Cellular Cysteine Network and Neurodegeneration

2020 ◽  
pp. 303-325
Author(s):  
Shubhangi H. Pawar ◽  
Vishal S. Gulecha ◽  
Manoj S. Mahajan ◽  
Aman B Upaganiawar ◽  
Chandrashekhar D. Upasani
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Free Radical Scavenger ◽  
Cellular Damage ◽  
Radical Scavenger ◽  
Post Translational Modifications ◽  
Cellular Defense ◽  
Brain Antioxidants ◽  
The Brain ◽  
Oxidative Species

Oxidative stress is strongly linked to neurodegeneration and oxidative species can modify many amino acids and proteins in the brain. Cysteine amino acid is most susceptible to oxidative post-translational modifications (PTMs). Reversible or irreversible cysteine PTMs can cause dyshomeostasis, which further continued to cellular damage. Many cysteine dependent proteins and many non-proteins using cysteine as their structural components are affected by oxidative stress. Several cysteine dependent enzymes are acting as antioxidants. Cysteine is a major contributor to glutathione (GSH) and superoxide dismutase (SOD) synthesis. Cysteine precursor N-acetylcysteine (NAC) supplementation is proven as a potent free radical scavenger and increase brain antioxidants and subsequently potentiates the natural antioxidant cellular defense mechanism. Thus, in this chapter, the authors explore the linkage of cellular cysteine networks and neurodegenerative disorders.

A new prospective on the role of melatonin in diabetes and its complications

2019 ◽  
Vol 40 (1) ◽  
Author(s):  
Jia Xin Mok ◽  
Jack Hau Ooi ◽  
Khuen Yen Ng ◽  
Rhun Yian Koh ◽  
Soi Moi Chye
Keyword(s):  
Oxidative Stress ◽  
Molecular Level ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
The Past ◽  
Melatonin Administration ◽  
Cellular Apoptosis ◽  
Oxidative Species

Abstract Melatonin is a hormone secreted by the pineal gland under the control of the circadian rhythm, and is released in the dark and suppressed during the day. In the past decades, melatonin has been considered to be used in the treatment for diabetes mellitus (DM). This is due to a functional inter-relationship between melatonin and insulin. Elevated oxidative stress is a feature found in DM associated with diabetic neuropathy (DN), retinopathy (DR), nephropathy and cardiovascular disease. Reactive oxygen species (ROS) and nitrogen oxidative species (NOS) are usually produced in massive amounts via glucose and lipid peroxidation, and this leads to diabetic complications. At the molecular level, ROS causes damage to the biomolecules and triggers apoptosis. Melatonin, as an antioxidant and a free radical scavenger, ameliorates oxidative stress caused by ROS and NOS. Besides that, melatonin administration is proven to bring other anti-DM effects such as reducing cellular apoptosis and promoting the production of antioxidants.

scholarly journals Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 943 ◽  
Author(s):  
Helene Ismail ◽  
Zaynab Shakkour ◽  
Maha Tabet ◽  
Samar Abdelhady ◽  
Abir Kobaisi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Free Radical Scavenger ◽  
Health Concern ◽  
Radical Scavenger ◽  
History Of ◽  
Ionic Imbalance

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

scholarly journals Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Kazuyuki Miyamoto ◽  
Hirokazu Ohtaki ◽  
Kenji Dohi ◽  
Tomomi Tsumuraya ◽  
Dandan Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Death ◽  
Time Window ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Therapeutic Time Window

Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2∙-) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease inO2∙-levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.

scholarly journals Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Chakravarty ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipid ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Therapeutic Implications ◽  
Antioxidative Function ◽  
Reliable Marker

The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications.In vitrodose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

scholarly journals Melatonin protects the mouse testis against heat-induced damage

2020 ◽  
Vol 26 (2) ◽  
pp. 65-79 ◽  
Author(s):  
Pengfei Zhang ◽  
Yi Zheng ◽  
Yinghua Lv ◽  
Fuyuan Li ◽  
Lihong Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Male Fertility ◽  
Reactive Oxygen Species Generation ◽  
Free Radical Scavenger ◽  
Testicular Atrophy ◽  
Therapeutic Drug ◽  
Radical Scavenger ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Abstract Spermatogenesis, an intricate process occurring in the testis, is responsible for ongoing production of spermatozoa and thus the cornerstone of lifelong male fertility. In the testis, spermatogenesis occurs optimally at a temperature 2–4°C lower than that of the core body. Increased scrotal temperature generates testicular heat stress and later causes testicular atrophy and spermatogenic arrest, resulting in a lower sperm yield and therefore impaired male fertility. Melatonin (N-acetyl-5-methoxytryptamine), a small neuro-hormone synthesized and secreted by the pineal gland and the testis, is widely known as a potent free-radical scavenger; it has been reported that melatonin protects the testis against inflammation and reactive oxygen species generation thereby playing anti-inflammatory, -oxidative and -apoptotic roles in the testis. Nevertheless, the role of melatonin in the testicular response to heat stress has not been studied. Here, by employing a mouse model of testicular hyperthermia, we systematically investigated the testicular response to heat stress as well as the occurrence of autophagy, apoptosis and oxidative stress in the testis. Importantly, we found that pre-treatment with melatonin attenuated heat-induced apoptosis and oxidative stress in the testis. Also, post-treatment with melatonin promoted recovery of the testes from heat-induced damage, probably by maintaining the integrity of the Sertoli cell tight-junction. Thus, we for the first time provide the proof of concept that melatonin can protect the testis against heat-induced damage, supporting the potential future use of melatonin as a therapeutic drug in men for sub/infertility incurred by various testicular hyperthermia factors.

scholarly journals Use of Melatonin in Oxidative Stress Related Neonatal Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 477
Author(s):  
Gabriella D’Angelo ◽  
Roberto Chimenz ◽  
Russel J. Reiter ◽  
Eloisa Gitto
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Perinatal Period ◽  
Oxygen Radical ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
Perinatal Brain Injury ◽  
Radical Generation ◽  
Prophylactic Use

Reactive oxygen species have a crucial role in the pathogenesis of perinatal diseases. Exposure to inflammation, infections, or high oxygen concentrations is frequent in preterm infants, who have high free iron levels that enhance toxic radical generation and diminish antioxidant defense. The peculiar susceptibility of newborns to oxidative stress supports the prophylactic use of melatonin in preventing or decreasing oxidative stress-mediated diseases. Melatonin, an effective direct free-radical scavenger, easily diffuses through biological membranes and exerts pleiotropic activity everywhere. Multiple investigations have assessed the effectiveness of melatonin to reduce the “oxygen radical diseases of newborn” including perinatal brain injury, sepsis, chronic lung disease (CLD), and necrotizing enterocolitis (NEC). Further studies are still awaited to test melatonin activity during perinatal period.

Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Gi Tract ◽  
Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

scholarly journals Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tomomi Masuda ◽  
Masamitsu Shimazawa ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Apoptotic Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Free Radical Scavenger ◽  
Age Related Macular Degeneration ◽  
Radical Scavenger ◽  
Retinal Diseases ◽  
Age Related

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

scholarly journals Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

2010 ◽  
Vol 30 (9) ◽  
pp. 1625-1636 ◽  
Author(s):  
Jeffrey J Lochhead ◽  
Gwen McCaffrey ◽  
Colleen E Quigley ◽  
Jessica Finch ◽  
Kristin M DeMarco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Critical Role ◽  
Brain Barrier ◽  
Central Component ◽  
Radical Scavenger ◽  
Cerebral Microvessels ◽  
Disease States ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity.

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