Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

The developing brain is extremely sensitive to many chemicals. Perinatal exposure to neurotoxicants has been implicated in several neurodevelopmental disorders, including autism spectrum disorder, attention-deficit hyperactive disorder, and schizophrenia. Studies of the molecular and cellular events related to developmental neurotoxicity have identified a number of “adverse outcome pathways,” many of which share oxidative stress as a key event. Oxidative stress occurs when the balance between the production of free oxygen radicals and the activity of the cellular antioxidant system is dysregulated. In this review, we describe some of the developmental neurotoxins that target the antioxidant system and the mechanisms by which they elicit stress, including oxidative phosphorylation in mitochondria and plasma membrane redox system in rodent models. We also discuss future directions for identifying adverse outcome pathways related to oxidative stress and developmental neurotoxicity, with the goal of improving our ability to quickly and accurately screen chemicals for their potential developmental neurotoxicity.

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Redox Regulation in Aging Lungs and Therapeutic Implications of Antioxidants in COPD

Antioxidants ◽

10.3390/antiox10091429 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1429

Author(s):

Hirofumi Kiyokawa ◽

Yuma Hoshino ◽

Kazuhiro Sakaguchi ◽

Shigeo Muro ◽

Junji Yodoi

Keyword(s):

Oxidative Stress ◽

Respiratory System ◽

Redox Regulation ◽

Wide Spectrum ◽

Redox System ◽

Cellular Aging ◽

Future Directions ◽

Therapeutic Implications ◽

Chronic Lung Diseases ◽

Cellular Apoptosis

Mammals, including humans, are aerobic organisms with a mature respiratory system to intake oxygen as a vital source of cellular energy. Despite the essentiality of reactive oxygen species (ROS) as byproducts of aerobic metabolism for cellular homeostasis, excessive ROS contribute to the development of a wide spectrum of pathological conditions, including chronic lung diseases such as COPD. In particular, epithelial cells in the respiratory system are directly exposed to and challenged by exogenous ROS, including ozone and cigarette smoke, which results in detrimental oxidative stress in the lungs. In addition, the dysfunction of redox regulation due to cellular aging accelerates COPD pathogenesis, such as inflammation, protease anti-protease imbalance and cellular apoptosis. Therefore, various drugs targeting oxidative stress-associated pathways, such as thioredoxin and N-acetylcysteine, have been developed for COPD treatment to precisely regulate the redox system. In this review, we present the current understanding of the roles of redox regulation in the respiratory system and COPD pathogenesis. We address the insufficiency of current COPD treatment as antioxidants and discuss future directions in COPD therapeutics targeting oxidative stress while avoiding side effects such as tumorigenesis.

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SDHI Fungicide Toxicity and Associated Adverse Outcome Pathways: What Can Zebrafish Tell Us?

International Journal of Molecular Sciences ◽

10.3390/ijms222212362 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12362

Author(s):

Constantin Yanicostas ◽

Nadia Soussi-Yanicostas

Keyword(s):

Oxidative Stress ◽

Adverse Effects ◽

Succinate Dehydrogenase ◽

Adverse Outcome ◽

Current Knowledge ◽

Developmental Toxicity ◽

Axon Growth ◽

Brachydanio Rerio ◽

Almost All ◽

Adverse Outcome Pathways

Succinate dehydrogenase inhibitor (SDHI) fungicides are increasingly used in agriculture to combat molds and fungi, two major threats to both food supply and public health. However, the essential requirement for the succinate dehydrogenase (SDH) complex—the molecular target of SDHIs—in energy metabolism for almost all extant eukaryotes and the lack of species specificity of these fungicides raise concerns about their toxicity toward off-target organisms and, more generally, toward the environment. Herein we review the current knowledge on the toxicity toward zebrafish (Brachydanio rerio) of nine commonly used SDHI fungicides: bixafen, boscalid, fluxapyroxad, flutolanil, isoflucypram, isopyrazam, penthiopyrad, sedaxane, and thifluzamide. The results indicate that these SDHIs cause multiple adverse effects in embryos, larvae/juveniles, and/or adults, sometimes at developmentally relevant concentrations. Adverse effects include developmental toxicity, cardiovascular abnormalities, liver and kidney damage, oxidative stress, energy deficits, changes in metabolism, microcephaly, axon growth defects, apoptosis, and transcriptome changes, suggesting that glycometabolism deficit, oxidative stress, and apoptosis are critical in the toxicity of most of these SDHIs. However, other adverse outcome pathways, possibly involving unsuspected molecular targets, are also suggested. Lastly, we note that because of their recent arrival on the market, the number of studies addressing the toxicity of these compounds is still scant, emphasizing the need to further investigate the toxicity of all SDHIs currently used and to identify their adverse effects and associated modes of action, both alone and in combination with other pesticides.

