Neurotoxicological consequence of long-term exposure to lanthanum.
Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl(3)) through oral administration at 0, 0.1, 2 and 40mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40mg/kg LaCl(3) significantly inhibited the activity of Ca(2+)-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.
Feng
Liuxing
L
Key Laboratory of Nuclear Analytical Techniques, and Institute of High Energy Physics, Chinese Academy of Sciences, P.O. Box 918, Beijing 100049, China. meteorfeng@ihep.ac.cn
Xiao
Haiqing
H
He
Xiao
X
Li
Zijie
Z
Li
Fuliang
F
Liu
Nianqing
N
Zhao
Yuliang
Y
Huang
Yuying
Y
Zhang
Zhiyong
Z
Chai
Zhifang
Z
D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D007811:Lanthanum / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008670:Metals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013052:Spectrometry, X-Ray Emission; D013550:Swimming
D004785:Environmental Pollutants; D008670:Metals; C028521:lanthanum chloride; D007811:Lanthanum; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine