Protective Effect Of Glutathione Research Articles

GSH Protects the Escherichia coli Cells from High Concentrations of Thymoquinone.

The aim of the present study was to evaluate the potential protective effect of glutathione (GSH) on Escherichia coli cells grown in a high concentration of thymoquinone (TQ). This quinone, as the main active compound of Nigella sativa seed oil, exhibits a wide range of biological activities. At low concentrations, it acts as an antioxidant, and at high concentrations, an antimicrobial agent. Therefore, any interactions between thymoquinone and glutathione are crucial for cellular defense against oxidative stress. In this study, we found that GSH can conjugate with thymoquinone and its derivatives in vitro, and only fivefold excess of GSH was sufficient to completely deplete TQ and its derivatives. We also carried out studies on cultures of GSH-deficient Escherichia coli strains grown on a minimal medium in the presence of different concentrations of TQ. The strains harboring mutations in gene ΔgshA and ΔgshB were about two- and fourfold more sensitive (256 and 128 µg/mL, respectively) than the wild type. It was also revealed that TQ concentration has an influence on reactive oxygen species (ROS) production in E. coli strains—at the same thymoquinone concentration, the level of ROS was higher in GSH-deficient E. coli strains than in wild type.

Protective effects of glutathione on oxidative injury induced by hydrogen peroxide in intestinal epithelial cells

BackgroundReactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species–mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)–induced injury in intestinal epithelial cells. MethodsIEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion. Terminal deoxynucleotidyl transferase–mediated UTP end-labeling staining and cleaved caspase-3 were used to assess apoptosis. The role of P38 mitogen-activated protein kinase (P38 MAPK) signaling was examined using the P38 MAPK agonist U46619 and inhibitor SB203580 in H2O2 and GSH-treated cells. Phosphorylated and total P38 MAPKs and cleaved caspase-3 were measured by Western blot. Data are means ± standard deviation, statistical significance P < 0.05 by student's t-test, or one-way analysis of variance. ResultsPretreatment with GSH attenuates the activation of NF-κB and P38 MAPK signaling pathways by H2O2. GSH also decreased H2O2-mediated increases in interleukin 1 beta secretion, cleaved caspase-3 activation, and apoptosis in IEC-6 cells. SB203580 attenuated the increase in apoptosis and cleaved caspase-3 in H2O2-treated cells. The increase in apoptotic index and cleaved caspase-3 observed in U46619-treated cells was also diminished by GSH. ConclusionsGSH appears to ameliorate oxidative injury in intestinal epithelial cells by attenuating H2O2-mediated activation of NF-κB and P38 MAPK signaling pathways that regulate intestinal inflammation and apoptosis.

Updates on glutathione and capillary bronchitis

Capillary bronchitis is a common respiratory infectious disease.In the early childhood, it is mainly caused by respiratory syncytial virus, which is closely related with later asthma.The pathogenesis is still not entirely clear.Recent studies have found that glutathione functions in keeping airway epithelial integrity, against lung injury and inflammation.This article summarizes the protective effect of glutathione in capillary bronchitis. Key words: Capillary bronchitis; Glutathione; Respiratory syncytial virus

Aluminium oxide nanoparticles-induced spermatotoxicity, oxidative stress and changes in reproductive hormones and testes histopathology in male rats: Possible protective effect of glutathione

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Reversal of Lead-Induced Toxicity Due to the Effect of Antioxidants

