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

Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Role of free radicals and catalytic metal ions in human disease: an overview.

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

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.

https://link.springer.com/content/pdf/10.1097%2FWOX.0b013e3182439613.pdf

Oxidative Stress and Antioxidant Defense

A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials

Human and bovine milk were analyzed for vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 25,26-dihydroxyvitamin D and 1,25-dihydroxyvitamin D using exhaustive chromatographic purification procedures coupled with ligand binding assays. Human milk contained the following amounts of antirachitic sterols (pg/ml, mean +/- SD, n = 5): 39 +/- 9 vitamin D; 311 +/- 31 25-hydroxyvitamin D; 52 +/- 8 24,25-hydroxyvitamin D; 32 +/- 9 25,26-dihydroxyvitamin D; 5.1 +/- 0.3 1,25-dihydroxyvitamin D. Normal bovine milk contained levels of these sterols comparable to those found in human milk. Increasing the oral dose of vitamin D to the cows was reflected by an increase of the parent vitamin and 25-hydroxyvitamin D in the milk. Vitamin D-binding protein concentration in human milk whey, determined by Ouchterlony immunodiffusion and radioimmunoassay, was 1--2% of the levels observed in the plasma and was dependent on the stage of lactation. Vitamin D and its metabolites were shown initially to be present in the whey portion but with time migrated into the fat portion of milk. The antirachitic sterols detected account for approximately 25 IU/liter and 27 IU/liter of antirachitic activity in human and bovine milk, respectively. In both species 25-hydroxyvitamin D comprised the majority of the antirachitic sterols detected in normal milk.

Vitamin D and Its Metabolites in Human and Bovine Milk

Determination of malonaldehyde in biological materials by high-pressure liquid chromatography

The metabolism of malonaldehyde (MA) was investigated in vivo using male Wistar rats and in vitro using rat liver mitochondria. Twelve hr after intubation with [1,3-14C] MA, 60–70%, 5–15% and 9–17% of administered radioactivity was recovered in expired CO2, feces and urine, respectively. In rats intubated with [1,2-14C] acetate, the corresponding values were 68–82%, 1–2% and 2–3%.14CO2 evolution was initially slower after14C-MA administration than after14C-acetate administration and more radioactivity was excreted in the feces and urine. In vitro experiments using [1,3-14C] MA showed that MA is metabolized primarily in the mitochondria via reactions involving O2 utilization and14CO2 production. The apparent Km and Vmax were 0.5 mM and 9.3 nmol/min/mg protein for O2 uptake, respectively, and 2.0 mM and 2.4 nmol/min/mg protein for14CO2 production. Addition of malonic acid to mitochondrial incubates at concentrations inhibitory to succinate dehydrogenase did not affect MA-induced O2 uptake but enhanced14CO2 production from14C-MA.14C-Acetate appeared to be the major accumulating metabolite in rat liver mitochondrial preparations following a 120-min incubation with14C-MA. A probable biochemical route for MA metabolism involves oxidation of MA by mitochondrial aldehyde dehydrogenase followed by decarboxylation to produce CO2 and acetate.

Metabolism of malonaldehyde in vivo and in vitro

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.

H. H. Draper

Papers

A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials

Vitamin D and Its Metabolites in Human and Bovine Milk

Determination of malonaldehyde in biological materials by high-pressure liquid chromatography

Metabolism of malonaldehyde in vivo and in vitro

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