Lipid peroxidation derived reactive carbonyl species in free and conjugated forms as an index of lipid peroxidation: limits and perspectives

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Abstract

Reactive carbonyl species (RCS) formed by lipidperoxidation as free forms or as enzymatic and non-enzymatic conjugates are widely used as an index of oxidative stress. Besides general measurements based on derivatizing reactions, more selective and sensitive MS based analyses have been proposed in the last decade. Untargeted and targeted methods for the measurement of free RCS and adducts have been described and their applications to in vitro and ex vivo samples have permitted the identification of many biological targets, reaction mechanisms and adducted moieties with a particular relevance to RCS protein adducts. The growing interest in protein carbonylation can be explained by considering that protein adducts are now recognized as being involved in the damaging action of oxidative stress so that their measurement is performed not only to obtain an index of lipid peroxidation but also to gain a deeper insight into the molecular mechanisms of oxidative stress. The aim of the review is to discuss the most novel analytical approaches and their application for profiling reactive carbonyl species and their enzymatic and non-enzymatic metabolites as an index of lipid-oxidation and oxidative stress. Limits and perspectives will be discussed.

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Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges.

Dimitrios Tsikas (2017)

Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and the F2-isoprostane 15(S)-8-iso-prostaglandin F2α (15(S)-8-iso-PGF2α) are the best investigated products of lipid peroxidation. MDA, HNE and 15(S)-8-iso-PGF2α are produced from polyunsaturated fatty acids (PUFAs) both by chemical reactions and by reactions catalyzed by enzymes. 15(S)-8-iso-PGF2α and other F2-isoprostanes are derived exclusively from arachidonic acid (AA). The number of PUFAs that may contribute to MDA and HNE is much higher. MDA is the prototype of the so called thiobarbituric acid reactive substances (TBARS). MDA, HNE and 15(S)-8-iso-PGF2α are the most frequently measured biomarkers of oxidative stress, namely of lipid peroxidation. In many diseases, higher concentrations of MDA, HNE and 15(S)-8-iso-PGF2α are measured in biological samples as compared to health. Therefore, elevated oxidative stress is generally regarded as a pathological condition. Decreasing the concentration of biomarkers of oxidative stress by changing life style, by nutritional intake of antioxidants or by means of drugs is generally believed to be beneficial to health. Reliable assessment of oxidative stress by measuring MDA, HNE and 15(S)-8-iso-PGF2α in biological fluids is highly challenging for two important reasons: Because of the duality of oxidative stress, i.e., its origin from chemical and enzymatic reactions, and because of pre-analytical and analytical issues. This article focuses on these key issues. It reviews reported analytical methods and their principles for the quantitative measurement of MDA, HNE and 15(S)-8-iso-PGF2α in biological samples including plasma and urine, and critically discusses their biological and biomedical outcome which is rarely crystal clear and free of artefacts.

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Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine

Rafael Radi (2018)

Aerobic life in humans imposes the hazard of excess oxidation in cell and tissue components that may compromise cell function and viability. The formation and accumulation of oxidized products in biomolecules such as proteins and lipids are observed in various pathologies and during the normal aging process. This review article aims to integrate some early and remarkable discoveries in the field, with more recent developments that helped to define a causative role of oxygen radicals, nitric oxide, and peroxynitrite in human physiology and pathology. These aspects of human redox biochemistry contribute to the understanding of the molecular basis of diseases and aging and open avenues for the development of preventive and therapeutic strategies in molecular medicine. Oxygen-derived free radicals and related oxidants are ubiquitous and short-lived intermediates formed in aerobic organisms throughout life. These reactive species participate in redox reactions leading to oxidative modifications in biomolecules, among which proteins and lipids are preferential targets. Despite a broad array of enzymatic and nonenzymatic antioxidant systems in mammalian cells and microbes, excess oxidant formation causes accumulation of new products that may compromise cell function and structure leading to cell degeneration and death. Oxidative events are associated with pathological conditions and the process of normal aging. Notably, physiological levels of oxidants also modulate cellular functions via homeostatic redox-sensitive cell signaling cascades. On the other hand, nitric oxide ( • NO), a free radical and weak oxidant, represents a master physiological regulator via reversible interactions with heme proteins. The bioavailability and actions of • NO are modulated by its fast reaction with superoxide radical ( O 2 • − ), which yields an unusual and reactive peroxide, peroxynitrite, representing the merging of the oxygen radicals and • NO pathways. In this Inaugural Article, I summarize early and remarkable developments in free radical biochemistry and the later evolution of the field toward molecular medicine; this transition includes our contributions disclosing the relationship of • NO with redox intermediates and metabolism. The biochemical characterization, identification, and quantitation of peroxynitrite and its role in disease processes have concentrated much of our attention. Being a mediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens.

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Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions.

Ángel Catalá (2009)

Polyunsaturated fatty acids (PUFAs) and their metabolites have a variety of physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression. Lipids containing polyunsaturated fatty acids are susceptible to free radical-initiated oxidation and can participate in chain reactions that increase damage to biomolecules. Lipid peroxidation, which leads to lipid hydroperoxide formation often, occurs in response to oxidative stress. Hydroperoxides are usually reduced to their corresponding alcohols by glutathione peroxidases. However, these enzymes are decreased in certain diseases resulting in a temporary increase of lipid hydroperoxides that favors their degradation into several compounds, including hydroxy-alkenals. The best known of these are: 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE), which derive from lipid peroxidation of n-6 and n-3 fatty acids, respectively. Compared to free radicals, these aldehydes are relatively stable and can diffuse within or even escape from the cell and attack targets far from the site of the original event. These aldehydes exhibit great reactivity with biomolecules, such as proteins, DNA, and phospholipids, generating a variety of intra and intermolecular covalent adducts. At the membrane level, proteins and amino lipids can be covalently modified by lipid peroxidation products (hydoxy-alkenals). These aldehydes can also act as bioactive molecules in physiological and/or pathological conditions. In addition this review is intended to provide an appropriate synopsis of identified effects of hydroxy-alkenals and oxidized phospholipids on cell signaling, from their intracellular production, to their action as intracellular messenger, up to their influence on transcription factors and gene expression.

