Bioactivation and bound residues

Food Additives and Contaminants
V Burgat-SacazeP Delatour

Abstract

Most toxic chemicals undergo bioactivation before they can exert their noxious effects. These biotransformations produce very reactive intermediate metabolites which covalently bind to vital cellular components and can lead to a specific toxicity. Several categories of reactive metabolites can be postulated: (1) electrophilic compounds, (2) free radicals, (3) compounds able to form activated species of oxygen (oxidative stress). Only the two first groups covalently bind to cellular components; these adducts are a part of the bound residues of veterinary drugs. Electrophilic metabolites react with nucleophilic centres of various molecules (proteins, nucleic acids, amino-acids . . .). These active intermediates (oxiranes, quinoneimines, carbo cations . . .) appear during oxidation reactions specifically catalysed by the microsomal mixed-function oxidase. Hepatic necrosis induced by Acetaminophen can be a model and will be discussed. Free radicals are also produced by microsomal metabolism. They bind covalently to cellular lipids and proteins and induce a lipidic peroxidation. Carbon tetrachloride-induced hepatic injury is an example. These concepts dealing with bioactivation, the nature of the covalents' adducts and their toxicol...Continue Reading

Citations

Jul 3, 2007·Journal of Agricultural and Food Chemistry·Silvio UhligDirk Petersen

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