Glutathione

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and N-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic SN2 substitution of 3-Cl by GSH; this pathway is NADPH indep...

The extracellular and intracellular metabolites formed upon exposure of activated sludge microorganisms to a sublethal concentration of N-ethylmaleimide were monitored by liquid chromatography with ion trap mass spectrometry. The metabolite N-ethylsuccinimido-S-glutathione (m/z 433) was converted rapidly to N-(2-oxoethyl)-2,2-(propionylamino)propanamide (m/z 187) and N-ethylmaleamic acid (m/z 144).

In Tetrahymena, glutathione is synthesized from the same precursors as it is in higher animals and is present in similar intracellular concentrations. The intracellular thiol-disulfide ratio is also identical to that of mammalian tissues, due to the activity of glutathione reductase. The intracellular GSH-level was found to be dependent on the sulfur-containing amino acids in the chemically defined medium.

Glutathione (GSH) and cysteine (CysH) have both been implicated in the biogenesis of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD). However, recent studies have shown that only CysH is transported across the membrane of isolated melanosomes, and that the positive regulation of CysH in pigment cells leads to an increased production of 5-S-CD. In the present study, the question was examined as to whether melanin precursors and tyrosinase could be coregulated by cellular thiols. To address this issue, the levels of CysH and GSH were varied in normal melanocytes and melanoma cells using buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis. Treatment with 50-100 microM BSO decreased GSH levels to less than 10% of control, and increased CysH levels between two- and five-fold in both cell types. Concomitant with this, an increase in the ratio of 5-S-CD to DOPA and a decrease in the pigment content of the cells were observed. The decrease in cell pigmentation was associated...

These experiments tested the hypothesis that short-term endurance exercise training would rapidly improve (within 5 days) the diaphragm oxidative/antioxidant capacity and protect the diaphragm against contraction-induced oxidative stress. To test this postulate, male Sprague-Dawley rats (6 weeks old) ran on a motorized treadmill for 5 consecutive days (40-60 min x day(-1)) at approximately 65% maximal oxygen uptake. Costal diaphragm strips were excised from both sedentary control (CON, n=14) and trained (TR, n=13) animals 24 h after the last exercise session, for measurement of in vitro contraction properties and selected biochemical parameters of oxidative/antioxidant capacity. Training did not alter diaphragm force-frequency characteristics over a full range of submaximal and maximal stimulation frequencies (P > 0.05). In contrast, training improved diaphragm resistance to fatigue as contraction forces were better-maintained by the diaphragms of the TR animals during a submaxim...

The aim of this study was to evaluate the negative effects of the Pringle maneuver on pancreatic tissue with respect to the time of performing the maneuver. Moreover, the efficacy of octreotide therapy on pancreatic changes at the time of the Pringle maneuver was assessed. Fifty male Wistar Albino rats were randomized into 5 groups. The groups were formed as follows: Group A: sham operation, Group B: Pringle maneuver for 30 min plus octreotide (PM30-OCT), Group C: Pringle maneuver for 60 min plus octreotide (PM60-OCT) and Group D: Pringle maneuver for 30 min plus 0.9 % saline solution (PM30-SS), Pringle maneuver for 60 min plus 0.9 % saline solution (PM60-SS, Group E). Blood samples for the evaluation of both amylase and lipase levels were taken via the portal vein. Levels of glutathione, glutathione reductase, catalase, myeloperoxidase, nitric oxide, xanthine oxidase, malondialdehyde, tumour necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were assessed in the ...

The antioxidant properties of the fruit of the Rosa roxburghii (RR) plant have been associated with several putative health promoting effects. The possible cytotoxic, mutagenic/antimutagenic and genotoxic effects of RR fruit extract were investigated. The effect on antioxidant status and protection against induced oxidative stress were also investigated using primary rat hepatocytes. A RR fruit extract containing 45 g/L total ascorbic acid and 65 g/L total polyphenols was used in this study. Dilutions up to 0.08% (v/v) increased significantly the antioxidant status in primary rat hepatocytes. The glutathione redox state was decreased with RR treatment but was increased in Chang liver cells and MT-2 lymphoblast. No cyto- or genotoxicity were observed at levels of up to 5% (v/v) of the fruit extract. In addition, a significant protection against t-BHP induced oxidative stress was observed in primary rat hepatocytes. The Ames test revealed no mutagenic activity using the Salmonella typhimurium strains TA98, TA100 and TA102. A significant antimutagenic effect of the extract was observed against the metabolic activated mutagens 2-acetylaminofluorene and aflatoxin B1 and to a lesser extent against methyl methanesulfonate. It is concluded that these results support the associated health promoting potential of Rosa Roxburghii fruit and in particular against oxidative stress. Copyright © 2007 John Wiley & Sons, Ltd.

It is generally agreed that physiological levels of melatonin, a hormone secreted by the pineal gland, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects that pinealectomy and the administration of exogenous melatonin have on the brains, testes, duodena and stomachs of rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, and catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD) and malondialdehyde (MDA) levels. The rats were divided into the following five groups (eight rats in each group): sham (non-Px), Px+ vehicle, Px+ melatonin (10 mg/kg given daily intraperitoneally for a week), melatonin and ethyl alcohol. The antioxidant levels in the tissue of Px rats were significantly lower than in those of the sham group. Administering melatonin significantly increased antioxidant levels (p < 0.05). The Px rats also showed a significant increase in MDA levels when com...

1Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free β-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction.2Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days.3Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy.4Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes.5These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect.Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free β-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction.Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days.Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy.Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes.These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect.

Abstract:  The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.

Intracellular antioxidants include low molecular weight scavengers of oxidizing species, and enzymes which degrade superoxide and hydroperoxides. Such antioxidants systems prevent the uncontrolled formation of free radicals and activated oxygen species, or inhibit their ...

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (l: 10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min−1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 μ M and decreased the conversion rate to 0.012 min−1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 m M and the conversion of the d,l-HM-PAO due to GSH alone should...

A comparative study concerning the inhibition of the enzymatic browning in Red delicious apple slices and pulp stored for 24h at 4, 25, and 35° C was carried out between the thiol containing compounds; cysteine, glutathione and Maillard reaction products (MRPs) ...