Ferritin and desferrioxamine attenuate xanthine oxidase-dependent leak in isolated perfused rat lungs
Ferritin and desferrioxamine attenuate xanthine oxidase-dependent leak in isolated perfused rat lungs
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DOI：
10.1023/a:1016511611435
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发表时间：
2002-08-01
期刊：
影响因子：
5.1
通讯作者：
Repine, JE
中科院分区：
文献类型：
--
作者：
Hybertson, BM;Connelly, KG;Repine, JE
铁通过参与产生活性氧的反应，可能会导致急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）患者出现氧化性肺损伤。许多研究人员表明，患有 ALI 和 ARDS 的患者以及有患 ALI 和 ARDS 风险的患者血液中的内源性铁储存蛋白铁蛋白会增加，但这些增加的意义尚不清楚。在本研究中，我们测量了灌注黄嘌呤氧化酶（XO）和嘌呤（一种产生活性氧的酶系统）的离体大鼠肺中硫代巴比妥酸反应物质（TBARS）的肺组织水平和肺渗漏。我们发现，在血管灌注液溶液中添加铁蛋白 (100 ng/mL) 或去铁胺 (DFO，10 mM)（一种铁螯合剂）可减少灌注 XO 和嘌呤的离体大鼠肺中氧化剂引起的渗漏。添加铁蛋白或 DFO 还可降低灌注 XO 和嘌呤的离体大鼠肺中的 TBARS；然而，铁蛋白和 DFO 均不会降低体外 XO 活性。我们的结果表明，活性铁的可用性可能会改变氧化性肺渗漏，并且铁蛋白可能有助于防止氧化性肺损伤。
Iron, through its participation in reactions that generate reactive oxygen species, may contribute to the oxidative lung injury observed in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A number of investigators have shown that the endogenous iron storage protein ferritin increases in the blood of patients with and at-risk for ALI and ARDS, but the significance of these increases are not known. In the present investigation, we measured lung tissue levels of thiobarbituric acid reactive substances (TBARS) and lung leak in isolated rat lungs perfused with xanthine oxidase (XO) and purine, an enzymatic system which generates reactive oxygen species. We found that adding ferritin (100 ng/mL) or desferrioxamine (DFO, 10 mM), an iron chelator, to the vascular perfusate solution decreased oxidant-induced leak in isolated rat lungs perfused with XO and purine. Addition of ferritin or DFO also decreased TBARS in isolated rat lungs perfused with XO and purine; neither ferritin nor DFO, however, decreased XO activity in vitro. Our results suggest that oxidative lung leak may be altered by the availability of reactive iron and that ferritin may contribute to protection against oxidative lung injury.