This study was designated to evaluate the protective effect of glutathione (GSH) and N-acetyl cysteine (NAC) in reducing the concentration of lead acetate in blood and soft tissues (liver, kidney, and brain) and their ability to restore altered hematopoietic, hepatic, renal, and other biochemical variables that are indicative of tissue oxidative stress in male rats. Male Wistar rats (150 ± 10 g) were randomly divided into 6 groups. Group 1 served as control. Group 2 served as experimental control was administered lead acetate (50 mg/kg intraperitoneally) for 3 days. Group 3 and 4 served as therapeutic controls. Animals in groups 5 and 6 received reduced GSH (1 mg/kg intraperitoneally) and NAC (50 mg/kg orally) for 3 days after the administration of lead acetate, as in group 2. The levels of hepatic and renal markers such as alanine aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, urea, and uric acid were significantly increased (P ≤ 0.05) following administration of lead acetate. Administration of GSH and NAC provided significant protection to thiobarbituric acid reactive substances levels and reduced GSH content in tissues. On the other hand, significant recovery in lead-sensitive biochemical indices, like δ-aminolevulinic acid dehydratase, δ-aminolevulinic acid, and lead concentration in blood and soft tissues also were observed. It was concluded that NAC provided maximum protection compared with reduced GSH.

Protective Effects of Glutathione and Lipoic Acid against Cadmium-Induced Oxidative Stress in Rat’s Kidney

Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney is a major target of Cd-induced toxicity. We analyzed the effects of cadmium exposure on the model system of experimental animals, the thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of xanthine oxidase (XO) and catalase in kidney of rats, with and without glutathione and lipoic acid (LA). The experimental animals were classified into six groups, regarding cadmium, glutathione, and LA intake. The concentration of TBARSs in the homogenate was determined by spectrophotometric method according to Nabavi et al. The specific activity of XO was determined spectrophotometrically by the method of Aygul et al. Catalase activity in tissues was determined by spectrophotometric method according to Nabavi et al. The increased level of TBARS and the increased activity of XO in kidney tissue in cadmium poisoning are statistically significant compared to control (p < 0.001). Glutathione and LA applied along with cadmium lowered TBARS concentration and reduced XO activity (p < 0.001). Catalase activity in the kidney tissue was increased in the group, which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as physiological antioxidants applied with cadmium, have reduced the level of lipid peroxide and the activity of XO, and can be used as protectors in conditions of cadmium poisoning.

Protective effects of glutathione on teratogenicity of cadmium chloride in mice

Protective effects of glutathione on teratogenicity of cadmium chloride in mice

Protective effect of glutathione S-transferase-fused mutant staphylococcal enterotoxin C against Staphylococcus aureus-induced bovine mastitis

Recent studies have demonstrated that immunization with nontoxic mutant staphylococcal enterotoxin C (mSEC) provides protection against Staphylococcus aureus infection in mouse models. In the present study, we investigated whether vaccination with a glutathione S-transferase-fused SEC (GST-mSEC) can protect against S. aureus-induced bovine mastitis. Cows were immunized with the GST-mSEC plus alum adjuvant and then challenged with viable S. aureus by an intramammary route. The results showed that immunization with GST-mSEC-induced production of SEC-specific antibodies in sera and the high titers of antibodies could persist for over 12 weeks. Importantly, immunization with GST-mSEC also induced production of SEC-specific antibodies in milk. The somatic cell counts in the milk from S. aureus challenged quarters of vaccinated lactating cows were significantly lower than those of the non-vaccinated control animals. Furthermore, the sera from GST-mSEC-immunized cows significantly inhibited interferon-γ and tumor necrosis factor-α production from mouse spleen cells induced by wild-type SEC. These results suggest that vaccination with GST-mSEC provides protection against S. aureus-induced bovine mastitis and that the protection might be mediated by SEC-neutralizing antibodies.

Reactive oxygen species and the protective effects of glutathione and N‐acetyl cysteine on mercuric chloride toxicity in Neuro‐2A Cells.

