The role of nitro-reduction and nitric oxide in the toxicity of chloramphenicol

Abstract

1 Recent work on the toxicology of chloramphenicol suggests that its propensity to cause damage to the blood forming organs may be related to its potential for nitro-reduction and the subsequent production of nitric oxide. 2 In this study both aerobic and anaerobic nitro-reduction of chloramphenicol by human foetal and neonatal liver results in the production of the amine derivative. However intermediates of the reaction nitroso-or glutathionesulphinamido-chloramphenicol could not be detected by hplc. 3 Perfusion of chloramphenicol through isolated lobules of human placentae caused a decrease in blood pressure at a time which coincided with a peak of nitric oxide production. However, although the pressure drop could be reversed by an inhibitor of nitric oxide synthetase, the nitric oxide profile remained the same. 4 These observations suggest that involvement of the para-nitro group of chloramphenicol could cause both hemotoxicity and hypotension in susceptible individuals.