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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||Brendan Ferreri-Hanberry (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 Do not cite||EAGMST Approved|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 Collection Strategy
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.
Acaroz, U. et al. (2018) The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food Chem Toxicol 118, 745-752.
Agrawal, S. et al. (2015) Changes in tissue oxidative stress, brain biogenic amines and acetylcholinesterase following co-exposure to lead, arsenic and mercury in rats. Food Chem Toxicol 86, 208-216.
Alturfan, A.A. et al. (2012) Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep 39, 4589-4596.
Branco, V. et al. (2017) Impaired cross-talk between the thioredoxin and glutathione systems is related to ASK-1 mediated apoptosis in neuronal cells exposed to mercury. Redox Biol 13, 278-287.
Deepmala, J. et al. (2013) Protective effect of combined therapy with dithiothreitol, zinc and selenium protects acute mercury induced oxidative injury in rats. J Trace Elem Med Biol 27, 249-256.
Farina, M. et al. (2009) Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol Sci 112, 416-426.
Franco, J.L. et al. (2009) Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radic Biol Med 47, 449-457.
Fujimura, M., Usuki, F. (2017) In situ different antioxidative systems contribute to the site-specific methylmercury neurotoxicity in mice. Toxicology 392, 55-63.
Glaser, V. et al. (2013) Protective effects of diphenyl diselenide in a mouse model of brain toxicity. Chem Biol Interact 206, 18-26.
Joshi, D. et al. (2014) Reversal of methylmercury-induced oxidative stress, lipid peroxidation, and DNA damage by the treatment of N-acetyl cysteine: a protective approach. J Environ Pathol Toxicol Oncol 33, 167-182.
Kohen, R., Nyska, A. (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30, 620-650.
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.
Pan, X., et al. (2015) Melatonin attenuates oxidative damage induced by acrylamide invitro and in vivo. Ox. Med. Cell Longevity Vol 2015, Article ID 703709.
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.