API

Relationship: 1850

Title

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Oxidation of membrane lipids leads to Inflammatory events

Upstream event

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Oxidation of membrane lipids

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

Evidence Supporting this KER

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Biological Plausibility

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Lipid peroxidation in cellar membrane is an oxidative damage of cellular membrane, and viability of cells decreases by lipid peroxidation of photoreactive chemicals (Castell et al., 1994).

Empirical Evidence

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Increases in lipid peroxidation and inflammatory-related cytokines were observed in the murine skin, and naringenin, an anti-oxidant, attenuated these increases in a dose-dependent manner (Martinez et al., 2015).

Benzoyl peroxide, a ROS generator, led to lipid peroxidation and GSH depletion, and the changes caused the gene expression of pro-inflammatory cytokines in human keratinocytes (Valacchi et al., 2001).

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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Castell JV, Gomez-Lechon MJ, Grassa C, Martinez LA, Miranda MA, Tarrega P. Photodynamic lipid peroxidation by the photosensitizing nonsteroidal antiinflammatory drugs suprofen and tiaprofenic acid. Photochem Photobiol. 1994;59:35-9.

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.

Martinez RM, Pinho-Ribeiro FA, Steffen VS, Caviglione CV, Vignoli JA, Barbosa DS, et al. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice. Journal of natural products. 2015;78:1647-55.

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

Valacchi G, Rimbach G, Saliou C, Weber SU, Packer L. Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes. Toxicology. 2001;165:225-34.