O'Neal Stefanie L, Hong Lan, Fu Sherleen, Jiang Wendy, Jones Alexander, Nie Linda H, Zheng Wei
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Toxicol Lett. 2014 Aug 17;229(1):93-100. doi: 10.1016/j.toxlet.2014.06.019. Epub 2014 Jun 12.
Literature data indicate that bone is a major storage organ for manganese (Mn), accounting for 43% of total body Mn. However, the kinetic nature of Mn in bone, especially the half-life (t(1/2)), remained unknown. This study was designed to understand the time-dependence of Mn distribution in rat bone after chronic oral exposure. Adult male rats received 50 mg Mn/kg (as MnCl2) by oral gavage, 5 days per week, for up to 10 weeks. Animals were sacrificed every 2 weeks during Mn administration for the uptake study, and on day 1, week 2, 4, 8, or 12 after the cessation at 6-week Mn exposure for the t(1/2) study. Mn concentrations in bone (MnBn) were determined by AAS analysis. By the end of 6-week's treatment, MnBn appeared to reach the steady state (T(ss)) level, about 2-3.2 fold higher than MnBn at day 0. Kinetic calculation revealed t(1/2)s of Mn in femur, tibia, and humerus bone of 77 (r=0.978), 263 (r=0.988), and 429 (r=0.994) days, respectively; the average t(1/2) in rat skeleton was about 143 days, equivalent to 8.5 years in human bone. Moreover, MnBn were correlated with Mn levels in striatum, hippocampus, and CSF. These data support MnBn to be a useful biomarker of Mn exposure.
文献数据表明，骨骼是锰（Mn）的主要储存器官，占全身锰含量的43%。然而，锰在骨骼中的动力学特性，尤其是半衰期（t(1/2)），仍然未知。本研究旨在了解慢性口服暴露后大鼠骨骼中锰分布的时间依赖性。成年雄性大鼠通过口服灌胃给予50 mg Mn/kg（以MnCl2形式），每周5天，持续10周。在锰给药期间，每2周处死动物进行摄取研究，并在6周锰暴露停止后的第1天、第2周、第4周、第8周或第12周处死动物进行t(1/2)研究。通过原子吸收光谱分析测定骨骼中的锰浓度（MnBn）。在6周治疗结束时，MnBn似乎达到稳态（T(ss)）水平，比第0天的MnBn高约2 - 3.2倍。动力学计算显示，股骨、胫骨和肱骨中锰的t(1/2)分别为77天（r = 0.978）、263天（r = 0.988）和429天（r = 0.994）；大鼠骨骼中的平均t(1/2)约为143天，相当于人类骨骼中的8.5年。此外，MnBn与纹状体、海马体和脑脊液中的锰水平相关。这些数据支持MnBn作为锰暴露的有用生物标志物。
