Aop:130

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Status

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

https://aopwiki.org/aops/130


AOP Title

Phospholipase A inhibitors lead to hepatotoxicity
Short name: Phospholipase A inhibitors

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Status

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Project 1.39: The AOP on Phospholipase A inhibitors leading to hepatotoxicity

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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
Phospholipase A, Inhibition Strong

Key Events

Event Support for Essentiality
Lipid bilayer, Damage Strong
Lysosomal function, Disturbance Strong
Mitochondria, Injury Strong
Cytoplasmic vacuolization (hepatocyte), Occurrence Weak
Ballooning degeneration (hepatocyte), Occurrence Weak
Cytoplasmic vacuolization (kupffer cell), Occurrence Weak
Microvesicular fat, Induction Weak
Mallory body, Formation Weak
Cytoplasmic vacuolization (Bile duct cell), Occurrence Weak

Adverse Outcome

Adverse Outcome
Liver fibrosis, Formation

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Phospholipase A, Inhibition Directly Leads to Lipid bilayer, Damage Strong
Phospholipase A, Inhibition Directly Leads to Lysosomal function, Disturbance Strong
Phospholipase A, Inhibition Directly Leads to Mitochondria, Injury Strong
Lipid bilayer, Damage Directly Leads to Cytoplasmic vacuolization (hepatocyte), Occurrence Weak
Lipid bilayer, Damage Directly Leads to Ballooning degeneration (hepatocyte), Occurrence Weak
Lipid bilayer, Damage Directly Leads to Cytoplasmic vacuolization (Bile duct cell), Occurrence Weak
Lipid bilayer, Damage Directly Leads to Cytoplasmic vacuolization (kupffer cell), Occurrence Weak
Lysosomal function, Disturbance Directly Leads to Cytoplasmic vacuolization (hepatocyte), Occurrence Weak
Lysosomal function, Disturbance Directly Leads to Ballooning degeneration (hepatocyte), Occurrence Weak
Lysosomal function, Disturbance Directly Leads to Cytoplasmic vacuolization (Bile duct cell), Occurrence Weak
Lysosomal function, Disturbance Directly Leads to Cytoplasmic vacuolization (kupffer cell), Occurrence Weak
Mitochondria, Injury Directly Leads to Cytoplasmic vacuolization (hepatocyte), Occurrence Weak
Mitochondria, Injury Directly Leads to Ballooning degeneration (hepatocyte), Occurrence Weak
Mitochondria, Injury Directly Leads to Cytoplasmic vacuolization (Bile duct cell), Occurrence Weak
Mitochondria, Injury Directly Leads to Cytoplasmic vacuolization (kupffer cell), Occurrence Weak
Cytoplasmic vacuolization (hepatocyte), Occurrence Directly Leads to Microvesicular fat, Induction Weak
Cytoplasmic vacuolization (hepatocyte), Occurrence Directly Leads to Mallory body, Formation Weak
Ballooning degeneration (hepatocyte), Occurrence Directly Leads to Microvesicular fat, Induction Weak
Ballooning degeneration (hepatocyte), Occurrence Directly Leads to Mallory body, Formation Weak
Cytoplasmic vacuolization (Bile duct cell), Occurrence Directly Leads to Microvesicular fat, Induction Weak
Cytoplasmic vacuolization (Bile duct cell), Occurrence Directly Leads to Mallory body, Formation Weak
Cytoplasmic vacuolization (kupffer cell), Occurrence Directly Leads to Microvesicular fat, Induction Weak
Cytoplasmic vacuolization (kupffer cell), Occurrence Directly Leads to Mallory body, Formation Weak
Microvesicular fat, Induction Directly Leads to Liver fibrosis, Formation Strong
Mallory body, Formation Directly Leads to Liver fibrosis, Formation Strong

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Life Stage Applicability

Life Stage Evidence Links
1 to < 3 months Strong
Adults Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
Sprague-Dawley Strong
Homo sapiens Homo sapiens Strong NCBI

Sex Applicability

Sex Evidence Links
Male Strong
Unspecific Weak

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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