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Human & Experimental Toxicology
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The role of nitro-reduction and nitric oxide in the toxicity of chloramphenicol

Daphne E Holt

The Karim Centre for Meningitis Research, ICSM Department of Paediatrics & Neonatal Medicine, Queen Charlotte's & Chelsea Hospital, Goldhawk Road, London, W6 0XG, UK

Rekha Bajoria

Department of Obstetrics & Gynaecology, St Mary's Hospital, University of Manchester, Whitworth Park, Manchester, M13 0JH, UK

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.

Key Words: nitro-reduction • nitric oxide • chloramphenicol • apoptosis

Human & Experimental Toxicology, Vol. 18, No. 2, 111-118 (1999)
DOI: 10.1177/096032719901800208
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