPx by about 79% in erythrocytes prevented lipid peroxidation and it appears to be the adaptive mechanism against the toxic effect of lead. People with high exposure to lead (with PbB over 40 microg/dL) have shown an increase in MDA concentration in erythrocytes by about 91%, which seems to have resulted from reduced activity of GPx and the lack of increase in activity of GR in blood red cells.

Adult↗
PubMed1996

S-(1,2- dicarboxyethyl)glutathione and glutathione in lens and liver of napthalene-treated rabbits.

The determination of S-(1,2-dicarboxyethyl)glutathione and reduced glutathione (GSH) in the rabbit lens and liver was developed using an isotachophoretic analyser. The recovery of S-(1, 2-dicarboxyethyl)GSH from the rabbit liver after ion-exchange treatment was 96.8 +/- 11.3% (n=3). The contents of S-(1,2-dicarboxyethyl)GSH in the rabbit lens and liver were 219.9 +/- 29.1 (n=5) and 44.0 +/- 13.5 (n = 8) nmol/g, respectively. The contents of S-(1, 2-dicarboxyethyl)GSH in the lens and GSH in the lens and liver of naphthalene-treated rabbits was also determined by this method 24 hours after naphthalene administration, at which time the axial opacity "spichen" was observed at the equatorial region of the lens. The content of S-(1,2-dicarboxyethyl)GSH in the lens decreased in proportion to the content of GSH. During the further development of true lens opacity after naphthalene administration, the S-(l, 2-dicarboxyethyl)GSH content further compared with that in the spichen stage, but the S-(1, 2-dicarboxyethyl)GSH content of the lens that did not develop true opacity after naphthalene administration returned to the normal level. The change of S-(1, 2-dicarboxyethyl)GSH content of the lens in the spichen and true opacity stages coincided with that of GSH content. On the other hand, the content of GSH of the liver decreased markedly until 24 hours after naphthalene administration, then returned to normal, irrespective of whether true opacity did or did not subsequently develop.

Animals↗
PubMed2000

Erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children with valproate and carbamazepine monotherapy.

This prospective study was carried out to determine changes in the antioxidant system in epileptic children receiving long term antiepileptic drugs (AEDs). Levels of erythrocyte glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and serum lipid peroxidation were determined in 25 healthy children and 30 epileptic children who had not yet received AEDs. Sixteen patients were treated with valproic acid (VPA) and 14 with carbamazepine (CBZ); 13 months later these parameters were retested. The results showed that SOD and lipid peroxidation levels were increased but the GSH-Px levels were decreased in epileptic children on VPA therapy compared with the control group and the results before treatment. No significant differences of these parameters were found in epileptic children on CBZ therapy compared with the control group and the results before treatment, except that lipid peroxidation level was slightly higher in epileptic patients before treatment. We conclude that antioxidant systems in epileptic children on CBZ therapy are better regulated in comparison with epileptic children on VPA therapy.

Adolescent↗
PubMed1998

Effects of mild chronic heat exposure on the concentrations of thiobarbituric acid reactive substances, glutathione, and selenium, and glutathione peroxidase activity in the mouse liver.

To determine whether mild and chronic heat stress leads to oxidative stress and to differentiate such effects of different exposure periods, we kept male ICR-mice at an ambient temperature of either 35 degrees C or 25 degrees C for 6 hours, 3 days, or 7 days and measured the concentrations of thiobarbituric acid reactive substances (TBARS), glutathione (GSH), selenium (Se), and glutathione peroxidase (GSH-Px) activities in the liver. Since the food consumption of the heat-exposed group was only half that of the control, we prepared pair-fed groups, which were kept at 25 degrees C and whose food consumption were limited to those of the heat-exposed group for the 3-day and the 7-day exposure. TBARS concentrations of the liver was significantly higher in the heat group than the control after the 3-day exposure, while there was no significant difference among the groups after the 7-day exposure. There was no significant difference in GSH concentrations between the heat-exposed group and the control after the 7-day exposure, when the GSH concentration of the pair-fed group was significantly lower than that of the control. Hepatic cytosolic Se GSH-Px activity in the heat group was significantly less than that in the control group after the 6-hour exposure and it tended to be lower in the heat group than that of the control group after the 7-day exposure, while there was no difference in the total GSH-Px activity among the three groups. Our results showed that mild and chronic heat exposure may cause oxidative damage to organisms and that GSH-related anti-oxidative systems would play an important role to defensive reaction.

Animals↗
PubMed1984

Glutathione peroxidase, glutathione reductase and superoxide dismutase in the aging lens.

Glutathione reductase (GR) and glutathione peroxidase (GPx) show in bovine lenses a decrease in specific activity; furthermore, the heat lability of both enzymes increases with age monitoring structural changes of the molecules. GR activity was correlated with type of cataract in human lenses. Its decrease is significantly connected with cortical opacities. Superoxide dismutase activity declines in aging and cataractous lenses. These results support the assumption that in old lens tissue the capacity of the antioxidative scavanger system is diminished.

Adult↗
PubMed1991

Phospholipid hydroperoxide glutathione peroxidase is a selenoenzyme distinct from the classical glutathione peroxidase as evident from cDNA and amino acid sequencing.

The primary structure of phospholipid hydroperoxide glutathione peroxidase (PHGPx) was partially elucidated by sequencing peptides obtained by cyanogen bromide cleavage and tryptic digestion and by isolating and sequencing corresponding cDNA fragments covering about 75% of the total sequence. Based on these data PHGPx can be rated as a selenoprotein homologous, but poorly related to classical glutathione peroxidase (GPx). Peptide loops constituting the active site in GPx are, however, strongly conserved in PHGPx. This suggests that the mechanism of action involving an oxidation/reduction cycle of a selenocysteine residue is essentially identical in PHGPx and GPx.

