Action of deferoxamine against Pneumocystis carinii.
Action of deferoxamine against Pneumocystis carinii.
复制标题
去铁胺对卡氏肺孢子虫的作用。
DOI：
10.1128/aac.45.12.3560-3565.2001
复制
发表时间：
2001
影响因子：
4.9
通讯作者：
Merali,S
中科院分区：
文献类型：
--
作者：
ClarksonJr,AB;Turkel-Parrella,D;Williams,JH;Chen,LC;Gordon,T;Merali,S
我们早先发现，去铁胺（DFO），一种用于治疗铁超载的药物，对卡氏肺孢子虫（PCP）大鼠模型有活性。我们曾假设通过剥夺营养铁的作用模式;然而，这里的数据显示DFO穿透卡氏肺吸虫，造成不可逆的损伤，因此表明不同的作用模式。通过高压液相色谱分析显示DFO吸收来证明渗透。以钙黄绿素-AM为指示剂，DFO暴露可引起胞浆游离铁减少。体外暴露于≥100 μM DFO ≥8 h导致生长停止，细胞数量在数天内下降。这种对卡氏肺孢子虫的直接和不可逆的损害导致了这样的预测，即通过气溶胶向肺部不频繁地递送DFO将是PCP动物模型的有效治疗。通过证明每周一次的大鼠气雾剂治疗作为PCP大鼠模型的预防性和治疗性治疗均100%有效，证实了这一预测。
We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model ofPneumocystis cariniipneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetratesP.carinii, causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction inP.cariniicytoplasmic free iron. Exposure to ≥100 μM DFO for ≥8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage toP.cariniiled to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.