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Key Event: 1445

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, Lipid peroxidation

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Increase, LPO

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
cell

Organ term

Organ term
organ

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
lipid oxidation	polyunsaturated fatty acid	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status
Excessive ROS leading to mortality (3)	KeyEvent	You Song (send email)	Under development: Not open for comment. Do not cite
Oxidation of Reduced Glutathione Leading to Mortality	KeyEvent	Carmel Mothersill (send email)	Open for citation & comment
Glutathione conjugation leading to reproductive dysfunction	KeyEvent	Leonardo Vieira (send email)	Under Development: Contributions and Comments Welcome
Essential element imbalance leads to reproductive failure via oxidative stress	KeyEvent	Travis Karschnik (send email)	Under development: Not open for comment. Do not cite
ROS leading to growth inhibition via LPO and cell death	KeyEvent	You Song (send email)	Under development: Not open for comment. Do not cite
Keap1 cysteine oxidation,liver failure	KeyEvent	Young Jun Kim (send email)	Under development: Not open for comment. Do not cite
ROS leading to growth inhibition via LPO and decreased cell proliferation	KeyEvent	You Song (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
fish	fish	Moderate	NCBI
mammals	mammals	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Lipid peroxidation is an oxidative degradation process affecting lipids, particularly polyunsaturated fatty acids in cellular and organelle membranes. The process is initiated when oxidants, including free radicals and reactive oxygen species, abstract hydrogen atoms from susceptible lipid chains. This generates lipid radicals that react with molecular oxygen to form lipid peroxyl radicals and lipid hydroperoxides. These products can propagate chain reactions, producing additional oxidized lipids and secondary reactive aldehydes such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and related hydroxyalkenals (Esterbauer et al., 1991; Yin et al., 2011; Ayala et al., 2014).

As a key event, increased lipid peroxidation represents a measurable increase in oxidized lipid products relative to an appropriate control state. The event may reflect direct oxidative damage to membrane lipids, increased formation of lipid hydroperoxides, increased accumulation of MDA or 4-HNE, or increased abundance of specific oxidized phospholipid or fatty acid species. Because lipid peroxidation products can alter membrane fluidity, permeability and signaling, the event is relevant both as a marker of oxidative damage and as a potential contributor to downstream mitochondrial dysfunction, loss of membrane integrity, cytotoxicity and impaired growth (Esterbauer et al., 1991; Uchida, 2003; Ayala et al., 2014).

This KE should be described independently of any specific upstream or downstream event. In an AOP context, lipid peroxidation is commonly downstream of oxidative stress and upstream of events related to decreased mitochondrial coupling, cellular injury, or altered membrane-dependent biological processes. However, the KE itself is defined only by the increased lipid oxidation state and its measurable biochemical products.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

No OECD Test Guideline is currently dedicated specifically to measurement of lipid peroxidation as a standalone endpoint. Nevertheless, the KE can be measured using several well-established biochemical and analytical methods. Scientific confidence is highest when methods quantify specific lipid peroxidation products or oxidized lipid species directly, and lower when nonspecific colorimetric assays are used without appropriate controls or confirmatory methods.

Measurement approach	Endpoint measured	Representative method names	Scientific confidence and limitations
TBARS / MDA assays	Thiobarbituric acid reactive substances, often interpreted as MDA or MDA-like products	TBARS assay; spectrophotometric or fluorometric MDA assays	Widely used and sensitive, but not fully specific because TBA can react with compounds other than MDA. Best used as a screening or comparative indicator of lipid peroxidation, particularly when supported by extraction, HPLC separation or additional markers (Buege and Aust, 1978; Ohkawa et al., 1979; Janero, 1990; Draper and Hadley, 1990).
4-HNE and hydroxyalkenal assays	4-hydroxy-2-nonenal and related reactive aldehydes	ELISA, immunoblotting of HNE-protein adducts, HPLC or LC-MS quantification	Mechanistically informative because 4-HNE is a major bioactive lipid peroxidation product. Antibody-based methods can detect protein adducts, whereas chromatographic or mass spectrometric methods improve specificity (Esterbauer et al., 1991; Uchida, 2003; Ayala et al., 2014).
Lipid hydroperoxide assays	Primary lipid hydroperoxides	FOX assay; iodometric assays; commercial lipid hydroperoxide kits	Useful for detecting relatively early lipid peroxidation products. Hydroperoxides can be unstable and sample handling is critical. FOX-based methods provide a simple approach for lipid hydroperoxide detection (Jiang et al., 1992).
Chromatography and mass spectrometry	Specific oxidized fatty acids, oxidized phospholipids, oxylipins or oxidized lipid classes	HPLC, GC, LC-MS/MS, lipidomics	High specificity and quantitative power when standards and validated workflows are available. These methods can distinguish individual oxidized lipid species and are preferred for detailed mechanistic studies (Yin et al., 2011; Li et al., 2019).
Fluorescent probes and imaging	Oxidation-sensitive fluorescent signal in cellular lipids	BODIPY 581/591 C11 and related lipid oxidation probes	Useful for cell-based or imaging applications and spatial localization, but probe specificity, photoxidation and calibration must be considered. Best used with complementary biochemical or analytical endpoints.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

The biological domain of applicability for this KE is broad because lipid membranes and oxidizable fatty acids are widely conserved biological features. The event is applicable wherever lipid substrates susceptible to oxidation are present and where oxidants can access those substrates. The KE is therefore relevant across many biological systems, including unicellular algae, invertebrates, fish, mammals and human-derived cells. The current evidence base is strongest in mammalian systems because lipid peroxidation chemistry and analytical methods have been extensively studied there, but ecotoxicological evidence supports relevance in algae, crustaceans, mollusks and fish.

