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Antioxidant Glutathione (antioxidant + glutathione)
Selected AbstractsUnderstanding cisplatin resistance using cellular modelsIUBMB LIFE, Issue 11 2007Britta Stordal Abstract Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 ,g/ml. Cisplatin resistance in these cells correlated with increases in the antioxidant glutathione, yet treatment with buthionine sulphoximine, an inhibitor of glutathione synthesis, had no effect on resistance, suggesting that the increase in glutathione was not directly involved in cisplatin resistance. Two models were developed from H69 SCLC cells, H69-CP and H69CIS200 using 100 ng/ml or 200 ng/ml cisplatin respectively. Both cell models were 2-4 fold resistant to cisplatin, and have decreased expression of p21 which may increase the cell's ability to progress through the cell cycle in the presence of DNA damage. Both the H69-CP and H69CIS200 cells showed no decrease in cellular cisplatin accumulation. However, the H69-CP cells have increased levels of cellular glutathione and are cross resistant to radiation whereas the H69CIS200 cells have neither of these changes. This suggests that increases in glutathione may contribute to cross-resistance to other drugs and radiation, but not directly to cisplatin resistance. There are multiple resistance mechanisms induced by cisplatin treatment, even in the same cell type. How then should cisplatin-resistant cancers be treated? Cisplatin-resistant cell lines are often more sensitive to another chemotherapeutic drug paclitaxel (H69CIS200), or are able to be sensitized to cisplatin with paclitaxel pre-treatment (H69-CP). The understanding of this sensitization by paclitaxel using cell models of cisplatin resistance will lead to improvements in the clinical treatment of cisplatin resistant tumours. IUBMB Life, 59: 696-699, 2007 [source] Lipid Peroxidation and Antioxidant Activities Involved in Resistance Response against Downy Mildew in Opium PoppyJOURNAL OF PHYTOPATHOLOGY, Issue 2 2010Mukesh K. Dubey Abstract The aim of this study was to observe the lipid peroxidation (LP) of cell membranes and antioxidant systems in response to inoculation of Peronospora arborescens causing downy mildew (DM) in opium poppy. Contents of the LP product, malondialdehyde (MDA) and antioxidant glutathione (GSH) were determined in leaves of two opium poppy genotypes, Pps-1 (highly resistant to DM) and Jawahar-16 (highly susceptible to DM) at different time intervals after inoculation (12 h, 24 h, 48 h and 72 h). The provided GSH content corresponded to that of total non-protein sulfhydryl groups. In leaves of Jawahar-16, a significant decrease in concentration of GSH and a persistent increase in concentration of MDA were recorded after inoculation in comparison to leaves of control plants. The continuous decrease in GSH content contributed to damage of cell membranes leading to disease development in Jawahar-16. On the other hand in a resistant genotype (Pps-1), initially at 12 h after inoculation (hai) the level of GSH was found to be high, but a transient and highly significant decrease in content of GSH and increase in content of MDA was observed at 24 hai in comparison to control plants of same genotype and also in comparison to inoculated plants of susceptible genotype (Jawahar-16). These results indicate that generation of GSH and MDA is negatively correlated during the infection process as found in the case of DM-resistant genotype Pps-1 at 24hai, which also suggests an increased need by the host plant for oxidative stress, required for hypersensitive response mediated defense mechanism. [source] Maternal Alcohol Use During Pregnancy Causes Systemic Oxidation of the Glutathione Redox SystemALCOHOLISM, Issue 1 2010Theresa W. Gauthier Background:, Increased systemic oxidant stress contributes to a variety of maternal complications of pregnancy. Although the antioxidant glutathione (GSH) and its oxidized component glutathione disulfide (GSSG) have been demonstrated to be significantly altered in the adult alcoholic, the effects of maternal alcohol use during pregnancy on oxidant stress in the postpartum female remain under investigation. We hypothesized that maternal alcohol use would increase systemic oxidant stress in the pregnant female, evidenced by an oxidized systemic GSH redox potential. Methods:, As a subset analysis of a larger maternal language study, we evaluated the effects of alcohol consumption during pregnancy on the systemic GSH redox status of the postpartum female. Using an extensive maternal questionnaire, postpartum women where queried regarding their alcohol consumption during pregnancy. Any drinking, the occurrence of drinking >3 drinks/occasion, and heavy drinking of >5 drinks/occasion during pregnancy were noted. Using HPLC, maternal plasma samples were analyzed for GSH, oxidized GSSG and the redox potential of the GSH/GSSG antioxidant pair calculated. Results:, Maternal alcohol use occurred in 25% (83/321) of our study sample. Two in ten women reported consuming >3 drinks/occasion during pregnancy, while 1 in 10 women reported consuming alcohol at >5 drinks/occasion. Any alcohol use during pregnancy significantly decreased plasma GSH (p < 0.05), while alcohol at >3 drinks/occasion or >5 drinks/occasion significantly