The role of nitro-reduction and nitric oxide in the toxicity of chloramphenicol.
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. 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. 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. These observations suggest that involvement of the para-nitro group of chloramphenicol could cause both hemotoxicity and hypotension in susceptible individuals.
Holt
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Karim Centre for Meningitis Research, ICSM Department of Paediatrics & Neonatal Medicine, Queen Charlotte's & Chelsea Hospital, London, UK.
Bajoria
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D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000983:Antipyrine / Q000032:analysis; D001808:Blood Vessels / Q000187:drug effects*; D002701:Chloramphenicol / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion / Q000379:methods; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy
D000900:Anti-Bacterial Agents; D009569:Nitric Oxide; D002701:Chloramphenicol; D000983:Antipyrine