Effects of antioxidants and a caspase inhibitor on chloramphenicol-inducedtoxicity of human bone marrow and HL-60 cells

Chloramphenicol (CAP), a board spectrum antibiotic widely used in many deve loping countries, has toxic side effects on bone marrow, the most serious o f which is aplastic anemia. Recent studies suggest that effects of CAP on s uppressing hematopoietic colony formation may be abrogated by antioxidants. lin addition, there is preliminary evidence that CAP induces apoptosis in hemopoietic stem cells, leading to aplastic anemia. We have been unable to demonstrate the protective effects of a variety of antioxidants on CAP-indu ced suppression of burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte/monocyte (CFU-GR;I). Using flow cytometry, we have, howeve r, confirmed that CAP can induce apoptosis in purified human bone marrow CD 34(+) cells. We also showed that a caspase inhibitor, Z-VAD.fmk, can amelio rate the apoptotic-inducing effects of CAP in the HL-60 cell line.