Overexposure to manganese (Mn) or iron (Fe) may lead to neurological damage. The aim of this study was to investigate the effects of subchronic Mn and Fe exposure, alone or in combination, on the distribution of other elements and the relationship between Mn and Fe levels in whole blood and brain. Forty male Sprague-Dawley (SD) rats were divided into control, Mn-exposed, Fe-exposed, and combined Mn-Fe-exposed groups, with 10 rats assigned randomly to each group. The control, Mn-exposed, Fe-exposed group and the combined Mn-Fe-exposed groups were injected intraperitoneally with equal amounts of saline, 5 mg/kg MnCl2, 20 mg/kg FeSO4 or 5 mg/kg MnCl2+20 mg/kg FeSO4 once a day, 5 days a week for 8 weeks. The levels of Mn, Fe and other metallic elements [including barium (Ba), beryllium (Be), strontium (Sr), antimony (Sb), lead (Pb), vanadium (V) and copper (Cu)] in whole blood and brain tissue (including the globus pallidus, hippocampus, striatum and substantia nigra) were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The results of this study show that, in whole blood, Mn levels were increased (p < 0.05) in the Mn-exposed group, Fe levels were decreased in both the Fe-exposed (p < 0.05) and Mn-exposed groups (p < 0.01), and Sb levels were increased in both the Mn-exposed and combined Mn-Fe-exposed groups (p < 0.05). In the substantia nigra, the levels of Be (p < 0.01), Sr (p < 0.05), and Cu (p < 0.001) were increased in the Fe-exposed group; the levels of Cu were also significantly increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001); the levels of V were decreased (p < 0.05) in the combined Mn-Fe-exposed group; and the levels of V were decreased in the Fe-exposed group (p < 0.01 ), Mn-exposed group (p < 0.05) and combined Mn-Fe-exposed group (p < 0.001) had decreased Ba levels. In the pallidum, Fe levels were increased in the Mn-Fe co-exposed group (p < 0.0001); Ba (p < 0.01) and Pb (p < 0.05) levels were decreased in the Fe-exposed group; Ba (p < 0.05) levels were decreased in the Mn-exposed group; and Ba levels were increased in the Mn-Fe co-exposed group (p < 0.05). In the hippocampus, Mn (p < 0.01), Cu (p < 0.05), Sb (p < 0.01), and V (p < 0.05) levels were increased in the Fe-exposed group; Mn levels were increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001). In the striatum, Be levels were decreased in the Mn-Fe combined exposure group (p < 0.05). Mn and Fe levels in whole blood and brain tissue can reflect the accumulation of Mn and Fe. These measurements can serve as valuable predictive biomarkers for subchronic Mn or Fe exposure and combined Mn-Fe exposure. The interactions between Mn and Fe and the distribution and abnormalities of the essential metal elements in the central nervous system and other organs need to be further investigated.

Effects of Subchronic Manganese and Iron Exposure, Alone or in Combination, on Elemental Distribution in Rats

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发表日期：

2025年4月22日

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Yan Li,
Jian-chao Peng,
Yuan-yuan Fang,
Li-mei Qin,
Michael Aschner,
Yue-ming Jiang

摘要

Overexposure to manganese (Mn) or iron (Fe) may lead to neurological damage. The aim of this study was to investigate the effects of subchronic Mn and Fe exposure, alone or in combination, on the distribution of other elements and the relationship between Mn and Fe levels in whole blood and brain. Forty male Sprague-Dawley (SD) rats were divided into control, Mn-exposed, Fe-exposed, and combined Mn-Fe-exposed groups, with 10 rats assigned randomly to each group. The control, Mn-exposed, Fe-exposed group and the combined Mn-Fe-exposed groups were injected intraperitoneally with equal amounts of saline, 5 mg/kg MnCl₂, 20 mg/kg FeSO₄ or 5 mg/kg MnCl₂+20 mg/kg FeSO₄ once a day, 5 days a week for 8 weeks. The levels of Mn, Fe and other metallic elements [including barium (Ba), beryllium (Be), strontium (Sr), antimony (Sb), lead (Pb), vanadium (V) and copper (Cu)] in whole blood and brain tissue (including the globus pallidus, hippocampus, striatum and substantia nigra) were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The results of this study show that, in whole blood, Mn levels were increased (p < 0.05) in the Mn-exposed group, Fe levels were decreased in both the Fe-exposed (p < 0.05) and Mn-exposed groups (p < 0.01), and Sb levels were increased in both the Mn-exposed and combined Mn-Fe-exposed groups (p < 0.05). In the substantia nigra, the levels of Be (p < 0.01), Sr (p < 0.05), and Cu (p < 0.001) were increased in the Fe-exposed group; the levels of Cu were also significantly increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001); the levels of V were decreased (p < 0.05) in the combined Mn-Fe-exposed group; and the levels of V were decreased in the Fe-exposed group (p < 0.01 ), Mn-exposed group (p < 0.05) and combined Mn-Fe-exposed group (p < 0.001) had decreased Ba levels. In the pallidum, Fe levels were increased in the Mn-Fe co-exposed group (p < 0.0001); Ba (p < 0.01) and Pb (p < 0.05) levels were decreased in the Fe-exposed group; Ba (p < 0.05) levels were decreased in the Mn-exposed group; and Ba levels were increased in the Mn-Fe co-exposed group (p < 0.05). In the hippocampus, Mn (p < 0.01), Cu (p < 0.05), Sb (p < 0.01), and V (p < 0.05) levels were increased in the Fe-exposed group; Mn levels were increased in the Mn-exposed group (p < 0.01) and the combined Mn-Fe-exposed group (p < 0.0001). In the striatum, Be levels were decreased in the Mn-Fe combined exposure group (p < 0.05). Mn and Fe levels in whole blood and brain tissue can reflect the accumulation of Mn and Fe. These measurements can serve as valuable predictive biomarkers for subchronic Mn or Fe exposure and combined Mn-Fe exposure. The interactions between Mn and Fe and the distribution and abnormalities of the essential metal elements in the central nervous system and other organs need to be further investigated.