Lipid Peroxides

Lipid peroxides are a class of reactive oxygen species (ROS) that preferentially oxidize polyunsaturated fatty acids (PUFAs) linoleic, arachidonic, and docosahexaenoic acids (omega-6 PUFAs).

Lipid peroxides exert their toxic effects via two mechanisms. One is by altering the assembly, composition, structure and dynamics of cell membrane lipid bilayers. The second is by producing more reactive oxygen species or by degrading into reactive compounds capable of damaging DNA and proteins.

The central nervous system is particularly prone to lipid peroxidation due to the high quantity of ROS as a byproduct of ATP synthesis in a lipid-enriched environment.16 Circulating LDLs can be affected by lipid peroxidation and are implicated in diseases including atherosclerosis, metabolic syndrome, and diabetes.

Genova uses the TBARS (thiobarbituric acid reactive substances) approach for determination of lipid peroxidation; the main indicator of which is malondialdehyde (MDA). MDA is a degradation product of lipid peroxides. Ferroptosis is an iron-dependent form of cell death that is characterized by the accumulation of lipid peroxides. It is distinct from other cell death modalities, including apoptosis, classic necrosis, autophagy, and others.

Synthesis of PUFAs and their incorporation into phospholipid membranes is required for ferroptosis. This process is triggered by the loss of glutathione peroxidase 4 (GPX4), a lipid repair enzyme. Depriving cells of cysteine, an amino acid precursor of glutathione can also induce ferroptosis. Clinically, ferroptosis has been associated with degenerative diseases (Alzheimer’s, Huntington’s, and Parkinson’s diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration.

References:

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- Colas R, Sassolas A, Guichardant M, et al. LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets. Diabetologia. 2011;54(11):2931-2940.

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- Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017;171(2):273-285.

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- Kajarabille N, Latunde-Dada GO. Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators. Int J Mol Sci. 2019;20(19).