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

Oxidative stress due to excessive reactive species (RS) and weakened antioxidant defenses is causally associated with inflammation and inflammatory mediators. To investigate the effects of the major fish oil ingredients, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on oxidative stress-related inflammatory status, we conducted in vitro experiments utilizing rat renal epithelial cells (NRK-52E) and murine macrophages (RAW 264.7) by assessing their effects on the generation of cyclooxygenase (COX)-2-derived and xanthine oxidase (XOD)-derived RS, reduced glutathione (GSH) levels, and antioxidative enzyme activities. Additionally, 6-keto-prostaglandin (PG) F1alpha, PGE2, and nitrite levels were measured in lipopolysaccharide-stimulated RAW 264.7 macrophages. Results showed that the generation of RS from arachidonic acid through the COX-2 and XOD pathways was effectively suppressed by DHA and EPA, while GSH levels and antioxidative enzyme activities were significantly enhanced by DHA and EPA. Furthermore, levels of inflammatory mediators (thromboxane B2, PGE2, and 6-keto-PGF1alpha) and nitrite were effectively down-regulated by DHA and EPA. These results strongly indicate that DHA and EPA exert antioxidative and anti-inflammatory actions by reducing the cellular levels of RS, pro-inflammatory mediators, and nitrite levels and by maintaining higher GSH levels and antioxidative enzyme activities.
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PMID:Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages. 1765 Oct 56

Oxidant-mediated injury plays an important role in the pathophysiology of inflammatory bowel disease (IBD). Recently, antioxidants were shown to modulate colitis in mice. In this study, the protective effects of L-cysteine and glutathione (GSH) prodrugs are further evaluated against progression of colitis in a murine model. ICR mice were fed compounds incorporated into chow as follows: Group (A) received chow supplemented with vehicle. Group (B) was provided 2-(RS)-n-propylthiazolidine-4(R)-carboxylic-acid (PTCA), a cysteine prodrug. Group (C) received D-ribose-L-cysteine (RibCys), another cysteine prodrug that releases L-cysteine. Group (D) was fed L-cysteine-glutathione mixed sulfide (CySSG), a ubiquitous GSH derivative present in mammalian cells. After 3 days, the animals were further provided with normal drinking water or water supplemented with dextran sodium sulfate (DSS). Mice administered DSS developed severe colitis and suffered weight loss. Colonic lesions significantly improved in animals treated with PTCA and RibCys and, to a lesser extent, with CySSG therapy. Hepatic GSH levels were depleted in colitis animals (control vs DSS, P < 0.001), and normalized with prodrug therapies (control vs treatments, P > 0.05). Protein expressions of serum amyloid A and inflammatory cytokines [interleukin (IL)-6, IL-12, tumor necrosis factor-alpha (TNF-alpha), osteopontin (OPN)] were significantly increased in colitis animals and improved with therapies. Immunohistochemistry and Western blot analyses showed significant upregulation of the macrophage-specific markers, COX-2 and CD68, which suggests macrophage activation and infiltration in the colonic lamina propria in colitis animals. These abnormalities were attenuated in prodrug-treated mice. In conclusion, these data strongly support the novel action of the PTCA against colitis, which further supports a possible therapeutic application for IBD patients.
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PMID:Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model. 1765 32

The major pathobiological mechanisms of IR injury include excitotoxicity, oxidative stress, and inflammation. TF3, a major constituent of black tea, possesses biological functions such as anti-oxidative and anti-inflammatory activities. The purpose of this study was to verify the neuronal protective potential of TF3 and its mechanisms against cerebral IR injury in rats. TF3 administration (10 and 20 mg.kg-1) ameliorated the infarct volume. TF3 also decreased the content of MDA and NO. TF3 significantly increased the activity of SOD and GSH-Px, which were reduced by IR injury. Administration of TF3 decreased mRNA and protein expression of COX-2 and iNOS. DNA binding and Western blotting revealed an increase in NF-kappaB activation and IkappaB depletion in IR brain tissue. Pretreatment with TF3 markedly inhibited IRinduced increase in nuclear localization of NF-kappaB, and preserved IkappaB in the cytoplasm. The results show that TF3 exerts protective effects against cerebral IR injury by reducing oxidative stress and modulating the NF-kappaB activation.
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PMID:Modulation of the oxidative stress and nuclear factor kappaB activation by theaflavin 3,3'-gallate in the rats exposed to cerebral ischemia-reperfusion. 1797 6