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Author and article information

Contributors

Giancarlo Aldini

Journal

Journal ID (nlm-ta): Redox Biol

Journal ID (iso-abbrev): Redox Biol

Title: Redox Biology

Publisher: Elsevier

ISSN (Electronic): 2213-2317

Publication date PMC-release: 17 February 2021

Publication date Collection: June 2021

Publication date (Electronic): 17 February 2021

Volume: 42

Electronic Location Identifier: 101899

Affiliations

[a ]Department of Pharmaceutical Sciences (DISFARM), Università Degli Studi di Milano, Via Mangiagalli 25, 20133, Milan, Italy

[b ]Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138, Milan, Italy

Author notes

[∗ ]Corresponding author. giancarlo.aldini@ 123456unimi.it

Article

Publisher Item ID: S2213-2317(21)00047-1 Publisher ID: 101899

DOI: 10.1016/j.redox.2021.101899

PMC ID: 8113032

PubMed ID: 33642248

SO-VID: aad9402e-5ec0-40ee-8556-006efa8c1c6e

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 4 January 2021

Date revision received : 1 February 2021

Date accepted : 12 February 2021

Categories

Subject: Articles from the Special Issue on Oxidative stress in retina and retinal pigment epithelium in health and disease; Edited by Dr. Vera Bonilha

Keywords: lipid peroxidation,reactive carbonyl species,covalent adducts,protein carbonylation,analytical methods,biomarkers,acr, acrolein,adh, alcohol dehydrogenase,aldh, aldehyde dehydrogenases,apl, aminophospholipids,akr, aldo-keto reductase,dg, deoxyguanosine,dhn, 1,4-dihydroxy-2-nonene,dnph, dinitrophenylhydrazine,dr, deoxy-ribose,enos, endothelial nitric oxide synthase,esr, electron spin resonance,elisa, enzyme-linked immunosorbent assay,f2-isops, f2-isoprostanes,gc-ms, gas chromatography coupled to mass spectrometry,gs-hna, 3-(s-glutathio-nyl)-4-hydroxynonanoic acid,gsh-dhn, 3-(s-glutathionyl)-1,4-dihydroxynonane,go, glyoxal,hplc, high-performance liquid chromatography,isolg, isolevuglandins,isok, isoketals,hplc-ms, high-performance liquid chromatography coupled to mass spectrometry,3-pma, 3-hydroxypropyl mercapturic acid,hna, carboxyl 4-hydroxy-2-nonenoic acid,hne, 4-hydroxy-nonenal,hhe, 4-hydroxy-hexenal,lloq, lower limit of quantification,lpo, lipid peroxidation,ma, mercapturic acid,mrm, multiple reaction monitoring,ms, mass spectrometry,mda, malondialdehyde,mgo, methylglyoxal,nrf2, nuclear factor erythroid 2–related factor 2,one, 4-oxo-nonenal,pe, phosphatidylethanolamine,ps, phosphatidylserine,pufa, poly unsaturated fatty acids,rcs, reactive carbonyl species,rcs-pa, rcs-protein adducts,ros, reactive oxygen species,rns, reactive nitrogen species,tbars, thiobarbituric acid-reactive substances,uloq, upper limit of quantification

Data availability:

Keywords: lipid peroxidation, reactive carbonyl species, covalent adducts, protein carbonylation, analytical methods, biomarkers, acr, acrolein, adh, alcohol dehydrogenase, aldh, aldehyde dehydrogenases, apl, aminophospholipids, akr, aldo-keto reductase, dg, deoxyguanosine, dhn, 1,4-dihydroxy-2-nonene, dnph, dinitrophenylhydrazine, dr, deoxy-ribose, enos, endothelial nitric oxide synthase, esr, electron spin resonance, elisa, enzyme-linked immunosorbent assay, f2-isops, f2-isoprostanes, gc-ms, gas chromatography coupled to mass spectrometry, gs-hna, 3-(s-glutathio-nyl)-4-hydroxynonanoic acid, gsh-dhn, 3-(s-glutathionyl)-1,4-dihydroxynonane, go, glyoxal, hplc, high-performance liquid chromatography, isolg, isolevuglandins, isok, isoketals, hplc-ms, high-performance liquid chromatography coupled to mass spectrometry, 3-pma, 3-hydroxypropyl mercapturic acid, hna, carboxyl 4-hydroxy-2-nonenoic acid, hne, 4-hydroxy-nonenal, hhe, 4-hydroxy-hexenal, lloq, lower limit of quantification, lpo, lipid peroxidation, ma, mercapturic acid, mrm, multiple reaction monitoring, ms, mass spectrometry, mda, malondialdehyde, mgo, methylglyoxal, nrf2, nuclear factor erythroid 2–related factor 2, one, 4-oxo-nonenal, pe, phosphatidylethanolamine, ps, phosphatidylserine, pufa, poly unsaturated fatty acids, rcs, reactive carbonyl species, rcs-pa, rcs-protein adducts, ros, reactive oxygen species, rns, reactive nitrogen species, tbars, thiobarbituric acid-reactive substances, uloq, upper limit of quantification

Lipid peroxidation derived reactive carbonyl species in free and conjugated forms as an index of lipid peroxidation: limits and perspectives

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Abstract

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Journal of Circulating Biomarkers

Most cited references 117

Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges.

Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine

Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions.

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Article

History

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