Review
A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress

https://doi.org/10.1016/j.numecd.2005.05.003Get rights and content

Summary

Aim

Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. This aldehyde is a highly toxic molecule and should be considered as more than just a marker of lipid peroxidation. Its interaction with DNA and proteins has often been referred to as potentially mutagenic and atherogenic. This review is intended to briefly describe the physiological origin of MDA, to highlight its toxicity, describe and comment on the most recent methods of detection and discuss its occurrence and significance in pathology.

Data synthesis

In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed. The most recent and improved procedures for the evaluation of MDA in biological fluids are described and discussed. The evidence of the occurrence of increased MDA levels in pathology is described.

Conclusions

In the assessment of MDA, the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions. Moreover, no recent nutritional or medical trials report the use of one of the new and more reliable methods, some of which are undoubtedly accessible to virtually all the laboratories provided with a common HPLC or a spectrofluorimeter.

Introduction

Oxidative stress has been related to the etiopathogenesis of several chronic diseases and plays a paramount role in the aging process [1], [2]. Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. These products are mainly aldehydes, with the ability to exacerbate oxidative damage [3]. Longevity and high reactivity allow these molecules to act inside and outside the cells, interacting with biomolecules such as nucleic acids and proteins, often irreversibly damaging the delicate mechanisms involved in cell functionality.

Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. Since the 1960s several methods have been developed to assess this molecule in order to quantify the level of oxidative stress in vivo and in vitro. This review is intended to briefly describe its physiological origin, highlight its toxicity, describe and comment on the most recent methods of detection, and report its occurrence and significance in pathology.

Section snippets

In vivo origin of MDA

The main source of MDA in biological samples is the peroxidation of polyunsaturated fatty acids with two or more methylene-interrupted double bonds. Three attractive hypotheses describing the in vivo formation of MDA have been proposed. Pryor and Stanley [4], basing their hypothesised mechanism on the non-volatile nature of the MDA precursor, described that precursor as a bicyclic endoperoxide similar to the one formed during prostaglandin biosynthesis. The reaction describing the mechanism of

Reactivity and toxicity of MDA

In its physiological state, at neutral pH, MDA is present as an enolate anion and is of low chemical reactivity [6]. Nevertheless, this molecule is able to interact with nucleic acid bases to form several different adducts [8]. The main product of this reaction is known to be pyrimido-[1,2-α]purin-10(3H)-one deoxyribose, reported in the literature with many different abbreviations, such as M1dG, M1GdR or M1G (throughout this review M1G will be used), which is in equilibrium with the open form N2

Most recent methods of detection

Most assays to determine MDA have been developed on the basis of its derivatization with thiobarbituric acid (TBA). The condensation of these two molecules gives rise to a high absorbivity adduct which can be easily assessed with a spectrophotometer. Unfortunately, the specificity of the test based on this reaction is low, as TBA may react with several compounds other than MDA also derived from oxidation [14]. Moreover, the treatment of biological samples to obtain the condensation product is

Occurrence of MDA in pathology

In the last 20 years, MDA has been recognized as a relevant lipid peroxidation marker and as such, the measurement of MDA levels in biological samples from subjects affected by several diseases has been widely utilized. Accordingly, an increasing amount of literature has been published in the field. Therefore, this section should be interpreted as a brief extract of cases presented in the literature in which MDA has been found to be significantly modified in pathological contexts.

The involvement

Conclusion

What is the significance of determining and exactly quantifying MDA in human plasma? There are many answers. Efforts should be directed towards assessing MDA as a current and scientifically accepted marker of oxidative stress with worldwide recognition. Despite the many criticisms, its derivation from polyunsaturated fatty acids has been demonstrated and reported in this review. Nevertheless, in the assessment of MDA the most common methods of detection are insufficiently sensitive and

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