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Retinoids and developmental neurotoxicity: Utilizing toxicogenomics to enhance adverse outcome pathways and testing strategies

Reproductive Toxicology ◽

10.1016/j.reprotox.2020.06.007 ◽

2020 ◽

Vol 96 ◽

pp. 102-113

Author(s):

Hao Chen ◽

Megan A. Chidboy ◽

Joshua F. Robinson

Keyword(s):

Adverse Outcome ◽

Developmental Neurotoxicity ◽

Testing Strategies ◽

Adverse Outcome Pathways

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Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast

Archives of Toxicology ◽

10.1007/s00204-020-02752-z ◽

2020 ◽

Vol 94 (5) ◽

pp. 1511-1549 ◽

Cited By ~ 4

Author(s):

Jessica S. Helm ◽

Ruthann A. Rudel

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Dna Damage ◽

Ionizing Radiation ◽

Genomic Instability ◽

Hormonal Regulation ◽

Adverse Outcome ◽

Adverse Outcome Pathways

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Developing adverse outcome pathways on silver nanoparticle-induced reproductive toxicity via oxidative stress in the nematode Caenorhabditis elegans using a Bayesian network model

Nanotoxicology ◽

10.1080/17435390.2018.1529835 ◽

2018 ◽

Vol 12 (10) ◽

pp. 1182-1197 ◽

Cited By ~ 6

Author(s):

Jaeseong Jeong ◽

Taejun Song ◽

Nivedita Chatterjee ◽

Inhee Choi ◽

Yoon Kyung Cha ◽

...

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Bayesian Network ◽

Network Model ◽

Silver Nanoparticle ◽

Adverse Outcome ◽

Reproductive Toxicity ◽

Bayesian Network Model ◽

Nematode Caenorhabditis Elegans ◽

Adverse Outcome Pathways

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Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment

Environmental Toxicology and Chemistry ◽

10.1002/etc.60 ◽

2011 ◽

pp. n/a-n/a ◽

Cited By ~ 1

Author(s):

Gerald T. Ankley ◽

Richard S. Bennett ◽

Russell J. Erickson ◽

Dale J. Hoff ◽

Michael W. Hornung ◽

...

Keyword(s):

Risk Assessment ◽

Conceptual Framework ◽

Adverse Outcome ◽

Adverse Outcome Pathways

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The Dinitrophenol and Potassium Iodate Influence on Hordeum Vulgare Seedlings Viability\

Revista de Chimie ◽

10.37358/rc.18.8.6491 ◽

2018 ◽

Vol 69 (8) ◽

pp. 2160-2166

Author(s):

Elena Todirascu Ciornea ◽

Gabriela Dumitru ◽

Ion Sandu

Keyword(s):

Oxidative Stress ◽

Hordeum Vulgare ◽

Antioxidant Enzyme ◽

Oxygen Radicals ◽

Free Oxygen Radicals ◽

Potassium Iodate ◽

Free Oxygen ◽

Oxidative Stress Enzymes ◽

Stress Enzymes ◽

Seeds Germination

The using of the pesticides of dinitrophenol type in agriculture has as consequence the major pollution of the environment, the plants taking these substances from the soil and once with these ones they reach in the human and animal organism where they product disequilibrium that are interpreted through the accumulation of free oxygen radicals with direct repercussions on the antioxidant enzyme�s synthesis intensification and on their activity�s increase. The apply of treatments on the barley seeds had significant effects regarding the seeds� germination, the young plants� growth, the oxidative stress enzymes� activity, but also regarding the content of photoassimilators and carotenoids pigments.

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