Antioxidants chronic toxicity

A number of antioxidants have been accepted by the FDA as indirect additives for polymers used in food appHcations. Acceptance is deterrnined by subchronic or chronic toxicity in more than one animal species and by the concentration expected in the diet, based on the amount of the additive extracted from the polymer by typical foods or solvents that simulate food in their extractive effects. Only materials of insignificant risk to the consumer are regulated by the FDA for use in plastics contacted by food stuffs. 

Variations in the use pattern of industrial and agricultural chemicals throughout the world preclude standardization by international organizations such as OECD. Despite this fact, common dietary constituents, which are known to influence toxicity are antioxidants, unsaturated fatty acids, and selenium. These must be present in interfering concentrations. The potential impact of several common dietary contaminants on chronic toxicity assessment therefore, necessitates that special attention be given to their presence. In this respect, substances of concern include pesticide residues, chlorinated and polycyclic aromatic hydrocarbons, estrogens, heavy metals, nitrosamines, and mycotoxins. 

Firstly, I will discuss recent evidence supporting the hypothesis that free radicals contribute to important chronic diseases in man and exert an important life-shortening effect. Secondly, I will review data on the toxicity of lipid hydroperoxides and their decomposition products, since lipid hydroperoxides can be a source of free radicals in vivo. And lastly, I will review a system under study in our laboratory in which quantitative data on lipid peroxidation and antioxidants is being obtained using linoleic acid in SDS micelles. 

Indications Improves lipid metabolism, red blood cell count, and antioxidant status, chronic fatigue syndrome, dementia, angina, post-MI cardioprotection, congestive heart failure, valproate toxicity, anorexia Category Food supplement Half-life N/A... 

A-Acetylcysteine is administered in the ace-toaminophen toxicity. It replenishes the hepatic stores of glutathione (Chapter 17). A-Acetylcysteine is also used in the treatment of pulmonary diseases including cystic fibrosis (Chapter 12). In patients with chronic renal insufficiency, prophylactic oral administration of A-Acetylcysteine have been used in the prevention of further renal impairment due to administration of radiographic contrast agents. In this setting presumably A-Acetylcysteine functions as an antioxidant and augments the vasodilatory effect of nitric oxide via the formation of S-nitrosothiol (Chapter 17). 

The trend to go for potent, naturally derived antioxidant molecules over those of synthetic origin is ever increasing. To this class belong chitosan and several of its derivatives, which being safe and non-toxic offer protection from free radicals, thus retarding the progress of numerous chronic diseases [139]. It is known that the antioxidant effect of chitosan varies with its molecular weight and viscosity, as shown in cooked comminuted fish flesh model systems [140]. 

As an effective bona fide antioxidant in both plasma and intracellular membrane, Pycnogenol can significantly contribute to the maintenance of cellular redox homeostasis, in particular in the course of events that are likely to overwhelm the capacity to cope with an increased production of RONS, such as in chronic inflammations, thereby reducing Ae possibility of cellular damage at different targets. The ability of Pycnogenol to act as a lipid peroxidation chain breaker is also likely to reduce the toxic consequences of a free-radical-induced cellular stress. 

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