Department of Biology, King College, Bristol, Tennessee 37620, USA.
Toxicol Sci. 2011 Mar;120(1):146-53. doi: 10.1093/toxsci/kfq376. Epub 2010 Dec 22.
Manganese (Mn) is an essential metal required for normal homeostasis. Humans chronically exposed to high Mn levels, however, may exhibit psychomotor signs secondary to increased brain Mn. As Mn and iron (Fe) share several cellular membrane transporters, decreased Fe levels resulting from Fe deficiency or anemia lead to increased brain Mn deposition. Conversely, decreased Mn levels are associated with abnormal brain Fe accumulation. To reduce potential Mn toxicity resulting from brain Mn accumulation, we proposed that increased dietary Fe would attenuate brain Mn deposition. To test this hypothesis, three groups of Sprague-Dawley rats were injected weekly (14 weeks) with Mn (3 mg/kg) and fed normal Fe (TX), Fe-supplemented (FeS), or Fe-deficient (FeD) chow. Control (CN) rats received normal dietary Fe and saline injections. Using magnetic resonance imaging, rats were imaged biweekly for 14 weeks to qualitatively monitor brain Mn and Fe accumulation. Both FeS and FeD had greater brain Mn deposition than TX rats. By week 3, R(1) values, which correlate with Mn deposition, were statistically significantly increased (p < 0.05) in brain stem, cerebellum, cortex, midbrain, and striatum compared with CN or TX animals. By week 14, R(1) values for all brain regions in FeS and FeD animals were statistically significantly increased (p < 0.05). By the end of the study, similar results were obtained for R(2) values, a marker of Fe accumulation. These data suggest that Fe supplementation does not effectively protect and may even exacerbate brain Mn accumulation in mammals subchronically exposed to Mn.
锰 (Mn) 是一种维持正常体内平衡所必需的金属。然而，人类长期暴露于高水平的锰，可能会出现由于大脑中锰增加而导致的精神运动迹象。由于锰和铁 (Fe) 共享一些细胞膜转运体，铁缺乏或贫血导致的铁水平降低会导致大脑中锰的沉积增加。相反，锰水平降低与大脑中异常的铁积累有关。为了减少由于大脑中锰积累而导致的潜在锰毒性，我们提出增加膳食铁可以减轻大脑中锰的沉积。为了验证这一假设，三组 Sprague-Dawley 大鼠每周接受 Mn（3mg/kg）注射，并喂食正常 Fe（TX）、补充 Fe（FeS）或 Fe 缺乏（FeD）的饲料。对照（CN）大鼠接受正常饮食 Fe 和生理盐水注射。使用磁共振成像，对大鼠进行了 14 周的双周成像，以定性监测大脑中锰和铁的积累。与 TX 组相比，FeS 和 FeD 组的大脑中锰沉积量更大。到第 3 周时，与锰沉积相关的 R（1）值在脑干、小脑、皮层、中脑和纹状体中与 CN 或 TX 动物相比显著增加（p<0.05）。到第 14 周时，FeS 和 FeD 动物所有脑区的 R（1）值均显著增加（p<0.05）。在研究结束时，对于 R（2）值（铁积累的标志物）也得到了类似的结果。这些数据表明，在亚慢性暴露于锰的哺乳动物中，铁补充剂不仅不能有效保护，甚至可能加重大脑中锰的积累。
