School of Health Sciences, Purdue University, 550 Stadium Mall Drive, CIVL-1163D, West Lafayette, IN 47907, USA.
Neurotoxicology. 2009 Nov;30(6):1214-22. doi: 10.1016/j.neuro.2009.02.005. Epub 2009 Feb 20.
A biomarker for detection of early onset neurobehavioral alterations in manganism remains unknown. The purpose of this study was to use a neurobehavioral test battery to identify subtle changes in Mn-induced motor and memory dysfunction and to relate the quantifiable neurological dysfunction to an established Mn-exposure index such as blood manganese-iron ratio (MIR). A total of 323 subjects were recruited to control (n=106), low-exposure (122), and high-exposure (95) groups. The test battery consisted of standard testing procedures including the nine-hole and groove-type steadiness tester, Benton visual retention test, and Purdue pegboard coordination test. No significant health problems or clinically diagnosed neurological dysfunctions were observed. Benton test did not reveal any abnormal memory deficits among Mn-exposed smelters, nor did the groove and nine-hole tests detect any abnormality in dynamic and static steadiness in tested subjects. Purdue pegboard test showed a remarkable age-related decline in fine movement coordination among all study participants regardless of the Mn-exposure condition. Mn exposure significantly exacerbated this age-related deterioration. Statistical modeling revealed that the plasma and erythrocyte MIR (i.e., pMIR and eMIR, respectively) were associated with Purdue pegboard scores. Among all subjects whose MIR were above the cut-off value (COV), pMIR was significantly correlated with pegboard scores (r=-0.261, p=0.002), whereas for those subjects over the age of 40, the eMIR, but not pMIR, was associated with declined pegboard performance (r=-0.219, p=0.069). When both factors were taken into account (i.e., age>40 and MIR>the COV), only pMIR was inversely associated with pegboard scores. Combining their usefulness in Mn-exposure assessment, we recommend that the blood Mn-Fe ratio may serve as a reasonable biomarker not only for assessment of Mn exposure but also for health risk assessment.
一种用于检测锰中毒早期神经行为改变的生物标志物仍不清楚。本研究旨在使用神经行为测试组合来识别 Mn 诱导的运动和记忆功能障碍的细微变化,并将可量化的神经功能障碍与已建立的 Mn 暴露指数(如血锰铁比 (MIR))相关联。共招募了 323 名受试者作为对照组(n=106)、低暴露组(n=122)和高暴露组(n=95)。测试组合包括标准测试程序,包括九孔和槽型稳定性测试器、本顿视觉保持测试和普渡钉板协调测试。在 Mn 暴露的冶炼工人中,本顿测试并未发现任何异常的记忆缺陷,槽和九孔测试也未检测到测试对象在动态和静态稳定性方面的任何异常。普渡钉板测试显示,所有研究参与者的精细运动协调能力都随着年龄的增长而显著下降,无论 Mn 暴露情况如何。Mn 暴露显著加剧了这种与年龄相关的恶化。统计模型表明,血浆和红细胞 MIR(即 pMIR 和 eMIR)与普渡钉板分数相关。在所有 MIR 高于截止值 (COV) 的受试者中,pMIR 与钉板分数显著相关(r=-0.261,p=0.002),而对于年龄超过 40 岁的受试者,eMIR 而非 pMIR 与钉板性能下降相关(r=-0.219,p=0.069)。当同时考虑这两个因素(即年龄>40 岁和 MIR>COV)时,只有 pMIR 与钉板分数呈负相关。结合它们在 Mn 暴露评估中的有用性,我们建议血锰铁比不仅可以作为评估 Mn 暴露的合理生物标志物,还可以作为健康风险评估的生物标志物。