Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat.
Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat.
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2,3-二羟基苯甲酸减轻眼镜蛇毒因子诱导的大鼠急性肺损伤。
DOI：
10.1164/arrd.1985.132.6.1288
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Kunkel,RG
中科院分区：
文献类型：
--
作者：
Baldwin,SR;Simon,RH;Boxer,LA;Till,GO;Kunkel,RG
中性粒细胞源性氧代谢产物被认为在多种疾病的急性肺损伤的发生中起重要作用。为了找到一种可能限制损伤的药物，我们评估了2，3-二羟基苯甲酸（DHB）的有益作用，DHB是一种已安全地作为铁螯合剂给予人类的药物。由于实验证据表明DHB可以作为自由基诱导反应的抑制剂，因此我们测试了其对大鼠静脉输注眼镜蛇毒因子（CVF）后发生的中性粒细胞依赖性肺损伤的保护作用。通过测定肺组织中125 I-白蛋白蓄积量的渗透性指数，我们发现DHB预处理可降低CVF处理大鼠的肺损伤（p < 0.05），并呈剂量依赖性。肺组织的形态学分析表明DHB的保护作用不是通过抑制CVF诱导的肺血管内中性粒细胞隔离引起的。由于铁饱和的DHB不能减轻肺损伤，并且体外实验表明DHB抑制铁-过氧化氢诱导的磷脂脂质体过氧化，我们怀疑DHB可能通过螯合铁来保护肺。我们的结论是，二羟基苯甲酸保护大鼠肺从眼镜蛇毒因子输注后发生的嗜中性粒细胞依赖性肺损伤。由于这种药物已被安全地用于人类，因此它可能具有预防急性肺损伤的潜力。
Neutrophil-derived oxygen metabolites are thought to play an important role in the genesis of acute lung injury in a variety of diseases. In an effort to find an agent that might limit the injury, we evaluated the beneficial effects of 2,3-dihydroxybenzoic acid (DHB), a drug that has been safely administered to humans as an iron-chelating agent. Because experimental evidence has demonstrated that DHB can act as an inhibitor of free radical-induced reactions, we tested its protective effect against the neutrophil-dependent lung injury that occurs in rats after the intravenous infusion of cobra venom factor (CVF). Using a permeability index that measures the amount of intravenously administered125I-albumin that accumulates in lung tissue, we found that pretreatment with DHB reduced (p < 0.05) the lung injury in CVF-treated rats in a dose-dependent manner. Morphometric analysis of lung tissue indicated that the protection by DHB was not caused by inhibition of CVF-induced neutrophil sequestration within the lung vasculature. Because iron-saturated DHB did not attenuate lung injury, and becausein vitroexperiments demonstrated that DHB inhibited iron-hydrogen peroxide-induced peroxidation of phospholipid liposomes, we suspect that DHB may be protecting the lung via chelation of iron. We conclude that dihydroxybenzoic acid protects the rat lung from the neutrophil-dependent lung injury that occurs after cobra venom factor infusion. Because this drug has been safely administered to humans, it may have potential as an agent to prevent acute lung injury.