API XML

Aop: 284

AOP Title

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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:

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Oxidative stress in chronic kidney disease

Graphical Representation

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Click to download graphical representation template

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Authors

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Paul Jennings

Point of Contact

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Frederic Y. Bois   (email point of contact)

Contributors

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  • Frederic Y. Bois

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite


This AOP was last modified on February 18, 2019 10:02

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Revision dates for related pages

Page Revision Date/Time
Binding, Thiol/seleno-proteins involved in protection against oxidative stress October 13, 2018 05:00
Oxidation, Glutathione (To be considered with MIE) November 09, 2017 06:40
Decreased protection against oxidative stress October 11, 2018 03:06
Oxidative Stress December 06, 2018 11:35
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

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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.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 1487 Binding, Thiol/seleno-proteins involved in protection against oxidative stress Binding, SH/SeH proteins involved in protection against oxidative stress
2 KE 926 Oxidation, Glutathione (To be considered with MIE) Oxidation, Glutathione
3 KE 1538 Decreased protection against oxidative stress Protection against oxidative stress, decreased
4 KE 1392 Oxidative Stress Oxidative Stress
5 KE 178 Disruption, Mitochondrial electron transport chain Disruption, Mitochondrial electron transport chain
6 KE 768 Increase, Cytotoxicity Increase, Cytotoxicity
7 AO 1603 Chronic kidney disease Chronic kidney disease

Relationships Between Two Key Events
(Including MIEs and AOs)

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Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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