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AOP Report: Glutathione Conjugation Leading to Reproductive Dysfunction via Oxidative Stress.
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- Author(s): Vieira, Leonardo R.1,2 (AUTHOR); Souza, Terezinha2 (AUTHOR); Farias, Davi F.1,2 (AUTHOR)
- Source:
Environmental Toxicology & Chemistry. Dec2023, Vol. 42 Issue 12, p2519-2528. 10p.- Subject Terms:
- Source:
- Additional Information
- Subject Terms:
- Abstract: We propose an adverse outcome pathway (AOP) for reproductive dysfunction via oxidative stress (OS). The AOP was developed based on Organisation for Economic Co‐operation and Development (OECD) Guidance Document 184 and on the specific considerations of the OECD users' handbook supplement to the guidance document for developing and assessing AOPs (no. 233). According to the qualitative and quantitative experimental data evaluation, glutathione (GSH) conjugation is the first upstream key event (KE) of this AOP to reproductive dysfunction triggering OS. This event causes depletion of GSH basal levels (KE2). Consequently, this drop of free GSH induces an increase of reactive oxygen species (KE3) generated by the natural cellular metabolic processes (cellular respiration) of the organism. Increased levels of these reactive species, in turn, induce an increase of lipid peroxidation (KE4). This KE consequently leads to a rise in the amount of toxic substances, such as malondialdehyde and hydroxynonenal, which are associated with decreased quality and competence of gamete cell division, consequently impairing fertility (KE5 and adverse outcome). The overall assessment of the general biological plausibility, the empirical support, and the essentiality of KE relationships was considered as high for this AOP. We conclude that GSH conjugation is able to lead to reproductive disorder in fishes and mammals, via OS, but that the amount of stressor needed to trigger the AOP differs between stressors. Environ Toxicol Chem 2023;42:2519–2528. © 2023 SETAC [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Environmental Toxicology & Chemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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