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.

Metal contamination issues are becoming increasingly common in India and elsewhere, with many documented cases of metal toxicity in mining industries, foundries, smelters, coal-burning power plants and agriculture. Heavy metals, such as cadmium, copper, lead, chromium and mercury are major environmental pollutants, particularly in areas with high anthropogenic pressure. Heavy metal accumulation in soils is of concern in agricultural production due to the adverse effects on food safety and marketability, crop growth due to phytotoxicity, and environmental health of soil organisms. The influence of plants and their metabolic activities affects the geological and biological redistribution of heavy metals through pollution of the air, water and soil. This article details the range of heavy metals, their occurrence and toxicity for plants. Metal toxicity has high impact and relevance to plants and consequently it affects the ecosystem, where the plants form an integral component. Plants growing in metal-polluted sites exhibit altered metabolism, growth reduction, lower biomass production and metal accumulation. Various physiological and biochemical processes in plants are affected by metals. The contemporary investigations into toxicity and tolerance in metal-stressed plants are prompted by the growing metal pollution in the environment. A few metals, including copper, manganese, cobalt, zinc and chromium are, however, essential to plant metabolism in trace amounts. It is only when metals are present in bioavailable forms and at excessive levels, they have the potential to become toxic to plants. This review focuses mainly on zinc, cadmium, copper, mercury, chromium, lead, arsenic, cobalt, nickel, manganese and iron.

Heavy metals, occurrence and toxicity for plants: a review

The ferritins: molecular properties, iron storage function and cellular regulation☆

The use of dichlorofluorescin (DCFH) as a measure of reactive oxygen species was studied in aqueous media. Hydrogen peroxide oxidized DCFH to fluorescent dichlorofluorescein (DCF), and the oxidation was amplified by the addition of ferrous iron. Hydrogen peroxide-induced DCF formation in the presence of ferrous iron was completely inhibited by deferoxamine and partially inhibited by ethylenediaminetetraacetic acid, but was augmented by diethylenetriaminepentaacetic acid. Iron-peroxide-induced oxidation of DCFH was partially inhibited by catalase but not by horseradish peroxidase. Nonchelated iron-peroxide oxidation of DCFH was partially inhibited by several hydroxyl radical scavengers, but was independent of the scavenger concentration, and this suggests that free hydroxyl radical is not involved in the oxidation of DCFH in this system. Superoxide anion did not directly oxidize DCFH. Data suggest that H2O2-Fe(2+)-derived oxidant is mainly responsible for the nonenzymatic oxidation of DCFH. In addition, peroxidase alone and oxidants formed during the reduction of H2O2 by peroxidase oxidize DCFH. Since DCFH oxidation may be derived from several reactive intermediates, interpretation of specific reactive oxygen species involved in biological systems should be approached with caution. However, DCFH remains an attractive probe as an overall index of oxidative stress in toxicological phenomena.

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Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress.

The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochrome c reductase activities were significantly reduced, whereas succinate cytochrome c reductase activity was normal. These results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that Parkinson's disease may be due to an environmental toxin with action(s) similar to those of MPTP.

Craig E. Thomas

Papers

Role of metals in oxygen radical reactions

Ferritin and superoxide-dependent lipid peroxidation.

Superoxide generation by NADPH-cytochrome P-450 reductase: the effect of iron chelators and the role of superoxide in microsomal lipid peroxidation.

Release of iron from ferritin by cardiotoxic anthracycline antibiotics

Rat liver microsomal NADPH-dependent release of iron from ferritin and lipid peroxidation