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.
- Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Comm. 2017;482(3):419-425.
- Parthasarathy S, Raghavamenon A, Garelnabi MO, Santanam N. Oxidized low-density lipoprotein. Methods Mol Biol. 2010;610:403-417.
- Colas R, Pruneta-Deloche V, Guichardant M, et al. Increased lipid peroxidation in LDL from type-2 diabetic patients. Lipids. 2010;45(8):723-731.
- 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.
- Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016;73(11-12):2195-2209.
- Agmon E, Solon J, Bassereau P, Stockwell BR. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci Rep. 2018;8(1):5155.
- 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.
- Tualeka AR, Martiana T, Ahsan A, Russeng SS, Meidikayanti W. Association between Malondialdehyde and Glutathione (L-gamma-Glutamyl-Cysteinyl-Glycine/GSH) Levels on Workers Exposed to Benzene in Indonesia. Maced J Med Sci. 2019;7(7):1198-1202.
- Arribas L, Almansa I, Miranda M, Muriach M, Romero FJ, Villar VM. Serum Malondialdehyde Concentration and Glutathione Peroxidase Activity in a Longitudinal Study of Gestational Diabetes. PloS one. 2016;11(5):e0155353.
- Cordero MD, Cano-García FJ, Alcocer-Gómez E, De Miguel M, Sánchez-Alcázar JA. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q10 effect on clinical improvement. PloS one. 2012;7(4):e35677.
- Arab H, Mahjoub S, Hajian-Tilaki K, Moghadasi M. The effect of green tea consumption on oxidative stress markers and cognitive function in patients with Alzheimer’s disease: A prospective intervention study. Casp J Int Med. 2016;7(3):188-194.
- Kajarabille N, Latunde-Dada GO. Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators. Int J Mol Sci. 2019;20(19).
Elevated lipid peroxides indicate damage to lipids and lipid membranes.
The enzyme glutathione peroxidase is responsible for reducing lipid peroxides and uses glutathione as a cofactor.
Lower levels of glutathione may contribute to lipid peroxidation.
Vitamin E mitigates toxicity from lipid peroxides.
Coenzyme Q10 was shown to reduce lipid peroxides and symptoms in patients with fibromyalgia and headaches.
Green tea catechins decreased lipid peroxide concentrations in patients with Alzheimer’s disease.
Pre-clinical studies demonstrate inhibition of ferroptosis with iron chelators, polyphenols including curcumin, EGCG from green tea, baicalein, and lipophilic antioxidants including vitamin E.
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