decreased plasma GSH concentration (p < 0.05), increased the percent of oxidized GSSG (p < 0.05), and substantially oxidized the plasma GSH redox potential (p < 0.05). Conclusions:, Alcohol use during pregnancy, particularly at levels >3 drinks/occasion, caused significant oxidation of the systemic GSH system in the postpartum women. The clinical ramifications of the observed alcohol-induced oxidation of the GSH redox system on high risk pregnancies or on the exposed offspring require more accurate identification and further investigation. [source] In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol ExposureALCOHOLISM, Issue 2 2007Xiao-Du Ping Background: The effects of in utero alcohol exposure on the immune function of the newborn remain under investigation. Fetal ethanol (ETOH) exposure increases oxidative stress in the developing lung, in part due to decreased availability of the antioxidant glutathione (GSH). We have previously shown that in utero ETOH impairs alveolar macrophage phagocytosis and viability in the premature pup, while maintaining GSH availability with maternal supplementation of S -adenosyl-methionine (SAM) during ETOH ingestion improves macrophage function and viability. We hypothesized that dysfunction of the neonatal alveolar macrophage exposed to ETOH in utero would persist at term gestation. Methods: Using a guinea-pig model of fetal ETOH exposure, timed-pregnant guinea-pigs were pair-fed ETOH±the GSH precursor SAM and the diet continued until spontaneous delivery. Term alveolar macrophages were evaluated using fluorescent microscopy for phagocytosis and apoptosis after in vitro incubation with Staphalococcus aureus. Using an in vivo model of intranasal Staph. aureus inoculation, the in vivo function of the term alveolar macrophage was also investigated using confocal fluorescent analysis. Results: In utero ETOH exposure increased oxidant stress in the alveolar macrophage and decreased phagocytosis and viability in vitro and in vivo. Confocal analysis of phagocytosis in vivo demonstrated a marked impairment of internalization of the bacteria by the ETOH-exposed alveolar macrophage. The addition of SAM during maternal ETOH ingestion prevented loss of alveolar macrophage function and viability in vitro and in vivo. Conclusions: In utero ETOH exposure impairs alveolar macrophage function and viability in vitro and in vivo even at term gestation. The ETOH-induced changes in macrophage function and viability can be ablated with maternal SAM supplementation. Further investigations are required to identify the mechanisms of ETOH-induced derangement of phagocytosis in the neonatal alveolar macrophage and the clinical ramifications of altered immune function after in utero alcohol exposure for the newborn. [source] Effect of Chronic Ethanol Ingestion on Alveolar Type II Cell: Glutathione and Inflammatory Mediator-Induced ApoptosisALCOHOLISM, Issue 7 2001Lou Ann S. Brown Background : In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome, a syndrome that requires alveolar type II cell proliferation and differentiation for repair of the damaged alveolar epithelium. We previously showed in a rat model that chronic ethanol ingestion decreased the antioxidant glutathione (GSH) in type II cells and exacerbated endotoxin-mediated acute lung injury. We hypothesized that this GSH depletion by ethanol, particularly mitochondrial GSH, predisposed type II cells to inflammatory mediator-induced apoptosis. Methods: Adult male rats were fed the Lieber-DeCarli diet for 2, 6, or 16 weeks. Alveolar type II cells were then isolated and treated with hydrogen peroxide or TNF-,. The effect on glutathione (cytosolic and mitochondrial), apoptotic events, and necrosis were determined. In other studies, rats were fed ethanol for 6 weeks and were treated with endotoxin and apoptosis of type II cells determined by the TUNEL method. Results: Chronic ethanol ingestion alone resulted in a progressive decrease in mitochondrial GSH and a progressive increase in the basal apoptosis and necrosis rate (p, 0.05). Furthermore, there was a progressive increase in the sensitivity of the cells to H2O2 or TNF-, induced cytochrome c release, caspase 3 activation, apoptosis, and necrosis (p, 0.05). Finally, there was a 2-fold increase in apoptotic type II cells in vivo when chronic ethanol ingestion was superimposed on endotoxemia. Conclusions: These results suggested that chronic ethanol ingestion resulted in a progressive depletion of mitochondrial GSH and sensitization of type II cells to inflammatory mediator-induced apoptosis and necrosis. These effects may be particularly relevant during acute stress when proliferation and differentiation of these cells are critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of acute respiratory distress syndrome in patients with a history of alcohol abuse. [source] Nigral glutathione deficiency is not specific for idiopathic Parkinson's diseaseMOVEMENT DISORDERS, Issue 9 2003Paul S. Fitzmaurice PhD Abstract The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [,30%], PSP [,21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [,20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (,19 to ,30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD. © 2003 Movement Disorder Society [source] | |||||||||||||