Aop:177

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/177


AOP Title

Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality
Short name: Cox1 inhibition renal failure

Authors

Kellie Fay

Status

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Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

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Abstract

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Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Cyclooxygenase 1 activity, Inhibition Moderate

Key Events

Event Support for Essentiality
Prostaglandin F2alpha concentration, plasma , Decreased
renal ischemia, Occurrence
renal proximal tubular necrosis, Occurrence
blood potassium concentration, Increased
cardiac arrhythmia, Occurrence
Oxidative Stress, Increased
blood uric acid concentration, Increased
tophi (urate) deposition, Occurrence

Adverse Outcome

Adverse Outcome
Mortality, Increased
Population, Decline

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Prostaglandin F2alpha concentration, plasma , Decreased Indirectly Leads to renal ischemia, Occurrence Weak
renal proximal tubular necrosis, Occurrence Directly Leads to blood potassium concentration, Increased Strong
Cyclooxygenase 1 activity, Inhibition Directly Leads to Prostaglandin F2alpha concentration, plasma , Decreased
blood potassium concentration, Increased Directly Leads to cardiac arrhythmia, Occurrence
cardiac arrhythmia, Occurrence Directly Leads to Mortality, Increased
renal ischemia, Occurrence Indirectly Leads to Oxidative Stress, Increased
Oxidative Stress, Increased Indirectly Leads to renal proximal tubular necrosis, Occurrence
renal proximal tubular necrosis, Occurrence Directly Leads to blood uric acid concentration, Increased Strong
blood uric acid concentration, Increased Directly Leads to tophi (urate) deposition, Occurrence Strong
tophi (urate) deposition, Occurrence Indirectly Leads to renal proximal tubular necrosis, Occurrence
blood uric acid concentration, Increased Indirectly Leads to Oxidative Stress, Increased

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Life Stage Applicability

Life Stage Evidence Links
Adult Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
Gyps coprotheres Gyps coprotheres Strong NCBI
Gyps rueppelli Gyps rueppellii Moderate NCBI
Gyps fulvus Gyps fulvus Strong NCBI
Gyps himalayensis Moderate NCBI
Gyps bengalensis Gyps bengalensis Strong NCBI
Gyps africanus Gyps africanus Strong NCBI
Gyps indicus Gyps indicus Strong NCBI
Gallus gallus Gallus gallus Strong NCBI
Aegypius monachus Aegypius monachus Moderate NCBI

Sex Applicability

Sex Evidence Links
Male Strong
Female Strong

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

References