Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncosuppressive effect of melatonin on 9,10-dimethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S-transferase (GST) when compared with the corresponding controls, along with a significant drop in hepatic microsomal contents of cytochromes b5 and P450. This induction of GSH and GST, and depletion of cytochromes b5 and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model.
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PMID:A possible modulatory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9,10-dimethyl-1,2-benzanthracene induced rat mammary tumorigenesis. 128 33

Melatonin, the chief hormone secreted by the pineal gland, has been previously shown to inhibit human breast cancer cell growth at the physiological concentration of 1 nM in vitro. In this study, using the estrogen receptor (ER)-positive human breast tumor cell line MCF-7, we have shown that 10 microM L-buthionine-[S,R]-sulfoximine (L-BSO), an inhibitor of gamma-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis), blocks the oncostatic action of 1 nM melatonin over a 5-day incubation, indicating that glutathione is required for melatonin action. The result was repeated with ZR75-1 cells, suggesting that the glutathione requirement is a general phenomenon among ER+ breast cancer cells. Addition of exogenous glutathione (1 microM) to L-BSO-treated groups restored the melatonin response in both cell lines. Further demonstration of the importance of glutathione was shown using the ER- breast tumor cell line HS578T, which is normally unresponsive to melatonin. Growth in this cell line was inhibited in the presence of 1 microM ethacrynic acid (an inhibitor of glutathione S-transferase) plus 1 nM melatonin, and this effect was blocked with 10 microM L-BSO. We also observed a steady decrease of intracellular glutathione in MCF-7 cells over a 5-day incubation, suggesting that these cells metabolize glutathione differently than do normal cells.
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PMID:Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway. 915 84

We have previously reported that exposures of F344 male rats to both 900 MHz and 1.5 GHz electro-magnetic near fields (EMFs) results in slightly decreased numbers and areas of glutathione S-transferase (GST-P)-positive liver foci, liver preneoplastic lesions in rats, in a medium-term liver bioassay (K. Imaida, M. Taki, T. Yamaguchi, T. Ito, S. Watanabe, K. Wake, A. Aimoto, Y. Kamimura, N. Ito, T. Shirai, Lack of promoting effects of the electromagnetic near-field used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay, Carcinogenesis 19 (1998) 311-314; K. Imaida, M. Taki, S. Watanabe, Y. Kamimura, T. Ito, T. Yamaguchi, N. Ito, T. Shirai, The 1.5 GHz electromagnetic near-field used for cellular phones does not promote rat liver carcinogenesis in a medium-term liver bioassay, Jpn. J. Cancer Res. 89 (1998) 995-1002.). In both experiments, the melatonin serum levels were significantly decreased in both 900 MHz and 1.5 GHz exposed groups as compared with sham-exposed control group values. Therefore, changes of serum melatonin levels may modify the development of preneoplastic lesions in the livers of rats exposed by EMF. In order to clarify this question, the effects of different doses of melatonin (1, 5, 10 and 20 ppm in the drinking water) were analyzed in the same bioassay system employed for our previously reported EMF exposure studies. Six-week-old male F344 rats were given a single dose of diethylnitrosamine (DEN, 200 mg/kg b.w., i.p.). Starting 2 weeks later, they were treated with 0, 1, 5, 10 and 20 ppm melatonin in their drinking water for 6 weeks. Melatonin treatment were performed only during the night (between 18:00 to 09:00) in order to maintain their circadian rhythm, since serum melatonin levels are high at midnight. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At week 8, the experiment was terminated and the animals were sacrificed. Serum hormone levels of melatonin, adrenocorticotropic hormone (ACTH), corticosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone at this time point were measured, only the first being elevated, while LH and testosterone were reduced. Although clear dose dependence was not apparent, both numbers and areas of GST-P-positive foci in the liver were decreased in the melatonin treated groups, this being significant for numbers in the 10 ppm melatonin group. Comparison of the current results with the previously reported findings for EMF exposure experiments, suggests that increase in melatonin serum levels is a possible reason for the associated tendency for decreased preneoplastic hepatocyte foci development.
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PMID:Inhibitory effects of low doses of melatonin on induction of preneoplastic liver lesions in a medium-term liver bioassay in F344 rats: relation to the influence of electromagnetic near field exposure. 1081 86

The goals of this study were to analyze the renal oxidative status in experimental biliary obstruction and to evaluate the impact of melatonin on renal oxidative stress. Cholestasis was done by double ligature and section of the extra-hepatic biliary duct. Melatonin was injected i.p. (500 microg/kg/day). Malondialdehyde, reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione transferase were determined in the renal tissue. After biliary obstruction, an increase in malondialdehyde (P<0.0001) and a fall in reduced glutathione (P<0.0001) were seen. Moreover, the scavenger enzyme activity had significantly diminished. After melatonin administration, the malondialdehyde fell significantly (P<0.0001), whereas reduced glutathione showed an important increase (P<0.0001) compared with the ligated bile duct group. Experimental bile duct obstruction was associated to an increase of renal oxidative stress. Treatment with melatonin decreased the renal lipid peroxidation, and both the reduced glutathione as well as the scavenger enzyme activity recovered.
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PMID:Melatonin protects against renal oxidative stress after obstructive jaundice in rats. 1150 79