Depletion of glutathione levels and perturbations in redox status are considered to play a crucial role in aging and chronic inflammatory processes through the activation of redox sensitive transcription factors, including nuclear factor-kappaB (NF-kappaB). In the current study, we assessed the regulatory action of dietary betaine in the suppression of NF-kappaB by comparing kidney tissue from old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months) and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the molecular assessment of betaine's restorative ability of redox status when treating cells with potent glutathione (GSH)-depleting agents. Results showed that in old rats a short-term feeding (10 d) with betaine attenuated the age-related decrease in thiol levels, increase in reactive species and TNFalpha expression via NF-kappaB activation, compared to the young controls. These findings were verified in the cell-cultured system. Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaB activation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment. Based on both in vivo and in vitro data, we concluded that betaine exerts its efficacy by maintaining thiol status in the regulation of COX-2 and TNFalpha via NF-kappaB activation during aging.
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PMID:Betaine modulates age-related NF-kappaB by thiol-enhancing action. 1805 6

Chitosan oligosaccharide (COS, 3 kDa<MW<5 kDa) was tested for colon cancer chemoprevention by measuring the activities of quinine reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, ornithine decarboxylase (ODC) activity, and cyclooxygenase (COX)-2 expression in HT-29 cells treated with COS. COS induced QR activity in a dose-dependent manner over a concentration range of 0.1-4.0 mg/ml. GST activity was also induced in HT-29 cells treated with COS. In addition, GSH levels were increased 1.3-, 1.4-, and 1.5-fold with COS at 2, 3, and 4 mg/ml, respectively. ODC activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by 33% and 39% with 3 and 4 mg/ml of COS, respectively. COS also inhibited the expression of TPA-induced COX-2 protein in HT-29 cells. These results suggest that COS has colon cancer chemopreventive activity by increasing QR and GST activities and GSH levels and by inhibiting ODC activity and COX-2 expression in vitro.
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PMID:Chemopreventive effect of chitosan oligosaccharide against colon carcinogenesis. 1806 35

Intracerebral hemorrhage (ICH) is a devastating neurological injury associated with significant mortality. Astrocytic inflammation may contribute to the pathogenesis of ICH, although the underlying cellular mechanisms remain unclear. In this study, the hemoglobin oxidation by-product, hemin, concentration dependently induced necroptotic cell death in cortical astrocytes within 5 h of treatment. Hemin-induced cell death was preceded by increased inflammatory gene expression (COX-2, IL-1beta, TNF-alpha, iNOS). Inhibition of the NF-kappaB transcription factor reversed inflammatory gene expression and attenuated cell death after hemin treatment, suggesting a possible role for inflammatory mediators in astrocytic injury. Superoxide production paralleled the increase in iNOS expression, and inhibition of either iNOS (aminoguanidine or iminopiperdine) or superoxide (apocynin) significantly reduced cell death. Similarly, reduced formation of peroxynitrite, the damaging product of nitric oxide and superoxide, significantly reduced hemin injury. Hemin-induced peroxidative injury was associated with a rapid depletion of intracellular glutathione (GSH), culminating in lipid peroxidation and cell death, effects that were reduced by cotreatment with exogenous GSH, N-acetyl-L-cysteine, or the glutathione peroxidase mimetic ebselen. Together, these studies suggest a novel role for GSH depletion in necroptotic astrocyte injury after a hemorrhagic injury and indicate that therapeutic targeting of GSH may exert a beneficial effect after ICH.
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PMID:Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes. 1870 98

Oxidative stress and inflammatory responses induced by silica nanoparticles were evaluated both in mice and in RAW264.7 cell line. Single treatment of silica nanoparticles (50mg/kg, i.p.) led to the activation of peritoneal macrophages, the increased blood level of IL-1beta and TNF-alpha, and the increased level of nitric oxide released from the peritoneal macrophages. mRNA expressions of inflammation-related genes such as IL-1, IL-6, TNF-alpha, iNOS, and COX-2 were also elevated in the cultured peritoneal macrophages harvested from the treated mice. When the viability of splenocytes from the mice treated with silica nanoparticles (50mg/kg, 100mg/kg, and 250mg/kg, i.p.) was measured, the viability of splenocytes was significantly decreased in the higher dose-treated groups (100mg/kg, 200mg/kg i.p.). However, cell proliferation without cytotoxicity was shown in group treated with relatively low dose of 50mg/kg i.p. When leukocyte subtypes of mouse spleen were evaluated using flow cytometry analysis, it was found that the distributions of NK cells and T cells were increased to 184.8% and 115.1% of control, respectively, while that of B cells was decreased to 87.7%. To elucidate the pro-inflammatory mechanism of silica nanoparticles in vivo, in vitro study using RAW 264.7 cell line which is derived from mouse peritoneal macrophage was done. Treatment of silica nanoparticles to the cultured RAW264.7 cells led to the reactive oxygen species (ROS) generation with a decreased intracellular GSH. In accordance with ROS generation, silica nanoparticles increased the level of nitric oxide released from the cultured macrophage cell line. These results suggested that silica nanoparticles generate ROS and the generated ROS may trigger the pro-inflammatory responses both in vivo and in vitro.
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PMID:Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. 1902 59

