TY - JOUR
T1 - Interaction of chloramphenicol and metabolites with colony stimulating factors
T2 - Possible role in chloramphenicol-induced bone marrow injury
AU - Jimenez, J. J.
AU - Jimenez, J. G.
AU - Daghistani, D.
AU - Yunis, A. A.
PY - 1990/1/1
Y1 - 1990/1/1
N2 - We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10-4 M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10-7 M), nitroso-CAP (NO-CAP) (60% at 5 x 10-6 M) and NPAP (35% at 10-5 M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10-6 M) and NO-CAP (5 x 10-6 M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia.
AB - We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10-4 M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10-7 M), nitroso-CAP (NO-CAP) (60% at 5 x 10-6 M) and NPAP (35% at 10-5 M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10-6 M) and NO-CAP (5 x 10-6 M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia.
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U2 - 10.1097/00000441-199012000-00002
DO - 10.1097/00000441-199012000-00002
M3 - Article
C2 - 2264572
AN - SCOPUS:0025641280
VL - 300
SP - 350
EP - 353
JO - American Journal of the Medical Sciences
JF - American Journal of the Medical Sciences
SN - 0002-9629
IS - 6
ER -