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Free radicals mediate amphetamine-induced acute pulmonary edema in isolated rat lung.

机译:自由基介导苯丙胺诱导的离体大鼠肺部急性肺水肿。

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Intravenous amphetamine abuse may cause serious cardiopulmonary complications via unknown mechanisms. We investigated the role of free radicals in the amphetamine-induced lung injury using isolated rat lungs. Adding amphetamine into the perfusate caused dose-dependent increases in perfusion pressure and lung weight. Amphetamine increased the filtration coefficient (K(f)) by 90 +/- 20% and 210 +/- 10% at doses of 10 microM and 50 microM, respectively, as compared to the baseline level. Pretreatment with dimethylthiourea (DMTU), an oxygen radical scavenger, abolished the pulmonary hypertension, lung weight gain, and permeability changes. We also examined the effect of amphetamine on free radical generation in polymorphonuclear leukocytes (PMN). Adding phorbol myristate acetate (PMA, 1 nM) enhanced the chemiluminescence indicating the functional viability of the isolated PMN. Amphetamine (50 microM) significantly enhanced the chemiluminescence generation of PMN by 152 +/- 26% as compared with the baseline value. Combination of amphetamine and PMA increased free radical formation by 360 +/- 85%. In summary, our results showed that amphetamine may cause acute lung injury by overproduction of free radicals. Although amphetamine can activate PMN, the source of free radicals remains to be determined.
机译:静脉内苯丙胺滥用可能通过未知机制引起严重的心肺并发症。我们使用分离的大鼠肺部研究了自由基在苯丙胺诱导的肺损伤中的作用。在灌流液中添加苯丙胺会导致灌注压力和肺重量的剂量依赖性增加。与基线水平相比,苯丙胺在10 microM和50 microM的剂量下分别使过滤系数(K(f))增加90 +/- 20%和210 +/- 10%。用二甲基硫脲(DMTU)(一种氧自由基清除剂)进行的预处理消除了肺动脉高压,肺增重和通透性变化。我们还检查了苯丙胺对多形核白细胞(PMN)自由基生成的影响。添加佛波肉豆蔻酸酯乙酸酯(PMA,1 nM)增强了化学发光,表明分离的PMN的功能可行性。与基线值相比,苯丙胺(50 microM)显着提高了PMN的化学发光生成152 +/- 26%。苯丙胺和PMA的组合可将自由基形成增加360 +/- 85%。总而言之,我们的结果表明,苯丙胺可能通过自由基的过量产生而导致急性肺损伤。尽管苯丙胺可以激活PMN,但自由基的来源仍有待确定。

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