The present study was designed to investigate reactive oxygen species (ROS), which are generated by mercuric chloride (HgCl2) in Neuro 2A cells, and to determine the protective effects of various antioxidants on Neuro‐2A cells. HgCl2 was shown to produce 1.9&amp;#61549;M and 9.2&amp;#61549;M hydrogen peroxide (H2O2) at 5mM and 10mM HgCl2, respectively. N‐acetyl‐cysteine (NAC) and reduced glutathione (GSH) were shown to reduce H2O2 and provide strong antioxidant properties, which may account for their added protective effect in HgCl2 toxicity. Superoxide increased at low concentrations of HgCl2 (1&amp;#61549;M to 5&amp;#61549;M) up to 388% to 450% compared control. Pretreatment with NAC, protected the Neuro‐2A in a dose dependent manner to 74% versus the LD10 value for HgCl2 at 5&amp;#61549;M, while GSH and CYS provided 95% and 48% protection, respectively, against HgCl2 LD10. Superoxide dismutase (SOD) did not significantly provide protective effects against HgCl2; however it reduces superoxide production slightly, suggesting that H2O2 was partially produced intracellularly. These results demonstrate that H2O2 and superoxide are generated in response to low levels of HgCl2. The antioxidant properties of GSH and NAC which are utilized in GSH synthesis and reduce H2O2 production effectively protect the Neuro‐2A cell from the toxicity of HgCl2. (Supported by a NIH grant NCRR: RR 03020)

In vitro protective effect of glutathione on xanthine oxidase-induced oxidative injury in rat intestinal epithelial cells

In vitro protective effect of glutathione on xanthine oxidase-induced oxidative injury in rat intestinal epithelial cells

Protective Effect of Glutathione Against Liver Warm Ischemia‐Reperfusion Injury in Rats is Associated with Regulation of P‐Selectin and Neutrophil Infiltration

We examined the effects of glutathione (GSH) preconditioning through the portal vein on rat warm liver ischemia reperfusion injury (I/R injury) and investigated the mechanisms involved. In rats with warm liver I/R injury, administration of GSH by means of the portal vein before ischemia increased the 7-day survival rates of rats after liver I/R from 38% to 75%. This effect was correlated with significantly improved liver function, depressed MDA content in the liver and fewer histologic features of hepatocyte injury. Intrahepatic expression of P-selectin and infiltration of neutrophils were increased significantly after liver I/R. GSH pretreatment decreased intrahepatic MPO content and the expression of P-selectin. However, it did not significantly affect the mRNA levels for P-selectin after liver I/R. Thus, preconditioning with GSH protects the liver against I/R injury by a mechanism dependent on free radical species scavenging, down-regulation of adhesion molecule expression and inhibition of neutrophil accumulation. These findings document the potential clinical utility of GSH to improve the overall success of diverse procedures, such as liver surgery and liver transplantation.

Protective effects of glutathione and cysteine on the methylmercury-induced striatal dopamine release in vivo

The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 μM increased extracellular DA levels to 1941 ± 199% in terms of basal levels. Infusion of MeHg 400 μM in GSH 400 μM pretreated animals, only increased striatal DA levels to 465 ± 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 μM after infusion of GSH 400 μM increased DA levels to 1019 ± 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 μM in CYS 400 μM -pretreated animals, increased striatal DA levels to 740 ± 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 μM in MET 400 μM pretreated animals increased striatal DA levels to 2011 ± 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 μM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with –SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.

139 Protective effects of glutathione on 5-florouracil induced myelosuppression in mice

139 Protective effects of glutathione on 5-florouracil induced myelosuppression in mice

Protective effects of glutathione on 5-fluorouracil-induced myelosuppression in mice.

