Aop:138

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Status

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

https://aopwiki.org/aops/138


AOP Title

Organic anion transporter (OAT1) inhibition leading to renal failure and mortality
Short name: OAT1 inhibition

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
organic anion transporter 1 (OAT1), Inhibition

Key Events

Event Support for Essentiality
blood uric acid concentration, Increased Strong
renal proximal tubular necrosis, Occurrence Moderate
blood potassium concentration, Increased Strong
tophi (urate) deposition, Occurrence Moderate
cardiac arrhythmia, Occurrence Moderate
Oxidative Stress, Increased

Adverse Outcome

Adverse Outcome
Mortality, Increased
Population, Decline

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
organic anion transporter 1 (OAT1), Inhibition Directly Leads to blood uric acid concentration, Increased Strong Strong
blood uric acid concentration, Increased Directly Leads to tophi (urate) deposition, Occurrence Strong Strong
tophi (urate) deposition, Occurrence Indirectly Leads to renal proximal tubular necrosis, Occurrence Moderate
renal proximal tubular necrosis, Occurrence Directly Leads to blood potassium concentration, Increased Moderate
blood potassium concentration, Increased Directly Leads to cardiac arrhythmia, Occurrence
cardiac arrhythmia, Occurrence Directly Leads to Mortality, Increased
renal proximal tubular necrosis, Occurrence Directly Leads to blood uric acid concentration, Increased
blood uric acid concentration, Increased Indirectly Leads to Oxidative Stress, Increased
Oxidative Stress, Increased Indirectly Leads to renal proximal tubular necrosis, Occurrence

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Life Stage Applicability

Life Stage Evidence Links
Adult Strong

Taxonomic Applicability

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

Sex Applicability

Sex Evidence Links
Male
Female

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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

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References