The KE is not intrinsically limited by sex or life stage. However, the magnitude of lipid peroxidation and its downstream consequences may be modified by lipid composition, antioxidant capacity, oxygen availability, temperature, metabolic rate, nutritional status, metal availability, and exposure duration. Organisms or tissues enriched in polyunsaturated fatty acids, exposed to high oxygen flux, or experiencing antioxidant depletion may be particularly susceptible. In photosynthetic organisms, lipid peroxidation may also occur in chloroplast and thylakoid membranes; in animals, mitochondria and plasma membranes are common sites of interest.

Within the ROS-growth AOP network, this KE is especially relevant as a molecular damage event linking oxidative stress to impaired mitochondrial membrane function, decreased coupling of oxidative phosphorylation, reduced ATP production, cell injury, and decreased growth. Nevertheless, this KE should remain modular: it may be reused in other AOPs whenever increased lipid oxidation products are measured as a consequence of oxidative stress or other lipid-damaging perturbations.

References

List of the literature that was cited for this KE description. More help

AOP-Wiki. 2026. Key Event 1445: Increase, Lipid peroxidation. AOP-Wiki. Available at: https://aopwiki.org/events/1445. Accessed 14 May 2026.

Alam MR, Ehiguese FO, Vitale D, Martín-Díaz ML. 2022. Oxidative stress response to hydrogen peroxide exposure of Mytilus galloprovincialis and Ruditapes philippinarum: reduced embryogenesis success and altered biochemical response of sentinel marine bivalve species. Environmental Chemistry and Ecotoxicology 4:97-105.

Ayala A, Munoz MF, Arguelles S. 2014. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity 2014:360438. https://doi.org/10.1155/2014/360438.

Belaid C, Sbartai I. 2021. Assessing the effects of Thiram to oxidative stress responses in a freshwater bioindicator cladoceran (Daphnia magna). Chemosphere 268:128808. https://doi.org/10.1016/j.chemosphere.2020.128808.

Buege JA, Aust SD. 1978. Microsomal lipid peroxidation. Methods in Enzymology 52:302-310. https://doi.org/10.1016/S0076-6879(78)52032-6.

Cong B, Liu C, Wang L, Chai Y. 2020. The impact on antioxidant enzyme activity and related gene expression following adult zebrafish (Danio rerio) exposure to dimethyl phthalate. Animals 10(4):717. https://doi.org/10.3390/ani10040717.

Draper HH, Hadley M. 1990. Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology 186:421-431. https://doi.org/10.1016/0076-6879(90)86135-I.

Esperanza M, Cid A, Herrero C, Rioboo C. 2015. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: screening cytotoxicity and genotoxicity endpoints. Aquatic Toxicology 165:210-221. https://doi.org/10.1016/j.aquatox.2015.06.004.

Esterbauer H, Schaur RJ, Zollner H. 1991. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology and Medicine 11(1):81-128. https://doi.org/10.1016/0891-5849(91)90192-6.

Janero DR. 1990. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radical Biology and Medicine 9(6):515-540. https://doi.org/10.1016/0891-5849(90)90131-2.

Jiang ZY, Hunt JV, Wolff SP. 1992. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Analytical Biochemistry 202(2):384-389. https://doi.org/10.1016/0003-2697(92)90122-N.

Knauert S, Knauer K. 2008. The role of reactive oxygen species in copper toxicity to two freshwater green algae. Journal of Phycology 44(2):311-319. https://doi.org/10.1111/j.1529-8817.2008.00471.x.

Li L, Zhong S, Shen X, Li Q, Xu W, Tao Y, Yin H. 2019. Recent development on liquid chromatography-mass spectrometry analysis of oxidized lipids. Free Radical Biology and Medicine 144:16-34. https://doi.org/10.1016/j.freeradbiomed.2019.06.006.

Moore TD, Martin-Creuzburg D, Yampolsky LY. 2023. Diet effects on longevity, heat tolerance, lipid peroxidation and mitochondrial membrane potential in Daphnia. Oecologia 202(1):151-163. https://doi.org/10.1007/s00442-023-05382-1.

Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95(2):351-358. https://doi.org/10.1016/0003-2697(79)90738-3.

Ouillon N, Sokolov EP, Otto S, Rehder G, Sokolova IM. 2021. Effects of variable oxygen regimes on mitochondrial bioenergetics and reactive oxygen species production in a marine bivalve, Mya arenaria. Journal of Experimental Biology 224(4):jeb237156. https://doi.org/10.1242/jeb.237156.

Tseng YC, Chen RD, Lucassen M, Schmidt MM, Dringen R, Abele D, Hwang PP. 2011. Exploring uncoupling proteins and antioxidant mechanisms under acute cold exposure in brains of fish. PLoS ONE 6(3):e18180. https://doi.org/10.1371/journal.pone.0018180.

Uchida K. 2003. 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Progress in Lipid Research 42(4):318-343. https://doi.org/10.1016/S0163-7827(03)00014-6.

Yin H, Xu L, Porter NA. 2011. Free radical lipid peroxidation: mechanisms and analysis. Chemical Reviews 111(10):5944-5972. https://doi.org/10.1021/cr200084z.