Oxidative Stress and Neurological Diseases: Is Glutathione Depletion a Common Factor?

2018 ◽  
pp. 355-384
Author(s):  
Jaswinder S. Bains ◽  
Christopher A. Shaw
Keyword(s):  
Oxidative Stress ◽  
Neurological Diseases ◽  
Common Factor ◽  
Glutathione Depletion

scholarly journals ATF4 is an oxidative stress–inducible, prodeath transcription factor in neurons in vitro and in vivo

2008 ◽  
Vol 205 (5) ◽  
pp. 1227-1242 ◽  
Author(s):  
Philipp S. Lange ◽  
Juan C. Chavez ◽  
John T. Pinto ◽  
Giovanni Coppola ◽  
Chiao-Wang Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Neurological Diseases ◽  
Glutathione Depletion ◽  
Bzip Transcription Factor ◽  
Behavioral Recovery ◽  
Activating Transcription Factor 4 ◽  
Death And Loss

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress–inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress–induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative death by ATF4 deletion was associated with decreased consumption of the antioxidant glutathione. Forced expression of ATF4 was sufficient to promote cell death and loss of glutathione. In ATF4−/− neurons, restoration of ATF4 protein expression reinstated sensitivity to oxidative death. In addition, ATF4−/− mice experienced significantly smaller infarcts and improved behavioral recovery as compared with wild-type mice subjected to the same reductions in blood flow in a rodent model of ischemic stroke. Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo.

Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?

2017 ◽  
Vol 18 (6) ◽  
pp. 705-718 ◽  
Author(s):  
Andreia Neves Carvalho ◽  
Omidreza Firuzi ◽  
Maria Joao Gama ◽  
Jack van Horssen ◽  
Luciano Saso
Keyword(s):  
Oxidative Stress ◽  
Neurological Diseases

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reduced Glutathione ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Glutathione Depletion ◽  
Swim Test ◽  
Stress Markers ◽  
Immobility Time ◽  
Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

A toxicogenomics approach for risk assessment of glutathione depletion and oxidative stress-induced nongenotoxic hepatocarcinogenesis in the rat liver

2006 ◽  
Vol 164 ◽  
pp. S5-S6
Author(s):  
Takeki Uehara ◽  
Naoki Kiyosawa ◽  
Atsushi Ono ◽  
Toshikazu Miyagishima ◽  
Tetsuro Urushidani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Assessment ◽  
Rat Liver ◽  
Glutathione Depletion ◽  
And Oxidative Stress

Pivotal role of glutathione depletion in plasma-induced endothelial oxidative stress during sepsis

2008 ◽  
Vol 36 (8) ◽  
pp. 2328-2334 ◽  
Author(s):  
Olivier Huet ◽  
Christaine Cherreau ◽  
Carole Nicco ◽  
Laurent Dupic ◽  
Marc Conti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pivotal Role ◽  
Glutathione Depletion

scholarly journals Detecting Validated Intracellular ROS Generation with 18F-dihydroethidine-Based PET

2021 ◽  
Author(s):  
Edward C. T. Waters ◽  
Friedrich Baark ◽  
Zilin Yu ◽  
Filipa Mota ◽  
Thomas R. Eykyn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Contractile Function ◽  
Ex Vivo ◽  
Glutathione Depletion ◽  
Ros Generation ◽  
Cardiac Contractile ◽  
Rat Hearts ◽  
Intracellular Ros ◽  
Cardiac Contractile Dysfunction

Abstract Purpose To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress. Procedures The sensitivity of [18F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [18F]DHE (50–150 kBq.min−1) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress. Results [18F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [18F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation. Conclusion [18F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.

scholarly journals Ochratoxin A-Induced Hepatotoxicity through Phase I and Phase II Reactions Regulated by AhR in Liver Cells

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 377 ◽  
Author(s):  
Hye Soo Shin ◽  
Hyun Jung Lee ◽  
Min Cheol Pyo ◽  
Dojin Ryu ◽  
Kwang-Won Lee
Keyword(s):  
Oxidative Stress ◽  
Phase I ◽  
Ochratoxin A ◽  
Phase Ii ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Aryl Hydrocarbon ◽  
Similar Mode ◽  
Phase I And Ii

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress.

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