The protective effects of glutathione (GSH) administration on myelosuppression induced by 5-fluorouracil (5-FU) were investigated in female BALB/c mice. Animals were allocated to four groups (16 mice/group). GSH was given orally at a dose of 800 mg/kg to groups 3 and 4 for 21 consecutive days (day 0 to day 20). 5-FU was repeatedly administered at a dose of 40 mg/kg to groups 2 and 3 for 1 week (day 7 to day 13) by gavage. Group 3 served as a combined treatment group and group 1 as a non-treated control group. The total observation period was 3 weeks. Body weight was measured once a week. A decrease in body weight due to 5-FU treatment was observed in groups 2 and 3 on day 14. Although the body weight in group 2 had not increased by 1-week after cessation of 5-FU treatment, the value in group 3 markedly recovered. Hematology, total nucleated myelocyte count and histopathology of bone marrow were carried out on day 14 and day 21. In groups 2 and 3, these examinations showed thrombocytopenia, leukopenia, reticulocytopenia and myelosuppression on day 14. However, platelets and bone marrow were less affected in group 3 than in group 2. On day 21, the thrombocytopenia in groups 2 and 3 was resolved. The myelosuppression, leukopenia and reticulocytopenia resolved in group 3, but not in group 2. Although simple microcytic anemia occurred delayed on day 21, it was less severe in group 3 than in group 2. Therefore, GSH may have preventive effects against 5-FU-induced hematopoietic toxicity, and accelerate recovery after cessation of 5-FU treatment.

The Mycotoxin Patulin Alters the Barrier Function of the Intestinal Epithelium: Mechanism of Action of the Toxin and Protective Effects of Glutathione

Patulin is a mycotoxin mainly found in apple and apple products. In addition to being toxic for animals, mutagenic, carcinogenic and teratogenic, patulin induces intestinal injuries, including epithelial cell degeneration, inflammation, ulceration, and hemorrhages. In a study of the cellular mechanisms associated with the intestinal toxicity of patulin, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14) were exposed to the mycotoxin. Micromolar concentrations of patulin were found to induce a rapid and dramatic decrease of transepithelial resistance (TER) in both cell lines without major signs of toxicity as assessed by the LDH release assay. Since TER reflects the organization of tight junctions, these data indicate that patulin affected the barrier function of the intestinal epithelium. The inhibitory effect of patulin on TER was closely associated with its reactivity for SH groups: (i) cysteine and glutathione prevented the cells from patulin injury; (ii) patulin toxicity was potentiated by buthionine sulfoximine, a specific glutathione-depleting agent; (iii) treatment of the cells with N-ethylmaleimide, a compound known to react with SH groups, resulted in a marked decrease of TER. Moreover, the inhibitory effect of patulin on TER was mimicked and potentiated by phenylarsine oxide, a specific inhibitor of protein tyrosine phosphatase (PTP). This cellular enzyme is a key regulator of intestinal epithelial barrier function. The active site of PTP contains a cysteine residue (Cys215) that is essential for phosphatase activity. Sulfhydryl-reacting compounds such as acetaldehyde decrease TER through covalent modification of Cys215 of PTP. We propose that the toxicity of patulin for intestinal cells involves, among other potential mechanisms, an inactivation of the active site of PTP.

Human sperm immobilizing activity of aminophenyl arsenic acid and its N-substituted quinazoline, pyrimidine, and purine derivatives: protective effect of glutathione

We examined the potential toxicity of pentavalent organic arsenicals for human sperm. We used computer-assisted sperm analysis to examine the effects of three aminophenyl arsenicals and their nine N-substituted quinazoline, pyrimidine, and purine derivatives on human sperm motility and kinematics in human semen and medium. Among the arsenicals examined, (aminophenylazo)-phenyl arsonic acid and its N-substituted pyrimidine derivative PHI-370 (2-methylthio-4-[(4′-aminophenylazo)-phenylarsonic acid] pyrimidine) exhibited rapid sperm immobilizing activity in medium with EC 50 values of 77 and 82 μM, respectively, and t 1/2 of < 3 min. Molecular modeling analysis indicated that sperm-immobilizing organic arsenicals exhibit high dipole moments (>7 Debyes). Sperm immobilizing activity of these arsenicals was completely abrogated in the presence of seminal plasma. Furthermore, coincubation of motile sperm with PHI-370 in the presence of reduced glutathione (GSH) resulted in dose-dependent protection of sperm motility and sperm motion parameters. Coincubation of the arsenical with GSH at a molar ratio of 1:20 resulted in 95% retention of sperm progressive motility. The mean values of the other sperm movement characteristics also showed > 90% protection. These observations suggest that the rapid sperm immobilizing activity of these pentavalent arsenicals may be as a result of direct binding of the arsenical with the sperm thiol components essential for sperm motility as well as induction of oxidative damage by disruption of sperm cell’s antioxidant system. Sodium arsanilate and its N-substituted pyrimidine derivative, PHI-370, are useful probes to further evaluate the mechanism of pentavalent arsanilate-induced human sperm dysfunction.

