Molecular mechanisms of melatonin’s protection against high-LET radiation: implications for space travel

2020 ◽  
Vol 3 (4) ◽  
pp. 503-514
Author(s):  
Mu-Tai Liu ◽  
Russel J Reiter
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Space Mission ◽  
Galactic Cosmic Rays ◽  
Melatonin Treatment ◽  
Solar Particle Events ◽  
Carbon Ion ◽  
Novel Technologies ◽  
Particle Irradiation

During a deep space mission, the central nervous system (CNS) and other organs are exposed to galactic cosmic rays and solar particle events. Health risks associated with various organs and systems are important issues in a long-term spaceflight. Potential CNS damage during a space mission could alter cognitive functions which might impact performance and individual’s health. The neuronal injury originating from exposure to 56Fe particle irradiation involves the elevated oxidative stress which can be inhibited by melatonin pretreatment. Melatonin exerts potent neuroprotective effects against carbon ion-induced mitochondrial dysfunction and apoptosis in the mouse brain. A significant increase in the count of immature neurons and proliferating cells was detected in the mice under 56Fe particle irradiation cotreated with the melatonin metabolite, AFMK. Melatonin treatment also significantly reduced the carbon ion-induced apoptotic cells and elevated oxidative stress in the mouse testis. The results suggest that melatonin treatment is a potential strategy to protect against space radiation hazards. Spaceflight-induced molecular, cellular, and physiologic changes lead to alterations across many organs and systems. Epigenetic, gene expression, inflammatory, and metabolic responses to spaceflight should be examined and means to safe-guard against these changes in upcoming missions. Precision medicine will be crucial for assessing and augmenting efficacy of melatonin or other medications in astronauts. In addition, enhancing radio-resistance of humans is a novel strategy for a long-term space mission. Further investigations with a combination of melatonin and other novel technologies are warranted to better alleviate HZE particle irradiation-induced damage to astronauts on long-term space exploration missions. 

scholarly journals Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Lara Macchioni ◽  
Davide Chiasserini ◽  
Letizia Mezzasoma ◽  
Magdalena Davidescu ◽  
Pier Luigi Orvietani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Rpe Cells ◽  
Age Related ◽  
Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

Total Body Irradiation Causes Residual Bone Marrow Injury by Induction of Persistent Oxidative Stress in Murine Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3209-3209
Author(s):  
Yong Wang ◽  
Lingbo Liu ◽  
Senthil Kumar Pazhanisamy ◽  
Aimin Meng ◽  
Daohong Zhou
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Total Body Irradiation ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Tissue Injury ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
Total Body

Abstract Abstract 3209 Poster Board III-146 Ionizing radiation (IR) and/or chemotherapy cause not only acute tissue injury but also have late effects including long-term bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to induction of hematopoietic stem cell (HSC) senescence. However, neither the molecular mechanisms by which IR and/or chemotherapy induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury, which were investigated in the present study using a total body irradiation (TBI) mouse model. The results showed that exposure of mice to 6.5 Gy TBI induced a persistent increase in reactive oxygen species (ROS) production in HSCs only for up to 8 weeks, primarily via up-regulation of NADPH oxidase 4 (NOX4). This finding provides the foremost direct evidence demonstrating that in vivo exposure to IR causes persistent oxidative stress selectively in a specific population of BM hematopoietic cells (HSCs). The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double strand breaks, inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetyl-cysteine (NAC) after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. These findings suggest that selective induction of chronic oxidative stress in HSCs by TBI leads to induction of HSC senescence and residual BM injury and that antioxidant therapy may be used as an effective strategy to mitigate IR- and chemotherapy-induced residual BM injury. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nutrients and Oxidative Stress: Friend or Foe?

2018 ◽  
Vol 2018 ◽  
pp. 1-24 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan ◽  
Winnie-Pui-Pui Liew
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Noncommunicable Diseases ◽  
Intrinsic Factors ◽  
Fat Consumption ◽  
Dietary Choices ◽  
Protein Diets ◽  
Cell Signaling Pathways

There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

scholarly journals Utilisation of Moon Regolith for Radiation Protection and Thermal Insulation in Permanent Lunar Habitats

2021 ◽  
Vol 11 (9) ◽  
pp. 3853
Author(s):  
Yulia Akisheva ◽  
Yves Gourinat
Keyword(s):  
Radiation Protection ◽  
Thermal Insulation ◽  
Thermal Protection ◽  
Galactic Cosmic Rays ◽  
Radiation Shielding ◽  
Dose Equivalent ◽  
Specific Data ◽  
Solar Particle Events ◽  
Lunar Rovers

