Iacobini M, Palumbo G, Cassiani F, Perla F M, Werner B, Menichelli A, Del Principe D
Institute of Pediatrics, La Sapienza, University of Rome, Italy.
Haematologica. 1997 Jul-Aug;82(4):411-4.
Anecdotal reports in patients with acute and chronic iron overload have recently indicated that the efficacy and safety of an alternative chelation program including intravenous and/or continuous delivery of deferoxamine (DFO) may be in contrast with the risk of developing lung injury. Production of oxygen radicals has been postulated to be an important mechanism by which polymorphonuclear leukocytes (PMNs) could cause tissue injury in patients undergoing this alternative treatment method.
PMNs obtained from healthy donors were incubated at 37 degrees C for 30 min with DFO (across the drug concentration 0.125 to 10 mg/mL). Superoxide (O2) production was measured by superoxide inhibitable cytochrome c reduction as well as by an NBT densitometric kinetic test. In the same run the effect of lipid peroxidation was demonstrated by means of a malonyl-dialdehyde (MDA) assay.
Preincubation of PMNs with any study concentration of DFO significantly enhanced O2 release as well as MDA production upon PMA stimulation. Maximal intracellular and extracellular O2-release as well as MDA production occurred at certain drug concentrations.
Our in vitro findings suggest that O2-release may be an additional detrimental contribution to tissue injury in some patients who develop pulmonary toxic effects while on intravenous and/or continuous DFO administration.
近期针对急慢性铁过载患者的个案报道表明，一种包含静脉注射和/或持续输注去铁胺（DFO）的替代螯合方案的疗效与安全性，可能与发生肺损伤的风险相悖。氧自由基的产生被假定为多形核白细胞（PMN）在接受这种替代治疗方法的患者中导致组织损伤的一种重要机制。
将从健康供体获取的PMN在37℃下与DFO（药物浓度范围为0.125至10mg/mL）孵育30分钟。通过超氧化物可抑制的细胞色素c还原以及NBT密度测定动力学试验来测量超氧化物（O₂）的产生。在同一实验中，通过丙二醛（MDA）测定来证明脂质过氧化的作用。
PMN与任何研究浓度的DFO预孵育后，在佛波酯（PMA）刺激下均显著增强了O₂释放以及MDA产生。在特定药物浓度下出现了最大的细胞内和细胞外O₂释放以及MDA产生。
我们的体外研究结果表明，对于一些在静脉注射和/或持续给予DFO时出现肺部毒性作用的患者，O₂释放可能是对组织损伤的另一种有害作用。