Amino Acid Sequence↗
PubMed2001

Glutathione and glutathione S-transferases as early markers for ovarian carcinomas: case series.

AIM: To determine the activity of glutathione (GSH) and concentrations of glutathione S-transferases (GST), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1), and to evaluate their diagnostic and prognostic value and possible correlation with clinical and histopathological prognostic factors for ovarian carcinomas. METHODS: The concentrations of GSH, uPA, PAI-1, and activity of GST were analyzed in 35 tissue samples taken from 10 normal ovaries, 10 benign, 10 primary malignant, and 5 metastatic ovarian tumors. The GSH level and GST activity were determined by spectrophotometric methods, and uPA and PAI-1 concentrations by ELISA commercial kits. RESULTS: GSH concentrations were significantly higher in primary malignant (126.3+/-12.8 nmol/mg protein) and metastatic (160.5+/-24.3 nmol/mg protein) ovarian tumor specimens than in normal ovarian tissue (48.9+/-8.1 nmol/mg protein, p<0.003 for both carcinoma groups) or benign ovarian tumor samples (35.2+/-5.0 nmol/mg protein, p=0.001). The GST activity was significantly higher in primary malignant (245.8+/-22.7 nmol/min/mg protein) and metastatic (303.7+/-48.8 nmol/min/mg protein) ovarian tumor tissues than in benign tumor specimens (105.9+/-16.2 nmol/min/mg protein, p<0.004 for both carcinoma groups) or normal ovarian tissue samples (133.2+/-32.0 nmol/min/mg protein, p<0.044 for both carcinoma groups). There were no statistical differences in uPA and PAI-1 concentrations between normal, benign, and malignant tumor samples. Concentrations of GSH, uPA and PAI-1, and activity of GST were independent from histopathological and clinical prognostic factors. CONCLUSION: Increased GSH concentration and GST activity found in primary malignant and metastatic ovarian tumor samples were independent of histopathological and clinical prognostic factors, suggesting that they could be early markers for ovarian carcinomas.

Analysis of Variance↗
PubMed2001

[Activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and superoxide dismutase in the brain tumors].

The aim of the study was to estimate the activity of glutathione peroxydase, glutathione reductase and superoxide dysmutase in the brain tumours. The activity of GSH-Px was evaluated with the use of spectrophotometry, GSSG-R was evaluated based on the Mize and Langdon method, and SOD-1 with Sykes et al. method. The 55 specimens (45 specimens of neoplasm and 10 specimens of healthy brain tissue) were studied. The statistical analysis revealed significant increase of enzymes within the brain tumours in comparison to the healthy brain tissue.

Brain Neoplasms↗
PubMed2002

[Activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and superoxide dismutase (SOD-1) in single brain metastasis].

The aim of the study was to evaluate the activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and superoxide dysmutase (SOD-1) in the single brain metastases. The activity of the GSH-Px was evaluated with the use of spectrophotometry, GSSG-R was evaluated basing on the method of Mize and Langdon and SOD-1 with Sykes et al. method. The examinations were carried out in 36 specimens (10 specimens of healthy brain tissue, 12 specimens of brain metastases, 14 specimens of glioma multiforme). The statistical analysis revealed significant increase (p < 0.001) of GSH-Px and GSSG-R activity within the single brain metastases in comparison with the healthy brain tissue.

Brain Neoplasms↗
PubMed1992

The relationship between reduced glutathione level and glutathione S-transferase activity in sheep erythrocytes.

The relationship between reduced glutathione (GSH) level and glutathione S-transferase (GST) activity in erythrocytes was examined, using sheep erythrocytes, which have varying GSH concentrations, and dog erythrocytes with an inherited high concentration of GSH. There was a positive correlation (r = 0.529, p < 0.001) between the GSH level and GST activity in sheep erythrocytes. In dog erythrocytes, the GST activity in high-GSH cells was significantly (p < 0.001) higher than that in normal-GSH cells. These results indicate that the activity of GST in erythrocytes is directly correlated with the intracellular GSH level.

Animals↗
PubMed1992

[Quantitative analysis of glutathione and glutathione S-transferase in human brain tumors, C6 rat glioma cells and drug resistant C6 cells].

Glutathione (GSH) and Glutathione S-transferase (GST) plays an important role in the protection of cells against damage from free radicals and also influences cytotoxicity to some kinds of chemotherapeutic agents. GST comprises a group of abundant and widely distributed catalytic and binding proteins that facilitate the conjugation of GSH with the electrophilic center of a large spectrum of hydrophilic molecules. Multiple GST isozymes in mammalian tissues arise from dimeric combination of a number of distinct subunits grouped into three major classes: alpha (alpha), mu (mu), and pi (p). We report the total GST, GST-p activity and GSH content of human brain tumors, C6 rat glioma cells and drug resistant C6 cells. The values of total GST activity in 42 normal brain and brain tumors were quantitatively analyzed. Total GST activity was 92.6 +/- 25.1 units (mean +/- standard deviation) in 8 samples of normal brain tissues, 126 +/- 58.8 units in five grade II or III astrocytomas (154 +/- 63.3 units in grade II astrocytomas, 84.4 +/- 2.7 units in 2 grade III astrocytoma), 66.2 +/- 29.3 in 5 glioblastoma cases, 94.7 +/- 47.7 units in 3 metastatic tumors, 302 +/- 114 unit in 8 meningiomas and 213 +/- 90.4 units in 3 neurinomas. Differences of GST activity between glioblastomas and meningiomas, grade II or III astrocytomas and meningioma, in normal brain tissues and meningioma were statistically significant (p < 0.01). The difference between normal brain tissues and benign tumors (meningiomas and neurinomas), gliomas and benign tumors were also statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