API

Relationship: 1846

Title

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ROS generation leads to Oxidation/denatuation of membrane proteins

Upstream event

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ROS generation

Downstream event

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Oxidation/denatuation of membrane proteins

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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Some photoactivated chemicals can generate reactive oxygen species (ROS) after photoactivation of chemicals by irradiation of light (290–700 nm).  ROS generated from photoactivated chemicals can react with membrane proteins and lead to oxidation/denaturation of membrane proteins.

Evidence Supporting this KER

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Biological Plausibility

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Photoactivated chemicals by UVA generate ROS including singlet oxygen, superoxide, and hydroxyl radicals, and the generated ROS cause cross-linking of proteins and denaturation of proteins as oxidative damages by photoactivated chemicals (Dalle Carbonare and Pathak, 1992).

Empirical Evidence

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ROS generated from photosensitizing agents led to oxidation and denaturation of proteins, resulting in cross-linking of proteins and oxidation of sulfydryl groups (Dalle Carbonare and Pathak, 1992).

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 absorb photon energy from light within the range of 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.