API

Relationship: 1851

Title

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Oxidation/denatuation of membrane proteins leads to Inflammatory events

Upstream event

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Oxidation/denatuation of membrane proteins

Downstream event

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Inflammatory events

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Reactive oxygen species generated from photoreactive chemicals leading to phototoxic reactions adjacent High Low

Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Sex Applicability

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Sex Evidence
Mixed High

Life Stage Applicability

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Term Evidence
All life stages High

Key Event Relationship Description

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Oxidation/denaturation of membrane proteins can lead to inflammatory events via oxidative damage of cellular membranes and increases in expression of pro-inflammatory cytokines. 

Necrosis in living tissues can be occurred as an inflammatory events via oxidative damages of membrane proteins.

Evidence Supporting this KER

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Biological Plausibility

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Oxidative damage of membrane proteins by photoactivated chemicals can cause oxidation and denaturation of proteins, and damaged proteins induces inflammatory events (necrosis) (Dalle Carbonare and Pathak, 1992, Opie, 1962).

Empirical Evidence

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Denaturation of proteins induced necrosis and inflammatory in the skin (Opie, 1962).

Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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Chemicals: This KER applies to a wide range of chemicals.  The chemicals generate ROS under exposure to light (290-700 nm) (ICH, 2014, Onoue and Tsuda, 2006).

Sex: This KER applies to both males and females. 

Life stages: The relevant life stages for this KER are all life stages after born.

Taxonomic: This KER mainly applies to human.

References

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Dalle Carbonare M, Pathak MA. Skin photosensitizing agents and the role of reactive oxygen species in photoaging. J Photochem Photobiol B. 1992;14:105-24.

ICH. ICH Guideline S10 Guidance on Photosafety Evaluation of Pharmaceuticals.: International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2014.

Onoue S, Tsuda Y. Analytical studies on the prediction of photosensitive/phototoxic potential of pharmaceutical substances. Pharmaceutical research. 2006;23:156-64.

Opie EL. On the relation of necrosis and inflammation to denaturation of proteins. The Journal of experimental medicine. 1962;115:597-608.