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1.
da Rosa EJ da Silva MH Carvalho NR Bridi JC da Rocha JB Carbajo-Pescador S Mauriz JL González-Gallego J Soares FA 《Toxicologic pathology》2012,40(4):605-613
In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure. 相似文献
2.
Oxidative stress and changes in liver antioxidant enzymes induced by experimental dicroceliosis in hamsters 总被引:1,自引:0,他引:1
S. Sánchez-Campos M. J. Tuñón P. González J. González-Gallego 《Parasitology research》1999,85(6):468-474
The purpose of our study was to assess the effects of experimental dicroceliosis on the antioxidant defense capability of
the liver in hamsters. Studies were carried out at 80 and 120 days after infection with an oral dose of 40 metacercariae of
Dicrocoelium dendriticum. The parasitic pathology was ascertained by the presence of fluke eggs in feces, increased serum ALT and AST activities,
and histological findings. The concentration of thiobarbituric acid-reactive substances (TBARS) and the ratio of oxidized
to reduced glutathione (GSSG/GSH), measured as markers of oxidative stress, were significantly increased [TBARS: +40% and
+84% at 80 and 120 days postinfection (p.i.), respectively; GSSG/GSH: +200% and +117%]. Dicroceliosis increased Se-dependent
glutathione peroxidase (GPx) activity in both cytosol (+24% and +46%) and mitochondria (+73% and +41%). Superoxide dismutase
activity was significantly reduced in cytosol (−19% and −38%) and mitochondria (−20% and −39%). No significant change was
found in the activity of Se-independent GPx or catalase. The ratio of glutathione peroxidase/glutathione reductase at 80 and
120 days p.i. was increased by 25% and 63%, respectively. Gamma-glutamyl cysteinyl synthetase activity was increased by 27%
and 20%, respectively. Our data indicate that although dicroceliosis courses with activation of antioxidant enzymes and glutathione
synthesis, inefficient scavenging of reactive oxygen species takes place, resulting in oxidative liver damage.
Received: 1 November 1998 / Accepted: 17 December 1998 相似文献
3.
Luís Fernando Deresz Cinthia Maria Schöler Paulo Ivo Homem Júnior de Bittencourt Marlus Karsten Maria Letícia Rodrigues Ikeda Anelise Sonza 《HIV clinical trials》2018,19(4):152-157
Background: Exercise training has been shown to be an effective strategy to balance oxidative stress status; however, this is underexplored in people living with HIV/AIDS (PLWHA). Objective: To evaluate the effects of exercise training on oxidative stress in PLWHA receiving antiretroviral therapy. Methods: Patients performed 24 sessions (3 times per week, 8 weeks) of either aerobic (AT), resistance (RT), or concurrent training (CT). Glutathione disulphide to glutathione ratio (GSSG/GSH) in circulating erythrocytes and thiobarbituric acid–reactive substances (TBARS) in plasma samples were assessed as oxidative stress markers. Eight PLWAH completed the training protocol (AT =3, RT =3, CT =2). The GSSG/GSH and TBARS values were logarithmically transformed to approximate a normal distribution. A paired t-test was used to determine the differences between baseline and post-training values. Results: Data-pooled analysis showed a decrease in GSSG/GSH and TBARS after the training period: log GSSG/GSH= –1.26?±?0.57 versus –1.54?±?0.65, p?=?.01 and log TBARS =0.73?±?0.35 versus 0.43?±?0.21, p?=?.01. This was paralleled by a rise in peak oxygen uptake (VO2peak?=?29.14?±?5.34 versus 32.48?±?5.75?ml kg?1 min?1, p?=?.04). All the subjects who performed resistance exercises showed an average gain of 37?±?8% in muscle strength with no difference between performing single or multiple sets in terms of muscle strength gain. The results reinforce the clinical importance of exercise as a rehabilitation intervention for PLWHA and emphasizes the safety of exercise at the physiological level with the potential to mediate health outcomes. 相似文献
4.
Stephane Palazzetti Marie-Jeanne Richard Alain Favier Irene Margaritis 《Revue canadienne de physiologie appliquée》2003,28(4):588-604
We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study. 相似文献
5.
