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Oxidative Stress leads to Increase, Inflammation
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway||adjacent||High||Low||John Frisch (send email)||Under development: Not open for comment. Do not cite|
Life Stage Applicability
|All life stages||High|
Key Event Relationship Description
Inflammation is one consequence of oxidative stress. Inflammation can be characterized as a multi-step process (Villeneuve et al. 2018): 1. Activation of tissue cells due to stress; 2. Increases in proinflammatory mediator (ex. cytokines); 3. Leukocyte recruitment; 4. Inflammatory response.
Evidence Collection Strategy
This KER was identified as part of an Environmental Protection Agency effort to represent putative AOPs from peer-reviewed literature which were heretofore unrepresented in the AOP-Wiki. Support for this KER is referenced in publications cited in the originating work of Jeong and Choi (2020).
Evidence Supporting this KER
The biological plausibility linking inflammation to oxidative stress is strong. Oxidative stress triggers cellular signals, mediated by proinflammatory mediators such as cytokines, which initiates inflammation pathways. At the cellular level, there are increases in leukocyte recruitment; at the tissue and organ levels, visible inflammation occurs.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Life Stage: The life stage applicable to this key event relationship is all life stages.
Sex: This key event relationship applies to both males and females.
Taxonomic: This key event relationship appears to be present broadly, with representative studies including mammals (humans, lab mice, lab rats) and teleost fish.
Gamo, K., Kiryu-Seo, S., Konishi, H., Aoki, S., Matushima, K., Wada, K., and Kiyama, H. 2008. G-protein-coupled receptor screen reveals a role for chemokine recepteor CCR5 in suppressing microglial neurotoxicity. Journal of Neuroscience 28: 11980-11988.
Jin, Y., Xia, J., Pan, Z., Yang, J., Wang, W., and Fu, Z. 2018. Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafish. Environmental Pollution 235: 322-329.
Lei, L., Wu, S., Lu, S., Liu, M., Song, Y., Fu, Z., Shi, H., Raley-Susman, K.M., and He, D. 2018. Microplastic particles cause intestinal damage and other adverse effects in zebrafish Danio rerio and nematode Caenorhabditis elegans. Science of the Total Environment 619-620: 1-8.
Lu, Y., Zhang, Y., Dengy, Y., Jiang, W., Zhao, Y., Geng, J., Ding, L., Ren, H. 2016. Uptake and accumulation of polystyrene microplastics in zebrafish (Danio rerio) and toxic effects in liver. Environmental Science and Technology 50: 4054-4060.
Villeneuve, D.L., Landesmann, B., Allavena, P., Ashley, N., Bal-Price, A., Corsini, E., Halappanavar, S., Hussell, T., Laskin, D., Lawrence, T., Nikolic-Paterson, D., Pallary, M., Paini, A., Pietrs, R., Roth, R., and Tschudi-Monnet, F. 2018. Toxicological Sciences 346:352.
Wright, S.L. and Kelly, F.J. 2017. Plastic and human health: a micro issue? Enviromental Science and Technology 51: 6634-6647.