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Free radical-mediated reactions have been well known in chemistry and physical chemistry for many years. Applying this knowledge to living organisms, biochemists have shown that reactive free radicals are formed at many intracellular sites during normal metabolism, and they have started to suggest possible roles in various pathological processes and conditions, for example in radiation damage, in the metabolism of xenobiotics, in carcinogenesis and in metabolic disorders. At present, a large and relevant mass of experimental evidence supports the view that reactive free radicals are involved in the pathogenesis of several diseases and syndromes. This literature has captured the attention and interest of people involved in the biomedical field. Exciting developments in radical research are probable in the near future, establishing a greater interaction between basic science research and medicine. While the task of defining the involvement of free radicals in human pathology is difficult, it is nonetheless extremely important that such interaction be fulfilled as soon as possible. These were the considerations motivating us during the organization of the VI Biennial Meeting of the International Society for Free Radical Research held in Torino, Italy, in June 1992, and also during the preparation of this book. Experts in the various aspects of free radical research were invited to participate in the Torino Meeting and to contribute chapters for this volume.
Sommario
Free radicals: Generation and mechanisms of damage.- Trevor Slater, free radical redox chemistry and antioxidants: from NAD+ and vitamin C to CCl4 and vitamin E, to thiols, myoglobin and vitamins A and D.- Regulation of gene expression in adaptation to oxidative stress.- Radiation-induced free radical reactions.- Nitric oxide and related radicals.- Mechanisms of oxidative cell damage.- Lipid peroxidation. An overview.- Lipid peroxidation in dividing cells.- Formation and metabolism of the lipid peroxidation product 4-hydroxynonenal in liver and small intestine.- DNA damage by reactive oxygen species. The role of metals.- Inflammation and a mechanism of hydrogen peroxide cytotoxicity.- Aging.- Free radical theory of aging.- Oxidative stress state in aging and longevity mechanisms.- Maillard reaction and oxidative stress are interrelated stochastic mechanisms of aging.- The glycoxidation: a non enzymatic mechanism of protein aging.- Marker or mechanism: possible pro-oxidant reactions of radical-damaged proteins in aging and atherosclerosis, an age-related disease.- Cancer.- Carcinogenesis and free radicals.- Derangements of cellular metabolism in the pre-malignant syndrome.- Molecular mechanisms of oxidant carcinogenesis.- Involvement of oxy-radicals in cancer cell killing and growth.- Free radicals and active states of oxygen in human cancer due to environmental pollutants: public health optimism and scientific skepticism.- Metabolic disorders.- Hepatotoxicity of experimental hemochromatosis.- Role of inducible cytochrome P450 in the liver toxicity of poly-halogenated aromatic compounds.- CBrCl3 toxicity in isolated rat hepatocytes: survey on reasonable cytotoxic mechanisms.- Evidence for a possible role of lipid peroxidation in experimental liver fibrosis.- Ethanol-inducible cytochrome P450 2E1. regulation, radical formation and toxicological importance.- Free radical-induced impairment of liver glycosylation processes in ethanol intoxication.- Oxidative damage and human alcoholic disease. Experimental and clinical evidence.- Oxidised low density lipoproteins.- Protein peroxides: formation by superoxide-generating systems and during oxidation of low density lipoprotein.- An in vitro approach to the study of inflammatory reactions in atherosclerosis.- Antioxidants.- Antioxidant defenses in eukaryotic cells: an overview.- Electron paramagnetic resonance studies on flavonoid compounds.- Antioxidant mechanisms of vitamin E and beta-carotene.- A nuclear pool of glutathione in hepatocytes.- Phospholipid hydroperoxide glutathione peroxidase is the major selenoperoxidase in nuclei and mitochondria of rat testis.- Medical applications of antioxidants: an update of current problems.- Free radicals and antioxidants in muscular and neurological diseases and disorders.- Pharmaceutical intervention for the prevention of post-ischemic reperfusion injury.- Metal-catalyzed free radical injuries in chilhood: disorders and pharmaceutical intervention.- Effect of antioxidants on oxidative modification of human low density lipoproteins.- Approaches to the therapy of glutathione deficiency.- Utilization of oral glutathione.- Author Index.
