Increase In GSSG Concentrations Research Articles

Investigating the Impact of Carbon Nanotube Nanoparticle Exposure on Testicular Oxidative Stress and Histopathological Changes in Swiss albino Mice.

Carbon nanotubes (CNTs) possess remarkable properties that make them valuable for various industrial applications. However, concerns have arisen regarding their potential adverse health effects, particularly in occupational settings. The main aim of this research was to examine the effects of short-term exposure to multiwalled carbon nanotube nanoparticles (MWCNT-NPs) on testicular oxidative stress in Swiss albino mice, taking into account various factors such as dosage, duration of exposure, and particle size of MWCNT-NP. In this study, 20 mice were used and placed into six different groups randomly. Four of these groups comprised four repetitions each, while the two groups served as the vehicle control with two repetitions each. The experimental groups received MWCNT-NP treatment, whereas the control group remained untreated. The mice in the experimental groups were exposed to MWCNT-NP for either 7 days or 14 days. Through oral administration, the MWCNT-NP solution was introduced at two distinct dosages: 0.45 and 0.90 μg, whereas the control group was subjected to distilled water rather than the MWCNT-NP solution. The investigation evaluated primary oxidative balance indicators-glutathione (GSH) and glutathione disulfide (GSSG)-in response to MWCNT-NP exposure. Significantly, a noticeable reduction in GSH levels and a concurrent increase in GSSG concentrations were observed in comparison to the control group. To better understand and explore the assessment of the redox status, the Nernst equation was used to calculate the redox potential. Intriguingly, the calculated redox potential exhibited a negative value, signifying an imbalance in the oxidative state in the testes. These findings suggest that short-term exposure to MWCNT-NP can lead to the initiation of testicular oxidative stress and may disrupt the male reproductive system. This is evident from the alterations observed in the levels of GSH and GSSG, as well as the negative redox potential. The research offers significant insights into the reproductive effects of exposure to MWCNTs and emphasizes the necessity of assessing oxidative stress in nanomaterial toxicity studies.

Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress

While in vitro work has revealed that dehydration and hyperthermia can elicit increased cellular and oxidative stress, in vivo research linking dehydration, hyperthermia, and oxidative stress is limited. The purpose of this study was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male, trained cyclists (power output (W) at lactate threshold (LT): 199 ± 19 W) completed 90 min of cycling exercise at 95% LT followed by a 5-km time trial (TT) in 4 trials: (i) euhydration in a warm environment (EU-W, control), (ii) dehydration in a warm environment (DE-W), (iii) euhydration in a thermoneutral environment (EU-T), and (iv) dehydration in a thermoneutral environment (DE-T) (W: 33.9 ± 0.9 °C; T: 23.0 ± 1.0 °C). Oxidized glutathione (GSSG) increased significantly postexercise in dehydration trials only (DE-W: p < 0.01, DE-T: p = 0.03), and while not significant, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) tended to increase postexercise in dehydration trials (p = 0.08 for both). Monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, we found evidence of increased cellular stress (measured via HSP) during all trials independent of hydration status and environment. Finally, both 90-min and 5-km TT performances were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia, and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat.

Doxorubicin and menadione decrease cell proliferation of Saccharomyces cerevisiae by different mechanisms

The aim of this study was to determine the impacts of doxorubicin and menadion on cell proliferation, cell distribution in accordance with the phases of the cell-cycle phase, glutathione concentration, ribonucleotide reductase expression, and Yap1 dependent redox-sensitive pathway activity using Saccharomyces cerevisiae as eukaryote cell model. Our data show that menadione induced cell cycle arrest in G1-phase, reduction of intracellular GSH, an increase in GSSG concentration, and dose-dependent increases in ribonucleotide reductase expression and the activity of Yap1 pathway. Doxorubicin induced cell cycle arrest in G1- and S-phases, increased GSH and GSSG concentrations, increased expression of ribonucleotide reductase, and modulated Yap-dependent pathway activity.