Trimetazidine improved Ca2+ handling in isoprenaline-mediated myocardial injury of rats 总被引:1,自引:0,他引:1
Dysregulation of intracellular Ca2+ homeostasis plays an important role in mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve intracellular Ca2+ handling in myocardial injury of rats. The control group received saline only (10 ml kg(-1) day(-1), i.p.) for 7 days. In a second group, isoprenaline (ISO; 5 mg kg(-1) day(-1), s.c.) was administered to rats for 2 days to induce an acute injury of the myocardium. In a third group, treatment with TMZ (10 mg kg(-1) day(-1), i.p.) was initiated 1 day before ISO administration and continued for 7 days (n = 7 rats in each group). Histopathological evaluation showed that TMZ prevented ISO-induced myocardial damage. TMZ preserved the ATP levels and decreased the maleic dialdehyde (MDA) content in the hearts compared with ISO-treated rats. The diastolic [Ca2+]i measured by loading with fura-2 AM in isolated cardiomyocytes was increased significantly in ISO-treated rats compared to the control animals. TMZ prevented the rise of diastolic [Ca2+]i and the depression of caffeine-induced Ca2+ transients caused by ISO administration. The reduction in sarcoplasmic reticulum (SR) Ca2+ content in the heart cells and in cardiac SR Ca2+-ATPase activity in ISO-treated rats was abolished by TMZ, although there were no differences in SR Ca2+-ATPase protein levels between the control, ISO and ISO + 7 mz-treated rats. In addition, TMZ prevented the reduction in sarcolemmal L-type Ca2+ current density in the heart cells induced by ISO treatment. These results demonstrate that the treatment of rats with TMZ inhibited the increase of diastolic [Ca2+]i and prevented the decrease of SR Ca2+ content, SR Ca2+-ATPase activity and L-type Ca2+ current density in cardiomyocytes in ISO-mediated myocardial injury of rats. These changes in Ca2+ handling could help to explain the favourable action of TMZ in myocardial injury. 相似文献
6.
Marina Prendes MG Hermann R Torresin ME Souto P Tallis S Savino EA Varela A 《The journal of physiological sciences : JPS》2011,61(4):303-312
The effects of ischemic-postconditioning (IPOC) on functional recovery and cell viability of ischemic-reperfused hearts from
fed and fasted rats were studied in relation to triacylglycerol and glycogen mobilization, ATP content, glucose-6-phosphate
dehydrogenase activity and reduced/oxidized glutathione (GSH/GSSG). Oxidative damage was estimated by measuring thiobarbituric
acid reactive substances (TBARS). IPOC improved contractile recovery and cell viability in the fed but attenuated them in
the fasted hearts. In both groups ischemia lowered glycogen. IPOC further reduced it. Triacylglycerol remained unchanged during
ischemia-reperfusion in both groups, but triacylglycerol mobilization was activated by IPOC in the fasted group. ATP was increased
by IPOC in the fed hearts, but lowered in the fasted ones, which appeared to be associated with the rates of ATP synthesis
in isolated mitochondria. In the fed hearts IPOC raised glucose-6-phosphate dehydrogenase activity and GSH/GSSG, and lowered
TBARS. These results suggest that IPOC effects are associated with changes in the ATP supply, mobilization of energy sources
and glutathione antioxidant ratio. 相似文献
7.
Sandhya N Gokulakrishnan K Ravikumar R Mohan V Balasubramanyam M 《Disease markers》2010,29(5):213-221
Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation
to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes.
Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance
(NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM
with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were
measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD.
Results: T2DM subjects with NAFLD had significantly (p < 0.001) higher levels of thiobarbituric acid reactive substances
(TBARS) and protein carbonyls (PCO) but lower (p < 0.001) GSH/GSSG ratio and adiponectin levels compared to other three
groups. The association of hypoadiponectinemia withNAFLD/Type 2 diabetes was significant even after adjusting for age, gender
and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio
in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated
cells.
Conclusion: There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM.
In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin. 相似文献
8.
