Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats
Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats
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DOI：
10.1093/toxsci/60.2.242
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发表时间：
2001-04-01
影响因子：
3.8
通讯作者：
Wong, BA
中科院分区：
文献类型：
--
作者：
Dorman, DC;Struve, MF;Wong, BA
人们担心，相对缺锰或过多的人在吸入暴露后是否会增加锰中毒的风险。本研究的目的是确定体内锰负荷是否影响吸入硫酸锰(MnSO4)的药代动力学。出生后一天(PND)10只大鼠分别喂以低(2ppm)、足(10ppm)或高(100ppm)锰饲料。饲喂2ppm的锰饮食与许多效果有关，包括减少体重增加，降低升锰浓度，以及降低全身锰清除率。从PND77+/-2开始，雄性仔猪每天暴露6小时，连续14天暴露到0.092或0.92mgMnSO4/m(3)。测定暴露结束时的组织锰浓度和全身锰-54的清除率。暴露于0.092 mg MnSO4/m(3)的雄性大鼠与暴露于空气中的雄性大鼠相比，肺组织中的锰浓度升高。与暴露在空气中的雄性大鼠相比，暴露于0.92 mg MnSO4/m(3)的雄性大鼠的纹状体、肺和胆汁中的锰浓度增加。吸入MnSO4浓度与饲粮锰水平对组织锰浓度无显著交互作用。暴露于0.92mgMnSO4/m(3)的大鼠，与空气暴露的对照组相比，锰-54清除率增加，初始相消除半衰期缩短。这些结果表明，暴露于高水平吸入锰的轻度缺锰动物通过增加胆汁中的锰排泄来补偿。因此，他们似乎不会增加大脑中锰浓度升高的风险。
Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO4,). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liter manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO4/m(3). End-of-exposure tissue manganese concentrations and whole-body Mn-54 elimination rates were determined. Male rats exposed to 0.092 mg MnSO4/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO4/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO4 and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO4/m(3) also had increased Mn-54 clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.