Sequential Opening of Mitochondrial Ion Channels as a Function of Glutathione Redox Thiol Status

Mitochondrial membrane potential (DeltaPsi(m)) depolarization contributes to cell death and electrical and contractile dysfunction in the post-ischemic heart. An imbalance between mitochondrial reactive oxygen species production and scavenging was previously implicated in the activation of an inner membrane anion channel (IMAC), distinct from the permeability transition pore (PTP), as the first response to metabolic stress in cardiomyocytes. The glutathione redox couple, GSH/GSSG, oscillated in parallel with DeltaPsi(m) and the NADH/NAD(+) redox state. Here we show that depletion of reduced glutathione is an alternative trigger of synchronized mitochondrial oscillation in cardiomyocytes and that intermediate GSH/GSSG ratios cause reversible DeltaPsi(m) depolarization, although irreversible PTP activation is induced by extensive thiol oxidation. Mitochondrial dysfunction in response to diamide occurred in stages, progressing from oscillations in DeltaPsi(m) to sustained depolarization, in association with depletion of GSH. Mitochondrial oscillations were abrogated by 4'-chlorodiazepam, an IMAC inhibitor, whereas cyclosporin A was ineffective. In saponin-permeabilized cardiomyocytes, the thiol redox status was systematically clamped at GSH/GSSG ratios ranging from 300:1 to 20:1. At ratios of 150:1-100:1, DeltaPsi(m) depolarized reversibly, and a matrix-localized fluorescent marker was retained; however, decreasing the GSH/GSSG to 50:1 irreversibly depolarized DeltaPsi(m) and induced maximal rates of reactive oxygen species production, NAD(P)H oxidation, and loss of matrix constituents. Mitochondrial GSH sensitivity was altered by inhibiting either GSH uptake, the NADPH-dependent glutathione reductase, or the NADH/NADPH transhydrogenase, indicating that matrix GSH regeneration or replenishment was crucial. The results indicate that GSH/GSSG redox status governs the sequential opening of mitochondrial ion channels (IMAC before PTP) triggered by thiol oxidation in cardiomyocytes.

11] Redox potential of GSH/GSSG couple: Assay and biological significance

Publisher Summary Redox-signaling mechanisms function in cell regulation and growth control. Agents altering glutathione (GSH) concentration affect the transcription of detoxification enzymes, cell proliferation, and apoptosis. GSH, GSH S-conjugates, and its disulfide form (GSSG), or the redox state of the GSH/GSSG couple provide a mechanistic control or signal for functional changes. A loss or oxidation of GSH occurs in association with differentiation both in vitro and in vivo and during apoptosis. In contrast, increases in GSH and/or a reduction of the GSH/GSSG pool is associated with growth stimulation by nutrients and growth factors. Thus, the balance of GSH and GSSG may not only reflect oxidative stress but may reflect changes in redox signaling and control. The most widely used indicator of the redox state of the GSH pool is the ratio of GSH to GSSG. The cellular balance of GSH and GSSG provides a dynamic indicator of oxidative stress. Although GSH is synthesized continuously and has various fates in cells, these rates are generally slow relative to the turnover by the oxidation-reduction cycle. The activity of the GSSG reductase is dependent on GSSG concentration. During acute oxidative stress, GSH concentration decreases and the associated increase in GSSG concentration results in an increased turnover of the GSH/GSSG cycle.

GLUTATHIONE STATUS IN TRAINED AND UNTRAINED HUMANS

Glutathione is a tripeptide that has antioxidant properties and is involved in the regulation of redox sensitive signal transduction. Physical exercise may increase glutathione oxidation in vivo. The ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) has been used as an indicator for assessing exercise-induced oxidative stress. This study examined the effect a Bruce GTX protocol on the GSH:GSSG ratio in trained (n = 14; VO2peak = 55.7 ± 8.0 ml/kg/min) and untrained (n = 10; VO2peak = 38.6 ± 5.4 ml/kg/min) individuals. Blood samples were collected prior to, immediately post, and 1 hr post exercise. A 2 × 3 repeated measures ANOVA revealed that the pre exercise ratio of GSH:GSSG did not differ between trained and untrained subjects. The GSH:GSSG ratio in trained subjects remained stable after exercise, yet was significantly lower in untrained subjects immediately post exercise (p < 0.05), due to an increase in GSSG concentrations. Values measured 1 hr post exercise, in untrained subjects, returned to pre exercise values (p>0.05), indicating rapid recovery of GSH. These results demonstrate a difference between trained and untrained subjects in response to a GXT protocol and may support the notion that training modifies cellular antioxidant properties. Further studies should focus on the role of the GSH:GSSG ratio in signal transduction and adaptation to training.Table

Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin

Oxidative damage to the liver of lipopolysaccharide-treated rats was evaluated using four parameters: level of lipid peroxidation, changes in total GSH and GSSG concentrations and hepatic morphology. Bacterial lipopolysaccharide (10 mg/kg b.w.) was injected i.p. either at 6, 16 or 24 h before animals were killed. Lipopolysaccharide increased lipid peroxidation most dramatically when it was injected 6 h before killing. Hepatic total GSH increased after lipopolysaccharide in a time-dependent manner. The highest level of GSSG and largest GSSG/total GSH ratio were also observed in the group of animals injected with lipopolysaccharide 6 h before tissue collection. In a second study, lipopolysaccharide was injected 6 h before the animals were killed, with or without 1 mg/kg b.w. melatonin. Melatonin totally abolished lipopolysaccharide-induced increased in lipid peroxidation, exaggerated the rise in total GSH and reversed the increase in GSSG concentration. The liver showed obvious histological degenerative changes after lipopolysaccharide, effects that were counteracted by melatonin administration. The protection conferred by melatonin is presumably due to its antioxidant activity.

Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin

Oxidative damage to the liver of lipopolysaccharide-treated rats was evaluated using four parameters: level of lipid peroxidation, changes in total GSH and GSSG concentrations and hepatic morphology. Bacterial lipopolysaccharide (10 mg/kg b.w.) was injected i.p. either at 6, 16 or 24 h before animals were killed. Lipopolysaccharide increased lipid peroxidation most dramatically when it was injected 6 h before killing. Hepatic total GSH increased after lipopolysaccharide in a time-dependent manner. The highest level of GSSG and largest GSSG/total GSH ratio were also observed in the group of animals injected with lipopolysaccharide 6 h before tissue collection. In a second study, lipopolysaccharide was injected 6 h before the animals were killed, with or without 1 mg/kg b.w. melatonin. Melatonin totally abolished lipopolysaccharide-induced increased in lipid peroxidation, exaggerated the rise in total GSH and reversed the increase in GSSG concentration. The liver showed obvious histological degenerative changes after lipopolysaccharide, effects that were counteracted by melatonin administration. The protection conferred by melatonin is presumably due to its antioxidant activity.

The influence of systemic hypoxia and reoxygenation on the glutathione redox system of brain, liver, lung and plasma in newborn rats.

The concentrations of reduced (GSH) and oxidized glutathione (glutathione disulfide, GSSG) in lung, liver, brain and plasma of newborn rats were investigated under the condition of reversible hypoxia. Brain and lung of newborn rats seem to be susceptible to reversible hypoxia. We found an increase in GSSG concentration after hypoxia in these organs. This alteration of the GSH-GSSG redox system was reversible within 2 hours of reoxygenation. A second increase in cerebral GSSG concentration after 4 hours of reoxygenation was connected with fasting during the experiment. In the liver we found a hypoxia dependent decrease in the GSH level, followed by a decrease in GSSG concentration. The increased GSSG concentrations in lung and brain are accompanied by an enhancement of plasma GSSG concentration.

Nitrofurantoin-induced pulmonary toxicity: In vivo evidence for oxidative stress-mediated mechanisms

The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin-treated rats. In addition, nitrofurantoin did not alter the pulmonary Superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage.

Influence of complete and pronounced incomplete cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in the rat.

Abstract: The influence of complete and pronounced incomplete cerebral ischemia on cortical concentrations of reduced (GSH) and oxidized (GSSG) glutathione was studied in lightly anaesthetized (70% N2 O) rats. GSH was extracted with HCl‐methanol‐perchloric acid and GSSG with trichloroacetic acid in the presence of N‐ethylmaleimide and measured fluorometrically, giving normal concentrations in cortical tissue of about 2 and 0.01 μmol.g−1 respectively. Reversible complete ischemia was induced by increasing the intracranial pressure to above the systolic blood pressure by infusing mock CSF into the cisterna magna. Reversible pronounced incomplete ischemia was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. Whether complete or incomplete, a 30‐min ischemic period caused a similar decrease in cortical GSH concentration (to about 90% of control) without any concomitant accumulation of GSSG in the tissue (or in CSF). Prolongation of the ischemic period (complete ischemia) to maximally 120 min caused an almost linear decrease of the tissue glutathione concentration to 45% of the preischemic value. During subsequent recirculation following a 30 min period of either complete or pronounced incomplete ischemia, there was a further decrease in cortical GSH concentrations without a reciprocal increase in GSSG concentrations. Lipid peroxidation (verified by determination of malondialdehyde production) induced in brain cortical tissue in vitro caused oxidation of tissue GSH with accumulation of GSSG. As the observed decrease in GSH during brain ischemia in vivo was not accompanied by any reciprocal increase in GSSG the results fail to support the hypothesis that peroxidative damage occurs during or following brain ischemia. The finding of an unchanged GSSG concentration does, however, not exclude the possibility of an increased turnover rate in the glutathione reductase reaction. It is concluded that the observed decrease in tissue GSH concentration mainly reflects a decrease in the glutathione pool size, due to an imbalance between breakdown and synthesis secondary to tissue energy failure.