Eplerenone reduces oxidative stress and enhances eNOS in SHR: vascular functional and structural consequences 总被引:2,自引:0,他引:2
Sanz-Rosa D Oubiña MP Cediel E De las Heras N Aragoncillo P Balfagón G Cachofeiro V Lahera V 《Antioxidants & redox signaling》2005,7(9-10):1294-1301
The aim of the present study was to evaluate the effect of the aldosterone receptor antagonist eplerenone on endothelial function, oxidative stress, and structural alterations present in spontaneously hypertensive rats (SHR). To carry out the study, male SHR (18 weeks old) were treated with two doses of eplerenone (30 and 100 mg/kg/day) for 10 weeks. A group of n = 8 untreated SHR was used as a control-vehicle group, and a group of Wistar Kyoto rats (n = 8) was used as a reference of normotensive conditions. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Endothelium-dependent and -independent relaxations, as well as endothelial nitric oxide synthase (eNOS) and the subunit p22phox of NAD(P)H oxidase mRNA expressions, were studied in aorta from SHR untreated or treated with eplerenone. Media/lumen ratio was also calculated in aortic preparations. In addition, levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and malonyl dialdehyde (MDA) were evaluated in liver homogenates. Treatment with eplerenone reduced (p < 0.05) SAP and normalized aortic media/lumen ratio and acetylcholine relaxations. Both doses of the drug enhanced (p < 0.05) eNOS and reduced p22phox mRNA expressions. Similarly, eplerenone increased (p < 0.05) hepatic GSH/GSSG ratio, and reduced (p < 0.05) hepatic MDA levels in a comparable manner. Consequently, it could be concluded that aldosterone participates in the functional and structural vascular alterations of SHR through the diminution of nitric oxide availability and an enhancement of vascular and systemic oxidative stress. 相似文献
9.
Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH) redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG) through glutathione peroxidase (GPx), and converted back to GSH by glutathione reductase (GR). Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities. 相似文献
10.
The reduced form of glutathione (GSH; gamma-glutamyl cysteinyl glycine) is supposedly the most powerful reducing battery in the central nervous system against oxidative stress. We evaluated the contribution of GSH and GSSG to MEGA-PRESS (a frequency-selective refocusing technique) signals assessed by magnetic resonance spectroscopy (MRS). GSH gave a single positive signal (2.95 ppm) by the MEGA-PRESS. In contrast, GSSG gave a multiplet of reversed signals (3.03, 3.23, and 3.34 ppm). A phantom solution mimicking the normal in vivo condition (GSH:GSSG=100:1) gave a single positive peak. Even when the ratio was changed to 10:1, corresponding to toxic oxidative stress, GSH was prominent and GSSG signals were minimal. Thus, GSSG signals could be negligible. In the phantom solution (creatine:GSH:aspartate:gamma-aminobutyric acid=7:3:1:1), the creatine signal overshadowed the other signals. Through the MEGA-PRESS, a single peak of GSH stood out over other signals. In vivo, the brains of healthy volunteers gave similar signals as the in vitro phantom solution, indicating that the signal originated from GSH. The estimated concentration of GSH in the human brain was 1.9+/-0.37 mM (mean+/-S.D., n=4). In conclusion, MEGA-PRESS allowed us to assess GSH levels in vivo non-invasively. 相似文献
11.
T. Gedrange A. Lupp B. Walter W. Harzer R. Bauer 《Experimental and toxicologic pathology》2001,53(1):89-96
Stress due to endurance training of striated muscles leads to adaptive changes in the distribution of muscle fiber types (i.e. ratio of type I and type II fibers). Moreover, severe training leads to tissue hypoxia and oxidative stress in muscles. In the current study, we examined the relationship between histological changes and oxidative state in muscles of mastication during the acute adaptation phase to a sustained muscle load. Six domestic pigs received build-ups on the molar teeth in order to induce a sustained load of the muscles of mastication for a duration of four weeks. Afterwards the masseter (M1, M2, M3), medial pterygoid (PM), temporal (TP1, TP2), and geniohyoid muscles (GH) were removed and the fiber type distribution was determined by enzyme histochemistry. Additionally, the tissue content of glutathione and lipid peroxidation (LPO) products were measured. The above treatment led to muscle fiber transformation of type II into type I (M1, M2, TP2, PM) and a decrease of the GSH content (M1, M2 and TP2). The changes in the GSH/GSSG ratio were in accordance with the changes in proportions of muscle fiber types, with the lowest GSH/GSSG ratios in the most stressed muscles of the treated animals. No significant changes in LPO products were found. The decrease of the GSH/GSSG ratio in the most stressed muscles indicates an increased intracellular oxidative stress, which may be caused by tissue hypoxia during the chronic phase of muscle adaptation. 相似文献
12.
