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)

1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 microliters/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.
Gen Pharmacol 1994 Jan
PMID:Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain. 802 20

1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a typical pattern of aminoglycoside nephrotoxicity characterized histopathologically by necrosis of proximal tubular epithelium, and biochemically by increased serum creatinine and urea concentrations. Reduced glutathione (GSH) concentration in renal cortex was significantly decreased by gentamicin. 2. Simultaneous treatment of rats with gentamicin and either captopril or diltiazem significantly potentiated the gentamicin-induced increases in serum creatinine and urea and did not significantly affect the gentamicin-induced decrease in cortical GSH concentration. 3. Concomitant treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly affect serum creatinine concentration, and significantly increased cortical GSH concentration in comparison to the values of these parameters following gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced renal damage was exacerbated by captopril, and even more so by diltiazem. Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate produced only mild focal atrophy of renal tubular epithelium. Control rats had apparently normal histology. 5. In conclusion, captopril and diltiazem, at the doses used, significantly potentiated gentamicin-induced nephrotoxicity to a broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses used, reduced significantly the severity of some of the manifestations of nephrotoxicity, they were equally ineffective in completely preventing the development of nephrotoxicity.
Gen Pharmacol 1993 Sep
PMID:Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat. 827 Jan 87

1. An experimental comparative study on isolated guinea pig lungs was carried out to determine the effect of selenium added to pulmoplegic solution on ischemic lung preservation. 2. Two different types of solutions (Eurocollins in control group and Eurocollins + selenium 10(-3) M in experimental group) were infused before 3 hr of normothermic ischemia. 3. Tissue malone dialdehyde (MDA) and tissue glutathione (GSH) levels were assessed before the ischemic period, after the ischemia and at the end of reperfusion. Electron microscopic changes were also studied at the end of reperfusion to compare the cellular injury between the groups. 4. Addition of selenium before the ischemic period relatively decreased tissue MDA levels after reperfusion but did not alter tissue GSH levels.
Gen Pharmacol 1995 Dec
PMID:Effect of selenium on ischemic and reperfusion injury in isolated guinea pig lungs. 874 54

Since modulation of the glutathione (GSH) level has been implicated in the regulation of human immunodeficiency virus (HIV) transcription and expression, we have undertaken an analysis of the effect of sodium valproate (VPA) on HIV-1 replication. VPA, which is an anti-epileptic drug in widespread use in clinical medicine, has been shown to depress the activity of GSH reductase, an enzyme required for maintaining high cellular levels of reduced GSH. The effect of this drug on HIV-1 replication has been studied in primary infected cells, i.e. peripheral blood mononuclear cells (PBMC) and monocyte/macrophages, in the CEM-SS cell line, and in chronically infected stimulated and non-stimulated U1 cells. We have shown that VPA markedly enhanced viral replication in all infected cells tested. Virus production was induced in U1 cells by VPA treatment and the stimulatory effects of tumour necrosis factor-alpha, interleukin-6 and granulocyte/macrophage colony-stimulating factor were augmented. The LTR-driven gene expression in Jurkat T cells was increased. However, the elevated viral production did not correlate with the effect of VPA on the intracellular GSH level. Thus, VPA stimulated in vitro HIV-1 replication in acutely and chronically infected cells and enhanced LTR-driven gene expression. These effects were observed for concentrations that are reached in the plasma of VPA-treated patients. Therefore, although the clinical significance of these data remains to be demonstrated, these results should be considered in the choice of an anticonvulsant drug in HIV-infected individuals.
J Gen Virol 1996 Sep
PMID:Sodium valproate, an anticonvulsant drug, stimulates human immunodeficiency virus type 1 replication independently of glutathione levels. 881 Sep 95

The effect of administration of superoxide dismutase (SOD) on gentamicin nephrotoxicity was examined in rats. SOD was administered at a dose of 2000 i.u/kg or 8000 i.u/kg for 10 consecutive days, and nephrotoxicity was induced by daily i.m. injections of gentamicin at a dose of 80 mg/kg during the last 6 days of the experimental period. Gentamicin induced significant increases in plasma creatinine and urea and protein urinary concentrations, and significant decreases in creatinine clearance and kidney cortical alkaline phosphatase activity and reduced glutathione (GSH) concentrations. The antibiotic also produced marked necrosis of the renal proximal tubules. SOD treatment (8000 i.u/kg) reversed most of these variables, indicating that it was effective in ameliorating gentamicin nephrotoxicity. However, at a dose of 2000 i.u./kg it was mostly ineffective.
Gen Pharmacol 1996 Mar
PMID:Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. 891 55

