The myelotoxicity of chloramphenicol: in vitro and in vivo studies: I. In vitro effects on cells in culture.
1 Chloramphenicol is used extensively in non-industrialized countries for the treatment of life-threatening infections because it is cheap and effective, despite its known hemotoxicity and linkage to fatal aplastic anaemia. It is important to define the mechanism of toxicity so that means can be devised to ameliorate the toxic effects in order to produce safer usage. 2 Chloramphenicol, at concentrations from 5 mM to 2 mM initiated apoptosis in dividing cells from a monkey kidney-derived cell line and in haematopoietic progenitor cells from human neonatal cord blood. 3 Growth of progenitor cells was suppressed at concentrations of chloramphenicol which would be considered less than therapeutic during patient treatment. 4 These effects could be ameliorated in progenitor cells by co-culture with the antioxidant mercaptoethylamine and in monkey kidney cells by co-culture with vitamin C. 5 This is the first report of apoptosis in chloramphenicol toxicity and suggests a possible link between a metabolic event i.e. the production of free radicals; a morphological effect, apoptosis; and a clinical effect, bone marrow suppression and aplastic anaemia.
Holt
D E
DE
Karin Centre for Meningitis Research, Queen Charlotte's & Chelsea Hospital, London, UK.
Ryder
T A
TA
Fairbairn
A
A
Hurley
R
R
Harvey
D
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000633:toxicity*; D002522:Chlorocebus aethiops; D003543:Cysteamine / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D014709:Vero Cells / Q000166:cytology / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D003543:Cysteamine; D002701:Chloramphenicol