Beier J Beeh KM Semmler D Buhl R 《International archives of allergy and immunology》2004,135(1):30-35
BACKGROUND: The pathogenesis of late asthmatic reactions after allergen challenge in contrast to isolated early responses is incompletely understood. Recently, the antioxidant glutathione and endogenous nitrosothiols were shown to protect against bronchoconstriction. We compared reduced (GSH) and oxidized glutathione (GSSG) and nitrosothiols in induced sputum following allergen challenge in mild asthmatics with isolated early (EAR) and dual early and late (LAR) asthmatic responses. METHODS: Exhaled nitric oxide, sputum cells and sputum supernatant concentrations of GSH, GSSG and nitrosothiols were quantified 2-5 days prior to and 24 h after allergen challenge in 24 mild asthmatics (12 EAR, 12 LAR, only beta-agonists prn). RESULTS: There were no differences at baseline between EAR and LAR asthmatics for any of the parameters (p > 0.1, all comparisons). Mean +/- SD fall in forced expiratory volume in 1 s, expressed as the percentage decrease compared to the baseline value, between 3 and 8 h after allergen challenge was 1 +/- 5% in the group of patients without LAR vs. 24.9 +/- 8.7% in the group of patients with LAR (p < 0.001). Sputum eosinophils increased in both groups (p < 0.05, both comparisons), whereas neutrophils only increased in LAR subjects (p = 0.06 vs. EAR). In contrast, GSH was significantly increased 24 h after challenge only in EAR asthmatics [geometric mean with 95% confidence intervals: before: 3.3 microM (1.25-7.9 microM), after: 5.9 microM (2.7-12.9 microM), p = 0.05; mean difference vs. LAR subjects: 6 microM (0.1-12 microM), p = 0.048], and the proportion of GSSG was positively correlated with postallergen eosinophils in all patients (rho = 0.4, p = 0.05). There was no change in nitrosothiols after 24 h in either EAR or LAR subjects (p > 0.23, all comparisons). CONCLUSIONS: GSH increases 24 h after allergen challenge in isolated early responders. These data suggest that different adoptive responses to allergen may result in different physiologic phenotypes. Further studies on the role of glutathione in allergen-induced bronchoconstriction are clearly warranted. 相似文献
13.
B. J. Shenker C. Rooney L. Vitale J. S. Mayro I. M. Shapiro 《Immunopharmacology and immunotoxicology》1993,15(2):273-290
The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione2 (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes. Whether a decrease in GSH or a change in the thiol redox state causes functional deficits associated with low level mercury exposure remains to be determined. 相似文献
14.
DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of gliomas. Despite their frequent use, the therapeutic efficacy of these agents is limited by the development of resistance. Previous studies suggest that the mechanism of this resistance is complex and involves multiple DNA repair pathways. To better define the pathways contributing to the mechanisms underlying glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose- and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci formation, both hallmarks of FA pathway activation. The FA-deficient cells were more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To test whether these observations were pertinent to glioma biology, we screened a panel of glioma cell lines and identified one (HT16) that was deficient in the FA repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA pathway activation by a small molecule inhibitor (curcumin) or by small interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87 glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive to that of methyl-guanine methyl transferase inhibition. The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance. 相似文献
15.
G Braikow S Braekow-Bruzzi R Gl?ckner R Graf 《Experimental and toxicologic pathology》1992,44(5):287-293
Treatment of pregnant rats with heat-denaturated bacterial material (endotoxin-model) or exposure to chronic restraint of prenatally lithium-treated pregnant dams (stress-model) were used as two models of disturbed pregnancy, both causing decreased fetal body mass. The quotient of fetal/placental mass was lowered in the endotoxin-group only. Placental mass and protein content were not changed significantly in both experimental groups, although a tendency to smaller placentae was noticed in the stress-group. Placental histology of the stress-group did not differ from untreated controls. In the endotoxin-group an altered structure of the placental barrier was observed. Small decreases of GSH and GSSG in the endotoxin-group and of GSSG in the stress-group without significant changes of the GSH/GSSG relationship were measured in homogenates of the placental labyrinth. Moderate enhancement of LPO concentration occurred in the endotoxin-group and more distinctly in two litters of the stress-group, the latter being connected with high GSSG concentrations and low fetal/placental mass-quotients. 相似文献
16.