Recently, numerous studies have shown antioxidant actions of melatonin. Melatonin at both physiological and pharmacological levels stimulates glutathione peroxidase, glutathione reductase and superoxide dismutase activities in the brains of rats and chickens. This study was designed to evaluate the effect of melatonin on nephropathy and oxidative stress under constant light exposure. Nephropathy was induced by adriamycin administered in a single dose (25 mg kg(-1) b.w., i.p.). Melatonin was injected i.p. (1,000 microg kg(-1) b.w./day). Malondialdehyde, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione transferase, catalase and superoxide dismutase were determined in kidney. Urea, creatinine and total proteins in plasma and proteinuria were evaluated and melatonin was determined. Results show a decrease in melatonin levels. Similar effects occurred with the antioxidant enzyme activities and reduced glutathione. Likewise, adriamycin and constant light induced significant enhancement of malondialdehyde. All changes induced both by adriamycin and constant light were reverted to normal by melatonin administration. Constant light exposure was associated with an increase in oxidative stress and nephropathy induced by adriamycin. Treatment with melatonin decreased lipid peroxides, and permitted a recovery of reduced glutathione, scavenger enzyme activity and parameters of renal function.
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PMID:Melatonin effect on renal oxidative stress under constant light exposure. 1257 19

We examined the effect of melatonin in prooxidant and antioxidant state in the liver of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed with normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months without and with melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase malondialdehyde (MDA) and diene conjugate (DC) levels in the liver. This diet lowered glutathione (GSH), alpha-tocopherol, and total ascorbic acid levels as well as glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver, but hepatic superoxide dismutase (SOD) activity remained unchanged. Although melatonin treatment did not affect these parameters in mice fed a normal diet, it reduced hepatic MDA and DC levels in mice fed an HC diet. Hepatic alpha-tocopherol and ascorbic acid levels increased, but hepatic GSH levels remained unchanged in the melatonin-treated HC group as compared to the HC group. Melatonin treatment was found to increase liver GSH-Px and GST activities in mice fed an HC diet. However, SOD activity did not alter in the liver of hypercholesterolemic mice following melatonin treatment. In addition, the histopathological lesions observed in the cholesterol-plus-melatonin group were less severe than those seen in the cholesterol group. According to these observations, we can say that melatonin treatment has an ameliorating effect on the disturbances in prooxidant and antioxidant balance and histopathological lesions in the liver of mice following cholesterol feeding.
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PMID:Melatonin improved the disturbances in hepatic prooxidant and antioxidant balance and hepatotoxicity induced by a high cholesterol diet in C57BL/6J mice. 1562 73

It has been suggested that oxidative stress is a feature of aging. The goal of the present study was to assess the oxidant effects related to aging and the protective role of exogenous melatonin in senescence-accelerated mice (SAMP8). Two groups of SAMP8 mice (males and females) were compared with their respective control groups of SAMR1 mice (senescence-resistant inbred strain) to determine their oxidative status without melatonin treatment. Four other groups of the same characteristics were treated with melatonin (10 mg/kg/day) in their drinking water. The melatonin concentration in the feeding bottles was titrated according to water consumption and body weight (i.e. 0.06 mg/mL for 30 g of body weight and 5 mL/day of water consumption). The treatment began when animals were 1-month old and continued for 9 months. When mice were 10-month old, they were anesthetized and blood was obtained. Plasma and erythrocytes were processed to examine oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), and hemolysis. The results showed greater oxidative stress in SAMP8 than in SAMR1, largely because of a decrease in GSH levels and to an increase in GSSG and TBARS with the subsequent induction of the antioxidant enzymes GPX and GR. Melatonin, as an antioxidant molecule, improved the glutathione-related parameters, prevented the induction of GPX in senescent groups, and promoted a decrease in SOD and TBARS in almost all the groups.
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PMID:Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice. 1687 20

The disturbances in pro- and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu-Zn superoxide dismutase (SOD-1), catalase, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD-1, GSH-Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD-1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age-related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age-related diseases and to prolong the lifespan and improve the quality of life of elderly people.
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PMID:Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects. 1728 47

In two previous communications to the RANM four and two years ago, some data were shown supporting the role of GH, Melatonin and Estrogens in the prevention of aging in a group of physiological parameters including bone, liver metabolism and vascular activity, the Central nervous System (CNS,) the immune system and the skin. In the present work data about the molecular mechanisms involved will be presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and Melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and Melatonin and the second with these two and additionally with Estradiol and Phytosoya. Aging was associated with a reduction in the number of neurones of the Hylus of the dentate gyrus of the hypothalamus and with a reduction of neurogenesis. GH treatment increased the number of neurones but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases. Melatonin, estrogens and phytosoya treatments increased neurogenesis but did not enhanced the total number of neurones. On the liver, aging induced a signi-ficant increase in mitochondrial nitric oxide, an increase in cytochrome C in the cytosolic fraction and a reduction in the mitochondrial fraction thus inducing apoptosis as confirmed by the increase in caspases. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly reduce the enhanced and increase the reduced values reducing apoptosis. A reduction in glutathione peroxidase and glutathione S-transferase was found also in old control rats when compared with the group of young animals. Keratinocytes from old rats in culture showed an increase in nucleosomes and a reduction in Bcl2 that was restored with GH and Melatonin. In conclusion, the mentioned hormonal treatment seems to have beneficial effects against age-induced damage in the CNS the liver and the skin through molecular mechanisms reducing oxidative stress and apoptosis.
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PMID:[Molecular mechanisms of aging and its prevention by hormonal treatment in rats]. 1745 Oct 99

N-nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was assessed in liver and erythrocyte fraction of NDEA-treated rats. NDEA administration inhibited body weight, macro- and microscopically detectable liver tumors and increased levels of plasma AST, ALT and alpha-fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA-treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.
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PMID:Prevention by melatonin of hepatocarcinogenesis in rats injected with N-nitrosodiethylamine. 1780 29


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