Hemopoietic recovery from AZT toxicity with recombinant hemoglobin in a murine model of AIDS.
We studied the toxic effects of azidothymidine (AZT) on the hemopoietic colony growth (CFU-E, BFU-E and CFU-GM) of bone marrow in a murine model of AIDS (MAIDS). A sparing effect by recombinant hemoglobin (r-Hb) on AZT suppression of MAIDS bone marrow was found when 10 microM of r-Hb was included in bone marrow cultures. The AZT toxicity dose response curve showed that at a concentration of 0.1 microM, AZT inhibited CFU-E by 66%, BFU-E by 55% and CFU-GM by 67%. The addition of r-Hb (10 microM) to AZT-treated cultures stimulated CFU-E, BFU-E and CFU-GM by 89, 125 and 160%, respectively, as compared with AZT-treated (control). The addition of r-Hb to non AZT-treated cultures showed further stimulation of CFU-E, BFU-E and CFU-GM to 100, 160 and 187% of the control, respectively. These results indicate that exogenous r-Hb reverses AZT-induced hemopoietic toxicity and may prove to be useful in ameliorating AZT toxicity in immunosuppressive diseases.
Moqattash
S
S
Department of Human and Clinical Anatomy, Sultan Qaboos University, Muscat, Sultanate of Oman.
Lutton
J D
JD
Abu-Hijleh
M F
MF
Abraham
N G
NG
D000818:Animals; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006427:Hemin / Q000008:administration & dosage; D006454:Hemoglobins / Q000008:administration & dosage*; D051379:Mice; D016513:Mice, SCID; D016183:Murine Acquired Immunodeficiency Syndrome / Q000097:blood*; D011994:Recombinant Proteins / Q000008:administration & dosage; D015215:Zidovudine / Q000633:toxicity*
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D015215:Zidovudine; D006427:Hemin