Moqattash S, Lutton J D, Abu-Hijleh M F, Abraham N G
Department of Human and Clinical Anatomy, Sultan Qaboos University, Muscat, Sultanate of Oman.
Acta Haematol. 1994;92(4):182-6. doi: 10.1159/000204217.
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.
我们在艾滋病小鼠模型(MAIDS)中研究了叠氮胸苷(AZT)对骨髓造血集落生长(CFU-E、BFU-E和CFU-GM)的毒性作用。当在骨髓培养物中加入10微摩尔的重组血红蛋白(r-Hb)时,发现r-Hb对AZT抑制MAIDS骨髓具有保护作用。AZT毒性剂量反应曲线表明,在浓度为0.1微摩尔时,AZT抑制CFU-E达66%,BFU-E达55%,CFU-GM达67%。与AZT处理组(对照组)相比,向经AZT处理的培养物中添加r-Hb(10微摩尔)分别使CFU-E、BFU-E和CFU-GM增加了89%、125%和160%。向未经AZT处理的培养物中添加r-Hb分别使CFU-E、BFU-E和CFU-GM进一步增加至对照组的100%、160%和187%。这些结果表明,外源性r-Hb可逆转AZT诱导的造血毒性,可能被证明对改善免疫抑制疾病中的AZT毒性有用。