Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Publisher Summary This chapter discusses the methods used for the qualitative and quantitative determination of aldehydes in biological systems. It focuses on 4-hydroxynonenal (HNE) and malondialdehyde (MDA). 4-Hydroxynonenal is produced as a major product of the peroxidative decomposition of polyunsaturated fatty acids (PUFA) and possesses cytotoxic, hepatotoxic, mutagenic, and genoroxic properties. Increased levels of HNE are found in plasma and various organs under conditions of oxidative stress. In addition to HNE, lipid peroxidation generates many other aldehydes that may also be of toxicological significance. Malondialdehyde is in many instances the most abundant individual aldehyde resulting from lipid peroxidation, and its determination by thiobarbituric acid (TBA) is one of the most common assays in lipid peroxidation studies. In vitro MDA can alter proteins, DNA, RNA, and many other biomolecules. Recently, it has been demonstrated with monoclonal antibodies that malonaldehyde-altered protein occurs in atheroma of hyperlipidemic rabbits.

Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal

Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury.

Recent studies have demonstrated that human spermatozoa are capable of generating reactive oxygen species and that this activity is significantly accelerated in cases of defective sperm function. In view of the pivotal role played by lipid peroxidation in mediating free radical damage to cells, we have examined the relationships between reactive oxygen species production, lipid peroxidation, and the functional competence of human spermatozoa. Using malondialdehyde production in the presence of ferrous ion promoter as an index of lipid peroxidation, we have shown that lipid peroxidation is significantly accelerated in populations of defective spermatozoa exhibiting high levels of reactive oxygen species production or in normal cells stimulated to produce oxygen radicals by the ionophore, A23187. The functional consequences of lipid peroxidation included a dose-dependent reduction in the ability of human spermatozoa to exhibit sperm oocyte-fusion, which could be reversed by the inclusion of a chain-breaking antioxidant, alpha-tocopherol. Low levels of lipid peroxidation also had a slight enhancing effect on the generation of reactive oxygen species in response to ionophore, without influencing the steady-state activity. At higher levels of lipid peroxidation, both the basal level of reactive oxygen species production and the response to A23187 were significantly diminished. In contrast, lipid peroxidation had a highly significant, enhancing effect on the ability of human spermatozoa to bind to both homologous and heterologous zonae pellucidae via mechanisms that could again be reversed by alpha-tocopherol. These results are consistent with a causative role for lipid peroxidation in the etiology of defective sperm function and also suggest a possible physiological role for the reactive oxygen species generated by human spermatozoa in mediating sperm-zona interaction.

Generation of reactive oxygen species, lipid peroxidation, and human sperm function.

Biomarkers of free radical damage: Applications in experimental animals and in humans

The nature and mechanism of formation of the thiobarbituric acid (TBA)-reactive material produced in the autoxidation of polyunsaturated fatty acids (PUFA) or their esters has been studied. On the basis of chemical studies and

Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA-reactive materials from prostaglandin-like endoperoxides.

E. Blair

Papers

Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA-reactive materials from prostaglandin-like endoperoxides.