Utsugi M Dobashi K Koga Y Shimizu Y Ishizuka T Iizuka K Hamuro J Nakazawa T Mori M 《Journal of leukocyte biology》2002,71(2):339-347
We examined whether changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione of human monocytes regulate lipopolysaccharide (LPS)-induced IL-12 production and defined the molecular mechanism that underlies glutathione redox regulation. Monocytes exposed to glutathione reduced form ethyl ester (GSH-OEt) or maleic acid diethyl ester (DEM) increased or decreased the intracellular GSH/GSSG ratio, respectively. LPS-induced IL-12 production and p38 mitogen-activated protein (MAP) kinase activation were enhanced by GSH-OEt but suppressed by DEM. Selective p38 inhibitors showed that p38 promoted GSH-OEt-enhanced IL-12 production. Furthermore, IFN-gamma priming increased the GSH/GSSG ratio and enhanced IL-12 production through p38, and DEM negated the priming effect of IFN-gamma on p38 activation and IL-12 production as well as on the GSH/GSSG ratio. These findings reveal that glutathione redox regulates LPS-induced IL-12 production from monocytes through p38 MAP kinase activation and that the priming effect of IFN-gamma on IL-12 production is partly a result of the glutathione redox balance. 相似文献
17.
Correia S Carvalho C Santos MS Proença T Nunes E Duarte AI Monteiro P Seiça R Oliveira CR Moreira PI 《Medicinal chemistry (Shāriqah (United Arab Emirates))》2008,4(4):358-364
We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H(2)O(2)) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H(2)O(2) are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent. 相似文献
18.
Donahue AN Aschner M Lash LH Syversen T Sonntag WE 《Mechanisms of ageing and development》2006,127(1):57-63
Systemic growth hormone (GH) and insulin-like growth factor-1 (IGF-1), potent anabolic hormones, decrease with age. In humans and animal models, administration of growth hormone or IGF-1 to aged subjects improves learning and memory, suggesting that the age-related decline in cognitive performance results, in part, from peripheral GH/IGF-1 deficiency. However, the cellular mechanisms by which GH/IGF-1 effect cognitive function are unknown. We propose that the effects of these hormones may be mediated by increasing cellular redox potential resulting in reduced oxidative stress. Because the most abundant endogenous antioxidant is glutathione (GSH), we assessed GSH and disulfide glutathione (GSSH) levels in hippocampus and frontal cortex of young (4-month-old) and aged (30-month-old) male Fisher 344xBrown Norway rats treated with porcine growth hormone (200microg/animal, twice/daily) or vehicle. We report that hippocampal levels of GSSG increase with age (0.54+/-0.08 to 1.55+/-0.24nmolGSSG/mgprotein, p<0.05) and growth hormone treatment ameliorates both the age-related rise in GSSG (1.55+/-0.24 to 0.87+/-0.24nmolGSSG/mgprotein, p<0.05) and the decline in GSH/GSSG ratios. Analysis of GSSG reductase activity in aged animals indicated no effect of either age or growth hormone treatment (p=0.81). Although similar age-related increases in GSSG and decreases in GSH/GSSG ratios were evident in frontal cortex, growth hormone had no effect. Subsequently, we assessed whether the effects of age and growth hormone treatment result from modulating trace metal accumulation. Thirteen metals were analyzed in hippocampus and frontal cortex by inductive coupled plasma mass spectrometry. Aluminum, copper, iron, manganese and zinc levels increased with age (p<0.05 each) but growth hormone replacement had no effect on metal accumulation. Our results indicate that growth hormone replacement attenuates the age-related increase in oxidative stress in hippocampus without effects on glutathione reductase or trace metal accumulation. We conclude that the age-related decline in circulating growth hormone and IGF-1 contribute to increased oxidative stress in hippocampus with age. 相似文献
19.
OBJECTIVES: This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen. METHODS: Thirty women who had undergone hysterectomy+bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion. RESULTS: At the sixth month, a higher TAO activity (p=0.016) and a lower eTBARS (p=0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly (p=0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS (p=0.007), LDL TBARS (p=0.044) and eCAT (p=0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu2+ induced ox-LDLTBARS of QQ subjects (p=0.018 and 0.050) as well as LDL TBARS of QR subjects (p=0.044) showed a significant decrease with estrogen-only treatment. CONCLUSIONS: Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies. 相似文献