Effects of antioxidants and a caspase inhibitor on chloramphenicol-induced toxicity of human bone marrow and HL-60 cells.
Chloramphenicol (CAP), a board spectrum antibiotic widely used in many developing countries, has toxic side effects on bone marrow, the most serious of which is aplastic anemia. Recent studies suggest that effects of CAP on suppressing hematopoietic colony formation may be abrogated by antioxidants. In 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-induced suppression of burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte/monocyte (CFU-GM). Using flow cytometry, we have, however, confirmed that CAP can induce apoptosis in purified human bone marrow CD34+ cells. We also showed that a caspase inhibitor, Z-VAD.fmk, can ameliorate the apoptotic-inducing effects of CAP in the HL-60 cell line.
Kong
C T
CT
Department of Pathology, The University of Hong Kong, China.
Holt
D E
DE
Ma
S K
SK
Lie
A K
AK
Chan
L C
LC
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D018952:Antigens, CD34 / Q000032:analysis; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D002701:Chloramphenicol / Q000633:toxicity*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018922:HL-60 Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans
D000590:Amino Acid Chloromethyl Ketones; D000900:Anti-Bacterial Agents; D018952:Antigens, CD34; D000975:Antioxidants; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D002701:Chloramphenicol