Quinolinic acid induces oxidative stress in rat brain synaptosomes.

The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

Protective effect of glutathione on the cytotoxicity caused by a combination of aluminum and iron in suspension‐cultured tobacco cells

The role of endogenous glutathione (GSH) in the protection of suspension‐cultured tobacco cells from aluminum (Al) toxicity was examined. Cells at the logarithmic phase of growth were treated with or without Al in nutrient medium prepared without Pi and EDTA. In the absence of Al, total GSH content (including oxidized glutathione [GSSG]) increased gradually. In the presence of Al, the increase of GSH was repressed. This effect was observed before the loss of plasma membrane integrity and the loss of cell viability. In contrast, GSSG content in cells increased in the presence of Al. GSH‐deprived cells were prepared by culturing cells with buthionine sulfoximine (an inhibitor of Γ‐glutamylcysteine synthetase) for 24 h. Total GSH content in GSH‐deprived cells was 6% of that in normal cells. The GSH‐deprived cells exhibited a higher degree of lipid peroxidation, increased accumulation of Al, and greater loss of viability than normal cells. These results suggest that GSH protects cells from the oxidative membrane damage caused by a combination of Al and Fe(II) possibly by both direct consumption of GSH and oxidation of GSH.

P2A15 - Protective effects of glutathione on teratogenicity of cadmium hydrochloride in mice

The toxicity of dialuric acid to pancreatic β cells, and the haemolytic action of divicine and isouramil involve auto-oxidation and redox cycling reactions. Divicine and isouramil are produced on hydrolysis of the fava bean glycosides, vicine and convicine. The mechanism of auto-oxidation of the three compounds as well as the acid hydrolysis product of vicine (provisionally assigned the structure 2-amino-4,5,6-trihydroxypyrimidine) has been studied. All four pyrimidines auto-oxidized rapidly at neutral pH, generating H2O2 by an O2−-dependent chain mechanism. Superoxide dismutase inhibited the initial oxidation, but inhibition was transitory, and after a lag period rapid oxidation occurred. The lag period varied with pH, temperature and pyrimidine concentration, and was much shorter for isouramil and divicine than for dialuric acid and acid-hydrolysed vicine. The initial rate of dialuric acid oxidation was greater and the acceleration less pronounced than with the other pyrimidines. A mechanism common to all four pyrimidines has been shown by kinetic analysis to account for nearly all the observations in the presence and absence of superoxide dismutase. Autocatalysis in the latter case is attributed mainly to the reactions reduced pyrimidine + oxidized pyrimidine ai 2 pyrimidine radical pyrimidine radical + O2 → oxidized pyrimidine + O2−Rate constants for these and other reactions are reported. At pH7.4 and 37° the lag period before 100 μM acid-hydrolysed vicine underwent rapid oxidation was approx. 15 min. Isouramil and divicine at an equivalent concentration gave lags of < 1 min, which became less at higher concentrations. Thus intracellular superoxide dismutase should provide only transitory protection against the oxidation products of dialuric acid, divicine or isouramil. Prolonged protection should only be achieved if accumulation of oxidized pyrimidine is also prevented.

4-hydroxynonenal, a lipid peroxidation product, inhibits glutathione peroxidase: Protective effect of glutathione

4-hydroxynonenal, a lipid peroxidation product, inhibits glutathione peroxidase: Protective effect of glutathione