Review
Lipid peroxidation cannot be used as a universal criterion of oxidative stress

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Abstract

Oxidative stress is a term used to denote the imbalance between the concentrations of reactive oxygen and nitrogen species and the defense mechanisms of the body. Although it is generally accepted that such an imbalance plays a pivotal role in many pathologies, the term “oxidative stress” remains ill defined. In an attempt to evaluate the relationship between various assays of oxidative stress, we have analyzed the correlations between the results reported in those publications in which “oxidative stress” has been assayed by at least two methods. We found good correlations between the concentrations of several peroxidation products, including malondialdehyde, F2-Isoprostanes, lipid hydroperoxides, conjugated dienes, glutathione and protein carbonyls, but not with other criteria of “individual oxidative status” such as the concentration of antioxidants and products of DNA fragmentation (the “comet” assay). In light of these findings, we divide the assays used for evaluation of “oxidative stress” into the following three categories: (i) assays based on measuring the concentrations of oxidation products of lipids, proteins and DNA, as well as the concentrations of antioxidants, (ii) assays used to evaluate the oxidative and reductive capacity of biological fluids and (iii) assays used to evaluate the ex vivo susceptibility of lipids to oxidation upon their exposure to a source of free radicals. Our analyses demonstrate that oxidative stress cannot be defined in universal terms.

Two results are of special interest:

  • 1.

    the commonly used criteria based on lipid peroxidation can not be regarded as a general estimate of the individual “oxidative status”.

  • 2.

    the levels of antioxidants exhibit a non-monotonic relation with other criteria for oxidative stress.

Further research is required to evaluate the significance of the latter finding.

Introduction

Oxidative stress is a term commonly used to denote the imbalance between the concentrations of reactive oxygen and nitrogen species (ROS and RNS, respectively) and the antioxidative defense mechanisms of the body. Such an imbalance plays a pivotal role in many pathologies [1], [2]. Yet, the term “oxidative stress” is not well defined. More than 40 indices2 are in common use to assess “oxidative stress”[3], [4], implementing more than a hundred methods.3

The prevailing paradigm is that the “oxidative status” of a person can be evaluated from the composition of his body fluids and tissues with respect to oxidation products, promoters and/or inhibitors of peroxidation. Alternatively, the “oxidative status” can be assessed either on the basis of the overall oxidative/reductive potency of a given specimen (e.g. blood or urine) or on the basis of the susceptibility of the various oxidizable components of body fluids to ex vivo peroxidation.

The most commonly used criteria of oxidative stress are those based either on determination of the concentrations of lipid oxidation products in body fluids or on the susceptibility of lipids to peroxidation induced ex vivo either by transition metal ions or by generators of free radicals.

In general, the criteria used to assess oxidative stress can be categorized as in Scheme 1A. Each of these criteria can be evaluated in terms of various indices, using various methods, as summarized in Scheme 1B [3], [4], [5]. The various specimens tested for evaluation of the “oxidative status” are given in Scheme 2.

In the present mini-review we describe the various indices and methods used for assessing the oxidative stress and the correlations between the results obtained through the use of these methods and specimens. These correlations (and the lack thereof) demonstrate that oxidative stress cannot be defined in universal terms. Hence, lipid peroxidation by itself can not be used to evaluate the individual “oxidative status”.

Section snippets

Assessing oxidative stress, indices and methods

The methods available for evaluation of oxidative stress may be divided into three main categories (as shown in Scheme 1A). These methods assess the following indices:

  • Indices based on the composition of various biological specimens with respect to the concentrations of various relevant components.

  • Indices based on the oxidative or reductive potency of a biological fluid.

  • Indices based on the susceptibility of various components of body fluids or their components to ex-vivo oxidation

Meta-analysis of published results

Our main objective in this study was to establish the interrelationships between the results obtained by the different methods and indices that are used for assessing oxidative stress. For this purpose we reviewed 50 studies published in English [7], [12], [13], [24], [26], [38], [49], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87],

Concluding remarks

In many respects, the most direct way of assessing oxidative stress is by measuring the level of free radicals. Unfortunately, the available data based on such assays is very limited and insufficient for comparison with the less direct but commonly used methods. None of these methods can be defined as the most appropriate criterion for defining “oxidative stress” in universal terms. Which method is of relevance to a given research depends on the research objective. Assessment of the “oxidative

Acknowledgements

We would like to thank Dr Edit Schnitzer, Sigal Gal, Dorit Samocha-Bonet, and Dalia Artal, for their great help in editing this paper. The Israeli Academy of science and humanities is acknowledged for financial support.

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    Y. Dotan is an DMD-PhD student in Sackler Faculty of Medicine. This work constitutes a part of his PhD thesis, to be submitted to the senate of Tel Aviv University.

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