The exposure of manganese is believed to be the risk of respiratory diseases. COX-2 is a protein involved in biosynthesis of inflammatory prostaglandins. Evidence suggests that COX-2 involves in the pathogenesis of lung inflammation. In this study, the effect of manganese-chloride (manganese) on COX-2 expression in A549 human lung epithelial cells was investigated. Treatment with manganese induced COX-2 at both protein and mRNA levels that were due to COX-2 transcriptional activation. Interestingly, manganese treatment led to activation of ERKs, p38 MAPK, JNKs, ATF-2, and PKB, but not NF-kappaB, and also cellular GSH depletion in A549 cells. Importantly, the manganese-induced COX-2 expression was suppressed by treatment with the inhibitor of p38 MAPK (SB203580), PI3K/PKB (LY294002), PKCs (GO6983, GF109203X, Rottlerin), Src (PP1), or the thiol-containing compound (NAC). There was crosstalk between p38 MAPK and GSH depletion or Src in response to manganese signal. Induction of COX-2 by manganese was also seen in different human airway cells, including H292 (bronchial) or Hep2 (laryngeal). These results collectively suggest that manganese induces COX-2 by transcriptional up-regulation in human airway cells and the induction appears to be cooperatively mediated via multiple signaling pathways and GSH depletion.
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PMID:Induction of COX-2 in human airway cells by manganese: role of PI3K/PKB, p38 MAPK, PKCs, Src, and glutathione depletion. 1908 89

The bromobenzene (BB)-induced hepatotoxicity comes from its reactive metabolites. The efficacy of different doses of ginger (Zingiber officinalesRose) extract in alleviating hepatotoxicity was investigated in male albino rats. Oxidative stress parameters were monitored. The drugs metabolizing enzymes; cytochrome P450 and GST, pro-inflammatory marker; COX-2 and the apoptotic marker; caspase-3 were assessed. Animals were assigned to 1 of 5 groups: control group; bromobenzene (460 mg/kg BW) alone, three animal groups 3-5 treated with different doses of ethanolic ginger extract (100, 200, 300 mg/kg BW, respectively) 2 weeks prior bromobenzene (460 mg/kg BW) treatment. Rats received orally ginger extract daily for 21 days whereas bromobenzene treatment for 7 days starting from 15th day of treatment. Oral treatment of BB was found to elicit a significant decrease in the activities of the antioxidant enzymes; SOD, GPx and the GSH level, while the activities of GR and drug metabolizing enzymes; GSTs and Cyt P450 were enhanced. Also, BB-treatment resulted in a great enhanced production of nitric oxide products and activation of COX-2 and caspase-3. Pre-treatment with different doses of ginger extract prior to BB-treatment alleviated its toxic effects on the tested parameters in the three animal groups.
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PMID:Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats. 1937 70

We examined the effects of polysaccharides extracted from Asterina pectinifera on the activities of quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase (ODC), cyclooxygenase (COX)-2 and glutathione (GSH) levels in HT-29 human colon adenocarcinoma cells. We found that the polysaccharides extract induced QR activity in a dose-dependent manner over a concentration range of 20 approximately 60 microg/ml and increased GST activity as much as 1.4-fold over controls. GSH levels were increased 1.3- and 1.5-fold with the extract at 40 and 60 microg/ml, respectively. The activity and protein expression of ODC in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colon cancer cells was inhibited by the extract. The polysaccharides suppressed TPA-induced prostaglandin (PG) production. These data indicate that polysaccharides from A. pectinifera increase phase II detoxification enzyme activity and inhibit ODC and COX-2 activities in HT-29 human colon adenocarcinoma cells. Consequently, this effect may contribute to the protective effect of polysaccharides from A. pectinifera against colon cancer.
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PMID:Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells. 1947 Feb 41


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