Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats
Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats
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DOI：
10.1152/ajplung.00382.2004
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发表时间：
2005-05-01
影响因子：
4.9
通讯作者：
Wessling-Resnick, M
中科院分区：
文献类型：
--
作者：
Heilig, E;Molina, R;Wessling-Resnick, M
空气中高浓度的锰可能具有神经毒性，但人们对这种金属通过肺部的吸收知之甚少。肠道锰摄取因缺铁而上调，并被认为是由二价金属转运蛋白1 （DMT1）介导的，二价金属转运蛋白1是一种已知在膳食铁吸收中起作用的铁调节因子。为了更好地表征金属从肺到血液的吸收，并检测缺铁是否可能改变这一过程，我们比较了正常大鼠和缺铁大鼠肺锰和铁吸收的药代动力学。测定肺中DMT1表达水平，以探索铁缺乏引起的可能改变金属吸收的潜在变化。气管内灌注Mn-54和Fe-59的药代动力学曲线有显著差异，提示两种金属的肺摄取机制不同。气管内灌注铁缺乏大鼠血液中Mn-54水平显著升高，而血液中Fe-59水平与对照组相比显著降低。当通过静脉注射放射性同位素时，观察到同样的趋势，表明缺铁的大鼠改变了血液对锰的清除。原位分析显示在气道上皮中存在DMT1转录本；然而，mRNA水平在缺铁时没有变化。尽管肺DMT1水平和金属吸收似乎不受缺铁的影响，但本研究确定的血液中灌注锰清除率的差异支持了铁状态可以影响这种金属的潜在毒性的观点。
High levels of airborne manganese can be neurotoxic, yet little is known about absorption of this metal via the lungs. Intestinal manganese uptake is upregulated by iron deficiency and is thought to be mediated by divalent metal transporter 1 (DMT1), an iron-regulated factor known to play a role in dietary iron absorption. To better characterize metal absorption from the lungs to the blood and test whether iron deficiency may modify this process, the pharmacokinetics of pulmonary manganese and iron absorption by control and iron-deficient rats were compared. Levels of DMT1 expression in the lungs were determined to explore potential changes induced by iron deficiency that might alter metal absorption. The pharmacokinetic curves for intratracheally instilled Mn-54 and Fe-59 were significantly different, suggesting that pulmonary uptake of the two metals involves different mechanisms. Intratracheally instilled iron-deficient rats had significantly higher blood Mn-54 levels, whereas blood Fe-59 levels were significantly reduced compared with controls. The same trend was observed when radioisotopes were delivered by intravenous injection, indicating that iron-deficient rats have altered blood clearance of manganese. In situ analysis revealed the presence of DMT1 transcripts in airway epithelium; however, mRNA levels did not change in iron deficiency. Although lung DMT1 levels and metal absorption did not appear to be influenced by iron deficiency, the differences in blood clearance of instilled manganese identified by this study support the idea that iron status can influence the potential toxicity of this metal.