Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E.
The ability of vitamin E (alpha-tocopherol) to stimulate erythroid progenitor cells was investigated in an attempt to identify ways to ameliorate zidovudine (azidothymidine, AZT)-induced anemia. In vitro, alpha-tocopherol acid succinate (ATS), upon incubation with murine bone marrow cells at concentrations of up to 4 micrograms/ml, caused a dose-dependent increase in erythroid colony-forming unit (CFU-E)-derived colonies. This increase was equivalent to the effect demonstrated by 50 mU of recombinant human erythropoietin (rhEpo) or 200 U of recombinant interleukin 3 (rIL-3). For in vivo studies, anemia was produced in CD-1 male mice by administering AZT in drinking water (1.5 mg/ml). Treatment with vitamin E (50 mg/kg body weight) or Epo (0.4 U per mouse) was initiated 24 h later and continued for five consecutive days. Seventh day bone marrow cells from femurs were assayed for CFU-E-derived colonies. Both vitamin E and Epo significantly increased the number of CFU-E-derived colonies by 75% and 86% of control, respectively, indicating that these agents were approximately similar in protecting the bone marrow from AZT-induced toxicity.
Gogu
S R
SR
Department of Pharmacology, Tulane University School of Medicine, New Orleans 70112.
Lertora
J J
JJ
George
W J
WJ
Hyslop
N E
NE
Agrawal
K C
KC
D000740:Anemia / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology / Q000633:toxicity*
D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D014810:Vitamin E; D015215:Zidovudine; D024505:Tocopherols