Chloramphenicol-induced bone marrow injury: Possible role of bacterial metabolites of chloramphenicol

Joaquin J Jimenez, G. K. Arimura, W. H. Abou-Khalil, M. Isildar, Adel A Yunis

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Abstract

To explore the potential role of some bacterial metabolites of chloramphenicol (CAP) in CAP-induced hematotoxicity, we examined their cytotoxic effects on bone marrow cells in vitro using a number of cytotoxicity parameters. Among the metabolites tested, dehydro-CAP (DHCAP) and p-nitrophenyl-2-amino-3 hydroxypropanone-HCI (NPAP) were more toxic than CAP. DHCAP was at least as toxic as nitroso-CAP. At concentrations of ≤ 10-4 mol/L, DHCAP caused total irreversible inhibition of myeloid colony (CFU-GM) growth and 80% inhibition of DNA synthesis in human bone marrow. Incubation of human bone marrow cells with 10-4 mol/L nitroso-CAP or DHCAP for 24 hours resulted in 75% and 65% cell death respectively. Although DHCAP was 10- to 20-fold more cytotoxic than CAP, it was only one third as effective in inhibiting mitochondrial protein synthesis, indicating that DHCAP exerts its toxic effect by alternate mechanisms. The cytotoxicity of DHCAP and its relative stability, compared to the unstable nitroso CAP, suggest that this bacterial metabolite of CAP, and possibly others, may play a significant role in CAP-induced hematotoxicity.

Original languageEnglish
Pages (from-to)1180-1185
Number of pages6
JournalBlood
Volume70
Issue number4
StatePublished - Dec 1 1987

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Chloramphenicol
Metabolites
Bone
Bone Marrow
Wounds and Injuries
Poisons
Cytotoxicity
Bone Marrow Cells
Cells
Granulocyte-Macrophage Progenitor Cells
Mitochondrial Proteins
Cell death
Human computer interaction
Cell Death
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Jimenez, J. J., Arimura, G. K., Abou-Khalil, W. H., Isildar, M., & Yunis, A. A. (1987). Chloramphenicol-induced bone marrow injury: Possible role of bacterial metabolites of chloramphenicol. Blood, 70(4), 1180-1185.

Chloramphenicol-induced bone marrow injury : Possible role of bacterial metabolites of chloramphenicol. / Jimenez, Joaquin J; Arimura, G. K.; Abou-Khalil, W. H.; Isildar, M.; Yunis, Adel A.

In: Blood, Vol. 70, No. 4, 01.12.1987, p. 1180-1185.

Research output: Contribution to journalArticle

Jimenez, JJ, Arimura, GK, Abou-Khalil, WH, Isildar, M & Yunis, AA 1987, 'Chloramphenicol-induced bone marrow injury: Possible role of bacterial metabolites of chloramphenicol', Blood, vol. 70, no. 4, pp. 1180-1185.
Jimenez JJ, Arimura GK, Abou-Khalil WH, Isildar M, Yunis AA. Chloramphenicol-induced bone marrow injury: Possible role of bacterial metabolites of chloramphenicol. Blood. 1987 Dec 1;70(4):1180-1185.
Jimenez, Joaquin J ; Arimura, G. K. ; Abou-Khalil, W. H. ; Isildar, M. ; Yunis, Adel A. / Chloramphenicol-induced bone marrow injury : Possible role of bacterial metabolites of chloramphenicol. In: Blood. 1987 ; Vol. 70, No. 4. pp. 1180-1185.
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