This AOP is licensed under the BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
AOP: 284
Title
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress leads to chronic kidney disease
Short name
Graphical Representation
Point of Contact
Contributors
- Frederic Y. Bois
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
This AOP was last modified on April 29, 2023 16:03
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Binding, Thiol/seleno-proteins involved in protection against oxidative stress | July 15, 2022 09:18 |
Oxidation, Glutathione (To be considered with MIE) | November 09, 2017 06:40 |
Decreased protection against oxidative stress | July 15, 2022 09:28 |
Oxidative Stress | August 26, 2024 10:26 |
Disruption, Mitochondrial electron transport chain | September 16, 2017 10:14 |
Increase, Cytotoxicity | September 16, 2017 10:16 |
Chronic kidney disease | February 18, 2019 09:58 |
Abstract
This AOP links thiol oxidation to CKD via oxidative and mitochondrial stress. Within the nephron, the proximal tubule is especially susceptible to injury from oxidative chemicals, as they can cause mitochondrial damage, which in turn can result in impairment of active and secondary transport, as well as in cell death. CKD is characterized by a progressive loss of renal function, the onset of which is initiated and/or accelerated by other factors such as diabetes, high blood pressure or exposure to nephrotoxic chemicals. Given its high energy demand for active transport, the proximal tubule is especially susceptible to injury from oxidative chemicals and mitotoxins.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1487 | Binding, Thiol/seleno-proteins involved in protection against oxidative stress | Binding, SH/SeH proteins involved in protection against oxidative stress |
KE | 926 | Oxidation, Glutathione (To be considered with MIE) | Oxidation, Glutathione |
KE | 1538 | Decreased protection against oxidative stress | Protection against oxidative stress, decreased |
KE | 1392 | Oxidative Stress | Oxidative Stress |
KE | 178 | Disruption, Mitochondrial electron transport chain | Disruption, Mitochondrial electron transport chain |
KE | 768 | Increase, Cytotoxicity | Increase, Cytotoxicity |
AO | 1603 | Chronic kidney disease | Chronic kidney disease |