In the context of a sustainable long-term human presence on the Moon, solutions for habitat radiation and thermal protection with regolith are investigated. Regolith compression is studied to choose the optimal density-thickness combination in terms of radiation shielding and thermal insulation. The applied strategy is to protect the whole habitat from the hazards of galactic cosmic rays and design a dedicated shelter area for protection during solar particle events, which eventually may be a lava tube. Simulations using NASA’s OLTARIS tool show that the effective dose equivalent decreases significantly when a multilayer structure mainly constituted of regolith and other available materials is used instead of pure regolith. The computerised anatomical female model is considered here because future missions will be mixed crews, and, generally, more sex-specific data are required in the field of radiation protection and human spaceflight. This study shows that if reasonably achievable radioprotection conditions are met, mixed crews can stay safely on the lunar surface. Compressed regolith demonstrates a significant efficiency in thermal insulation, requiring little energy management to keep a comfortable temperature inside the habitat. For a more complete picture of the outpost, the radiation protection of lunar rovers and extravehicular mobility units is considered.

scholarly journals SIRT1-Related Signaling Pathways and Their Association With Bronchopulmonary Dysplasia

2021 ◽  
Vol 8 ◽  
Author(s):  
Kun Yang ◽  
Wenbin Dong
Keyword(s):  
Oxidative Stress ◽  
Mental Health ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Bronchopulmonary Dysplasia ◽  
Premature Infants ◽  
Molecular Mechanisms ◽  
Physical And Mental Health ◽  
Short And Long Term

Bronchopulmonary dysplasia (BPD) is a chronic and debilitating disease that can exert serious and overwhelming effects on the physical and mental health of premature infants, predominantly due to intractable short- and long-term complications. Oxidative stress is one of the most predominant causes of BPD. Hyperoxia activates a cascade of hazardous events, including mitochondrial dysfunction, uncontrolled inflammation, reduced autophagy, increased apoptosis, and the induction of fibrosis. These events may involve, to varying degrees, alterations in SIRT1 and its associated targets. In the present review, we describe SIRT1-related signaling pathways and their association with BPD. Our intention is to provide new insights into the molecular mechanisms that regulate BPD and identify potential therapeutic targets for this debilitating condition.

Therapeutic Potential of Caffeic Acid Phenethyl Ester (CAPE) in Diabetes

2019 ◽  
Vol 25 (37) ◽  
pp. 4827-4836 ◽  
Author(s):  
Valeria Pittalà ◽  
Loredana Salerno ◽  
Giuseppe Romeo ◽  
Rosaria Acquaviva ◽  
Claudia Di Giacomo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caffeic Acid ◽  
Antioxidant Defense ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Caffeic Acid Phenethyl Ester ◽  
Sugar Levels ◽  
Main Components

Diabetes mellitus is a complex metabolic disease characterized by high blood sugar levels. Different pathogenic processes are involved in the etiology of the disease. Indeed, chronic diabetes hyperglycemia is often associated with severe long-term complications including cardiovascular symptoms, retinopathy, nephropathy, and neuropathy. Although the precise molecular mechanisms underlying diabetes are not yet clear, it is widely accepted that increased levels of oxidative stress are involved in the onset, development and progression of diabetes and its related complications. In this regard, the use of natural antioxidant polyphenols, able to control free radical production, to increase intracellular antioxidant defense and to prevent the onset of oxidative stress, can be of high interest. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic substance, is one of the main components of propolis. Due to its multifaceted biological activities, including antioxidant, antimicrobial, anti-inflammatory, antitumor, and immunomodulatory effects, CAPE has received great attention during the last few decades. In the present paper the therapeutic potential of CAPE in diabetes is extensively reviewed.

Melatonin Administration from 2000 to 2020 to Human Newborns with Hypoxic-Ischemic Encephalopathy

2020 ◽  
Author(s):  
Gabriella D'angelo ◽  
Laura Cannavò ◽  
Russel J. Reiter ◽  
Eloisa Gitto
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Perinatal Asphyxia ◽  
Hypoxic Ischemic Encephalopathy ◽  
Melatonin Treatment ◽  
The Past ◽  
Melatonin Administration ◽  
Key Points ◽  
Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is the main cause of long-term neurodevelopmental morbidity in term born infants worldwide. Melatonin is a hormone with antioxidant and anti-inflammatory effects that make it a promising molecule for the treatment of perinatal asphyxia. Probably, the synergistic use of hypothermia associated with melatonin treatment may improve the neurological outcome in infants with HIE. In the past 20 years, the efficacy of melatonin in reducing oxidative stress has been demonstrated in animals; however, clinical trials with sufficient sample size of newborns are lacking to date.Since in 2000 we were among the first to study the neuroprotective properties of melatonin on infants, in this review, we want to summarize the advantages and limitations of the investigations conducted to date. Key Points

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