Louie S, Arata M A, Offerdahl S D, Halliwell B
Department of Internal Medicine, School of Medicine, University of California, Davis 95616-8542.
J Lab Clin Med. 1993 Mar;121(3):502-9.
To test the hypothesis that deferoxamine (DFO) may protect the lung against the acute toxicity of ozone (O3), male Sprague-Dawley rats (250 to 300 gm) were tracheally insufflated before exposure to O3 (2 ppm for 4 hours) with DFO (25 mg/kg), ferric-DFO, or sterile water. Measurements of bronchoalveolar lavage fluid (BALF) protein, ascorbate, hydrogen peroxide, and lipid hydroperoxides were made immediately after O3 exposure and 12 and 24 hours later. DFO (25 mg/kg) decreased BALF protein concentration (p < 0.05) and was associated with higher BALF ascorbate concentrations (p < 0.01) in O3-exposed animals. Ferric-DFO did not show these protective effects. No peroxides were found in BALF from any control or O3-exposed animals (detection limit: H2O2, 1 pmol; lipid hydroperoxides, 0.3 pmol). Higher DFO doses (50 mg/kg and 100 mg/kg) did not decrease BALF protein concentration immediately after O3 exposure or 12 hours later. Indeed, the highest dose was toxic to O3-exposed animals. Although DFO is able to protect against O3-induced lung damage in rats, apparently by chelating iron, its effect dose range appears to be narrow.
为了验证去铁胺（DFO）可能保护肺部免受臭氧（O3）急性毒性影响的假说，将体重250至300克的雄性Sprague-Dawley大鼠在暴露于O3（2 ppm，持续4小时）之前经气管注入DFO（25毫克/千克）、铁-去铁胺或无菌水。在O3暴露后即刻以及12小时和24小时后，对支气管肺泡灌洗液（BALF）中的蛋白质、抗坏血酸盐、过氧化氢和脂质氢过氧化物进行了测量。DFO（25毫克/千克）降低了O3暴露动物的BALF蛋白质浓度（p < 0.05），并与较高的BALF抗坏血酸盐浓度相关（p < 0.01）。铁-去铁胺未显示出这些保护作用。在任何对照组或O3暴露动物的BALF中均未发现过氧化物（检测限：H2O2，1皮摩尔；脂质氢过氧化物，0.3皮摩尔）。较高剂量的DFO（50毫克/千克和100毫克/千克）在O3暴露后即刻或12小时后并未降低BALF蛋白质浓度。实际上，最高剂量对O3暴露动物有毒性。尽管DFO显然通过螯合铁能够保护大鼠免受O3诱导的肺损伤，但其有效剂量范围似乎较窄。
