Detoxication of N-Oxygenated Arylamines in Erythrocytes. an Overview

Abstract

1. Reactive N-oxygenated arylamines, namely, N-hydroxyarylamines and nitroso-arenes, are toxic, mutagenic, carcinogenic and allergenic.

2. Erythrocytes are a very sensitive target for these compounds, but little is known of the detoxication capacity of these cells.

3. This overview considers the most important reactions of p-substituted N-oxygenated arylamines in red cells, namely, (i) ferrihaemoglobin formation by N-hydroxyarylamines with concomitant co-oxidation to nitrosoarenes; (ii) compartmentation of nitrosobenzenes by ligation to deoxyhaemoglobin, (iii) reactions of nitrosobenzene with glutathione, (iv) adduct formation of nitrosobenzenes with thiol groups of haemoglobin.

4. To predict the metabolic fate of N-oxygenated arylamines in red cells, the respective kinetic parameters of reactions (i) to (iv) have been determined, and indicate good linear free energy correlations (pH7.4, 37°C). These data may help to estimate the detoxication capacity of erythrocytes in vivo.