Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events

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Authors

TANABE Shihori O’BRIEN Jason TOLLEFSEN Knut Erik KIM Youngjun CHAUHAN Vinita YAUK Carole HULIGANGA Elizabeth RUDEL Ruthann A. KAY Jennifer E. HELM Jessica S. BEATON Danielle FILIPOVSKA Julija SOVADINOVÁ Iva GARCIA-REYERO Natalia MALLY Angela POULSEN Sarah Sos DELRUE Nathalie FRITSCHE Ellen LUETTICH Karsta CINZIA La Rocca YEPISKOPOSYAN Hasmik KLOSE Joerdis DANIELSEN Pernille Hogh ESTERHUIZEN Maranda JACOBSEN Nicklas Raun VOGEL Ulla GANT Timothy W CHOI Ian FITZGERALD Rex

Year of publication 2022
Type Article in Periodical
Magazine / Source Frontiers in Toxicology
MU Faculty or unit

Faculty of Science

Citation
Web https://doi.org/10.3389/ftox.2022.887135
Doi http://dx.doi.org/10.3389/ftox.2022.887135
Keywords adverse outcome pathway (AOP); oxidative stress; reactive nitrogen species (RNS); disease; reactive oxygen species (ROS)
Attached files
Description Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named "Mystery or ROS" to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.
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