1. Multidrug resistance (MDR) is a phenomenon originally seen in cultured tumor cells that, following selection for resistance to a single anticancer agent, become resistant to a range of chemically diverse anticancer agents. These MDR cells show a decrease in intracellular drug accumulation due to active efflux by transporter proteins. The transporter best characterized is P-glycoprotein (Pgp). This protein has been identified in many cancers and has been the target for agents able to inhibit its action, thereby reversing resistance. 2. More recently, another transporter, multidrug resistance-associated protein (MRP) has been identified in a number of MDR human tumor cell lines that do not apparently express Pgp. The presence of MRP at the cell surface of these cells is associated with alterations in drug accumulation and distribution. 3. The gene-encoding MRP has been cloned and sequenced and shown by transfection studies to be able to confer resistance and changes in drug accumulation in sensitive tumor cells. The profile of anticancer drugs expelled in the presence of MRP is similar, but not identical, to that of Pgp. 4. MRP has been identified in a number of different types of cancers, but it is not yet clear to what extent it is involved with clinical resistance. Furthermore, resistance modulators useful against Pgp are less effective in reversing MRP-mediated resistance. 5. It is not fully understood how MRP brings about drug efflux, but it is clear that the underlying mechanisms are different from those responsible for Pgp-mediated drug efflux. In particular, glutathione (GSH) is required for the effective expulsion of the anticancer agents. 6. Unlike Pgp, MRP is able to transport metallic oxyanions and glutathione and other conjugates, including peptidyl leukotrienes. Agents that inhibit organic anion transport, such as probenecid, can block MRP activity. 7. Like Pgp, MRP is expressed not only in resistant tumor cells, but also in normal human tissues. These include the epithelial cells lining the airways and the gastrointestinal tract. In cells in normal tissues, MRP appears to be located within the cytoplasm, which may mean that it functions here in a manner slightly different to that in malignant cells. It is now also recognized in cells and tissues from other species, such as the rat and mouse.
Gen Pharmacol 1997 May
PMID:Multidrug resistance-associated protein: a protein distinct from P-glycoprotein involved in cytotoxic drug expulsion. 918 95

The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca(2+)-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, beta-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2'-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibition by oxidation persisted following washout of the compounds, but the effects of reduction were reversed by subsequent oxidation, and vice versa. The thiol-specific reagents N-ethylmaleimide and (2-aminoethyl)methanethiosulfonate inhibited channel activity and prevented the effect of subsequent sulfhydryl oxidation. Measurements of macroscopic currents in inside-out patches indicate that reduction only shifted the voltage/nP0 relationship without an effect on the maximum conductance of the patch, suggesting that the increase in nP0 following reduction did not result from recruitment of more functional channels but rather from changes of channel gating. We conclude that redox modulation of cysteine thiol groups, which probably involves thiol/disulfide exchange, alters maxi-K channel gating, and that this modulation likely affects channel activity under physiological conditions.
J Gen Physiol 1997 Jul
PMID:Redox regulation of large conductance Ca(2+)-activated K+ channels in smooth muscle cells. 923 69

1. The effect of fish oil administration by gavage (0.4% body weight) on activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) and on content of thiobarbituric acid reactive substances (TBARs) of the lymphoid organs [thymus, spleen and mesenteric lymph nodes (MLN)] and liver was investigated in 21-day pregnant rats. The results were compared with those obtained by administration of soybean oil, cocoa butter and coconut oil. 2. Oil administration did not have any significant effect on antioxidant enzyme activities of the liver, whereas marked changes were found in the lymphoid organs. The MLN presented the most pronounced changes: SOD and catalase activities were increased by the four oils; GSH-Px activity was raised by soybean and fish oils; coconut oil reduced the activity of the three antioxidant enzymes in this organ. 3. Fish oil given by gavage does affect the antioxidant capacity of the lymphoid organs; however, similar effect was also observed for cocoa butter and soybean oil. These changes in the antioxidant enzyme activities were able to prevent the lipid peroxidation process in the lymphoid organs.
Gen Pharmacol 1997 Oct
PMID:Changes in the activities of antioxidant enzymes of the lymphoid organs of 21-day pregnant rats due to administration of fish oil by gavage. 935 1

1. The effect of administration of fish oil by gavage on catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities of the lymphoid organs and liver was compared with those of soybean oil and cocoa butter. 2. Fish oil did not affect the activities of SOD and CAT but reduced that of GSH-Px in the spleen. In contrast, cocoa butter reduced the CAT activity in the thymus and liver, and soybean oil decreased CAT activity in the thymus. 3. The content of thiobarbituric acid reactive substances of the lymphoid organs was not modified but was increased in plasma.
Gen Pharmacol 1998 May
PMID:Effect of the administration of fish oil by gavage on activities of antioxidant enzymes of rat lymphoid organs. 955 31

1. The present study determined the effects of Fructus corni extract (FCE) on the levels of hydrogen peroxide (H2O2) and superoxide anion (O2-), on the glutathione (GSH) redox cycle and on the activities of antioxidant enzymes in bovine pulmonary artery endothelial cells (PAECs). 2. Confluent monolayers of PAECs were incubated with FCE, and oxidative stress was triggered by hypoxanthine and xanthine oxidase (to induce H2O2) or H2O2 (to induce O2-). 3. FCE exhibited a concentration-dependent suppression of H2O2 and O2-. 4. It modulated the GSH redox cycle by increasing the intracellular GSH content, the activities of GSH peroxidase and GSH disulfide reductase, and by decreasing the intracellular level of GSH disulfide. 5. It also increased the activities of superoxide dismutase and catalase. 6. These results demonstrate that FCE can promote a protective antioxidant defense state by affecting some important enzymatic and nonenzymatic oxidant-scavenging systems and may thus be useful for the prevention or treatment of disorders associated with oxidative damage.
Gen Pharmacol 1998 Aug
PMID:Fructus corni enhances endothelial cell antioxidant defenses. 968 63


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