Oxidative Stress in Cancer Research Lipid Peroxidation Detection Tools for Cancer Research

Lipid peroxidation (LPO) is one of the several degradation processes of lipids under oxidative stress. Primary products in LPO are lipid radicals and there are two major initiators to induce LPO process.

LPO process (1): Pro-oxidants

For pro-oxidant-induced LPO, lipids containing unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), are attacked by pro-oxidants including reactive oxygen species (ROS) and form lipid derived radicals. Lipid radical (L・) can be easily oxidized to lipid peroxyl radical (LOO・). Unstable LOO・ immediately extracts a hydrogen from another lipid molecule generating a lipid hydroperoxide (LOOH) and a new lipid radical (L・).

LPO process (2): Lipid oxidative enzymes

Once lipid radical is produced by the above two processes, lipid radicals expand the radical chain reaction (radical propagation step). In the termination reaction, antioxidants donate a hydrogen atom to the lipid peroxy radical (LOO・ ) species resulting in the formation of many different aldehydes including malondialdehyde (MDA), acrolein, propanal, hexanal, and 4-hydroxynonenal (4-HNE). These aldehydes are cytotoxic because reactive aldehydes attack biomolecules (proteins, DNA/RNA etc.) to form secondary products. These reactive aldehydes are considered as causative factors of organ injury, ferroptosis and ER stress.

Lipid peroxidation (LPO) is an oxidative degradation reaction of lipids triggered by oxidative stress. Lipid peroxidation is a well-established mechanism of cytotoxicity in living organisms and is used as an indicator of oxidative stress in cells and tissues.

Lipid peroxides are unstable and break down to form a complex series of compounds, including reactive carbonyl compounds. Polyunsaturated fatty acid (PUFA) peroxides produce malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) upon degradation, and these downstream compounds are known to cause a variety of effects including ER stress, cytotoxicity, and induction of feroroptosis. The measurements of MDA and HAE are conventionally used as indicators of lipid peroxidation. However, because of insufficient specificity and the production of a variety of downstream factors, novel method for measuring more upstream factors has been expected.

To understand the molecular mechanism and physiological relevance of LPO, detection and quantification methods for lipid radicals are required. The conventional detection methods for lipid radicals are highly limited. For example electron spin resonance (ESR) is a major strategy to detect radical products but not applied to cell based applications.
LipiRADICAL Green is the world's first detection reagents for lipid radicals, which are upstream factor of lipid-peroxidation (LPO). This product is a green fluorescent dye NBD-conjugated nitroxyl radical-derivative and well validated to selectively detect lipid radicals, not reactive oxygen radicals. This reagent is compatible with live cell imaging, structural analysis of lipid radicals by fluorescent LC/MS-MS and etc. LipiRADICAL Green is an innovative and powerful tool for LPO research.
A related product, OH-Pen inhibits lipid radicals specifically and will not react with other reactive oxygen species. It has similar structure to LipiRADICAL Green; NBD in LipiRADICAL Green was just converted to hydroxyl group. OH-PEN is also a powerful tools to research LPO.

For more detail about "LipiRADICAL Green" and "OH-PEN", please click here.