Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.

Publisher Summary This chapter describes the malondialdehyde (MDA) as index of lipid peroxidation. The determination of malondialdehyde (MDA) has attracted widespread interest, because it appears to offer a facile means of assessing lipid peroxidation in biological materials. Malondialdehyde occurs in biological materials in free state and in various covalently bound forms. Urine also contains small amounts of MDA adducts with guanine, the phospholipid bases serine and ethanolamine, and other unidentified reactants. Free MDA is a minor and variable excretory product. It is apparent from the occurrence of these derivatives in urine that MDA forms adducts with proteins, nucleic acids, and other substances in vivo, and this compromises the assessment of lipid peroxidation in the tissues based on the determination of free MDA. The pH required for maximum yield of MDA varies among biological materials depending on the nature of the derivatives present. MDA may be generated during hydrolysis by the oxidation of polyunsaturated fatty acids (PUFA) in the sample and by the degradation of preexisting oxidation products. Pigments present in the sample, or generated during hydrolysis, also can interfere in the colorimetric assessment of MDA. These problems, and possibilities for their resolution, are discussed in the chapter.

Malondialdehyde determination as index of lipid peroxidation

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

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

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Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

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

Although malondialdehyde (MDA) is extensively metabolized to CO2, small amounts are nevertheless excreted in an acid-hydrolyzable form in rat urine. In this study, urinary MDA was evaluated as an indicator of lipid peroxidation in the diet and in the tissues. MDA was released from its bound form(s) in urine by acid treatment and determined as the TBA-MA derivative by HPLC. MDA excretion by the rat was found to be responsive to oral administration of the Na enol salt and to peroxidation of dietary lipids. Urinary MDA also increased in response to the increased lipid peroxidation in vivo produced by vitamin E deficiency and by administration of iron nitrilotriacetate. Chronic feeding of a diet containing cod liver oil led to increases in MDA excretion which were not completely eliminated by fasting or feeding a peroxide-free diet, indicating that there was increased lipid peroxidation in vivo. MDA excretion was not responsive to Se deficiency or CCl4 administration. DPPD, a biologically active antioxidant, but not BHA, a non-biologically active antioxidant, prevented the increase in MDA excretion in vitamin E deficient animals. The results indicate that MDA excretion can serve as an indicator of the extent of lipid peroxidation in the diet and, under conditions which preclude a dietary effect, as an index of lipid peroxidation in vivo.

Urinary malondialdehyde as an indicator of lipid peroxidation in the diet and in the tissues

Interest in malondialdehyde (MDA) metabolism stems from its formation as a product of lipid peroxidation in the diet and in the tissues; its reactivity with functional groups of nucleic acid bases, proteins and phospholipids; its mutagenicity in bacteria, and its reported skin and liver carcinogenicity in animals. Administration of the Na enol salt of MDA in the drinking water of mice over a range of 0.1-10.0 micrograms/g/day for 12 mo produced dose-dependent hyperplastic and neoplastic changes in liver nuclei and increased mortality at the highest level but produced no gross hepatic tumors. Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%. [1,3-14C]MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine. Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis. Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA. N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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L. G. Mcgirr

Papers

Urinary malondialdehyde as an indicator of lipid peroxidation in the diet and in the tissues

The metabolism of malondialdehyde

Identification of N alpha-acetyl-epsilon-(2-propenal)lysine as a urinary metabolite of malondialdehyde.