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Protection against oxidative stress, decreased leads to Oxidative Stress
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory||adjacent||High||High||Marie-Gabrielle Zurich (send email)||Under development: Not open for comment. Do not cite||EAGMST Approved|
Life Stage Applicability
|All life stages||High|
Key Event Relationship Description
High levels of oxidizing free radicals can be very damaging to cells and molecules within the cell. As a result, the cell has important defense mechanisms to protect itself from ROS, including reducing agents, glutathione peroxidases, thioredoxin reductases. Oxidative stress is defined as an imbalance in the production of reactive oxygen species (ROS) and antioxidant defenses. Ensuing from this definition, a decrease in cellular antioxidant protection will lead to the increase of oxidative stress.
Evidence Supporting this KER
The cell has important defense mechanisms to protect itself from oxidative stress. The cellular defense mechanisms are numerous and include repair mechanisms, prevention mechanisms, physical defenses, as well as antioxidant defense such as antioxidant enzymes, low-molecular-weight antioxidants and chelating agents (Kohen, 2002). Whenever one or many of these mechanisms are decreased, the balance will tilt towards the production of ROS, and thus generate oxidative stress. In this KER we focus on the decreased protection due to interference with the antioxidant defense system.
Uncertainties and Inconsistencies
No uncertainties, since a decrease in protection against oxidative stress leads, by definition, to an increase in oxidative stress
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
The link between decrease in antioxidant protection and induction of oxidative stress can be found in Zebrafish, rodents (mouse and rat) and in man, but may not be restricted to these species.
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Meinerz, D.F. et al. (2011) Protective effects of organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions. Braz J Med Biol Res 44, 1156-1163.
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Rush, T. et al. (2012) Glutathione-mediated neuroprotection against methylmercury neurotoxicity in cortical culture is dependent on MRP1. Neurotoxicology 33, 476-481.
Usuki, F. et al. (2011) Post-transcriptional defects of antioxidant selenoenzymes cause oxidative stress under methylmercury exposure. J Biol Chem 286, 6641-6649.
Zhao, M et al. (2017) Effect of acrylamide-induced neurotoxicity in a primary astrocytes/microglial co-culture model. Toxicol in Vitro 39, 119-125.