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Journal ArticleDOI

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

01 Jan 1991-Free Radical Biology and Medicine (Free Radic Biol Med)-Vol. 11, Iss: 1, pp 81-128
TL;DR: This review provides a comprehensive summary on the chemical properties of 4-hydroxyalkenals and malonaldehyde, the mechanisms of their formation and their occurrence in biological systems and methods for their determination, as well as the many types of biological activities described so far.
About: This article is published in Free Radical Biology and Medicine.The article was published on 1991-01-01. It has received 6456 citations till now. The article focuses on the topics: 4-Hydroxynonenal & Biotin hydrazide.
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Journal ArticleDOI
TL;DR: This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process and the role of enzymatic and non-enzymatic antioxidants in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors.

5,937 citations

Journal ArticleDOI
Paul Angulo1
TL;DR: Nonalcoholic fatty liver disease is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

4,705 citations

Journal ArticleDOI
TL;DR: This review focuses on biochemical concepts of lipidPeroxidation, 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 geneexpression and promoting cell death.
Abstract: 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.

3,647 citations


Cites background from "Chemistry and biochemistry of 4-hyd..."

  • ...4Hydroxynonenal (4-HNE), α, β-unsaturated electrophilic compounds, is the major type of 4-hydroxyalkenals endproduct, generated by decomposition of arachidonic acid and larger PUFAs, through enzymatic or nonenzymatic processes [49]....

    [...]

  • ...MDA production by enzymatic processes is well known but its biological functions and its possible dose-dependent dual role have not been studied although MDA is more chemically stable and membrane-permeable thanROS and less toxic than 4-HNE andmethylglyoxal (MG) [49]....

    [...]

  • ...MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs [49], through enzymatic or nonenzymatic processes (Figure 3)....

    [...]

  • ...The predominant n6 fatty acid is arachidonic acid (AA), which can be reduced (i) via enzymatic peroxidation to prostaglandins, leukotrienes, thromboxanes, and other cyclooxygenase, lipoxygenase or cytochrome P-450 derived products [4]; or (ii) via nonenzymatic peroxidation to MDA, 4-HNE, isoprostanes, and other lipid peroxidation end-products (more stables and toxic than hydroperoxides) through oxygen radical-dependent oxidative routes [49, 71]....

    [...]

  • ...When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases [49]....

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Journal ArticleDOI
TL;DR: The outcome of cirrhosis and liver-related death is not uniform across the spectrum of nonalcoholic fatty liver, and poor outcomes are more frequent in patients in whom biopsies show ballooning degeneration and Mallory hyaline or fibrosis.

3,167 citations

References
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Book ChapterDOI
TL;DR: This chapter describes the malondialdehyde (MDA) as index of lipid peroxidation, a determination that appears to offer a facile means of assessing lipidperoxidation in biological materials.
Abstract: 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.

3,731 citations

Book ChapterDOI
TL;DR: This chapter discusses the methods used for the qualitative and quantitative determination of aldehydes in biological systems and focuses on 4-hydroxynonenal and malondialdehyde, which are in many instances the most abundant individual aldehyde resulting from lipid peroxidation.
Abstract: Publisher Summary This chapter discusses the methods used for the qualitative and quantitative determination of aldehydes in biological systems. It focuses on 4-hydroxynonenal (HNE) and malondialdehyde (MDA). 4-Hydroxynonenal is produced as a major product of the peroxidative decomposition of polyunsaturated fatty acids (PUFA) and possesses cytotoxic, hepatotoxic, mutagenic, and genoroxic properties. Increased levels of HNE are found in plasma and various organs under conditions of oxidative stress. In addition to HNE, lipid peroxidation generates many other aldehydes that may also be of toxicological significance. Malondialdehyde is in many instances the most abundant individual aldehyde resulting from lipid peroxidation, and its determination by thiobarbituric acid (TBA) is one of the most common assays in lipid peroxidation studies. In vitro MDA can alter proteins, DNA, RNA, and many other biomolecules. Recently, it has been demonstrated with monoclonal antibodies that malonaldehyde-altered protein occurs in atheroma of hyperlipidemic rabbits.

3,113 citations

Journal ArticleDOI
25 Jan 1985-Science
TL;DR: Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents.
Abstract: There is convincing evidence that cellular prooxidant states--that is, increased concentrations of active oxygen and organic peroxides and radicals--can promote initiated cells to neoplastic growth. Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents. Many of these agents are promoters or complete carcinogens. They cause chromosomal damage by indirect action, but the role of this damage in carcinogenesis remains unclear. Prooxidant states can be prevented or suppressed by the enzymes of the cellular antioxidant defense and low molecular weight scavenger molecules, and many antioxidants are antipromoters and anticarcinogens. Finally, prooxidant states may modulate the expression of a family of prooxidant genes, which are related to cell growth and differentiation, by inducing alterations in DNA structure or by epigenetic mechanisms, for example, by polyadenosine diphosphate-ribosylation of chromosomal proteins.

2,488 citations