Abstract
The mechanism of toxicity of redox active compounds such as quinones, bipyridylherbicides and nitrocompounds varies with the compound1. Common to these types of redox active compounds is that they may be enzymatically reduced by one electron reduction catalyzed by the microsomal enzymes NADPH, cyt-P450 reductase and NADH cyt-b5 reductase and the mitochondrial NADH ubiquinone oxidoreductase. The free radical intermediates formed may be reactive by themselves or, depending on their one electron redox potentials, react with molecular oxygen with the resulting formation of superoxide anion radical (\( {O_2}\overline \bullet \)). This process is termed redox cycling. The so formed (\( {O_2}\overline \bullet \)) readily dismutates either enzymatically or nonenzymatically to hydrogen peroxide (H2O2) which in turn, if not metabolized, undergoes heterolytic cleavage in a Fenton-type reaction with the formation of the very reactive hydroxyl radical (·OH). In addition to redox cycling some redox active compounds may react directly with cellular constituents. They may for instance oxidize both pyridine nucleotides and soluble and protein-bound thiols, as well as arylate and alkylate protein and DNA. Many quinones have for instance been shown to readily react with GSH to form GSH-quinone conjugates and with protein thiols to form alkylated proteins2–4.
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Atzori, L., Cotgreave, I.A., Moldéus, P. (1990). Critical Events in the Toxicity of Redox Active Drugs. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_21
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DOI: https://doi.org/10.1007/978-1-4615-3768-7_21
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