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

Free radicals, metals and antioxidants in oxidative stress-induced cancer

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.

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.

Nonalcoholic fatty liver disease.

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.

/pdf/lipid-peroxidation-production-metabolism-and-signaling-234bwmyps5.pdf

Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

While many pathobiochemical consequences of lipid peroxidation like hepatotoxicity, ageing and artherosclerosis have been described in the literature, no non-destructive biochemical function of lipid peroxidation has been demonstrated unequivocally. A negative association between the extent of lipid peroxidation in tumour cells and their proliferative behaviour has been postulated (Bartoli and Galeotti 1979). Experimental evidence is available in the literature for the following factors, which may contribute to this negative association: (a) Decreased content of polyunsaturated fatty acids, (b) Shift of the balance between pro-oxidant (e. g. iron) and antioxidant (e. g. glutathione) substances to the antioxidant side. (c) decreased activity of peroxidative enzymes (e. g. NADPH-cytochrome c reductase), (d) reduced access of oxygen as a consequence of increased tumour membrane rigidity.

Iron-Induced Lipid Peroxidation and Inhibition of Proliferation in Animal Tumour Cells

A new PMN migration test was introduced in traumatology to measure the acute, inflammatory response after surgery in a patient with uncomplicated wound healing and in a case of acute, early postoperative infection. Polymorphonuclear neutrophil granulocyte (PMN) - behaviour was studied by quantifying the neutrophil migration activity (NMA), which combines PMN-stimulation and PMN-distribution in a migration filter device simulating "in vivo"-conditions. While in uncomplicated wound healing the NMA was within the normal range, in an acute, early infection migratory stimulation reached a maximum on the 5th postsurgical day followed by a decrease during the following days. This decrease is probably an expression of an increased PMN-turnover and excessive phagocytosis. PMN-behaviour changing from migration to phagocytosis is regarded as an indicator of wound healing complications before clinical symptoms occur.

R. J. Schaur

Papers

Iron-Induced Lipid Peroxidation and Inhibition of Proliferation in Animal Tumour Cells

Neutrophil Migration Activity (NMA) - A new migration test for the monitoring of wound healing in traumatology?