Mameli O, Caria M A, Melis P, Zambenedetti P, Ramila M, Zatta P
Department of Biomedical Sciences, Human Physiology Division, V.le S. Pietro 43/B, 07100 Sassari, Italy.
Metab Brain Dis. 2006 Sep;21(2-3):89-107. doi: 10.1007/s11011-006-9010-9. Epub 2006 Jul 20.
The effects of chronic exposure (90 days) to Aluminum chloride (AlCl(3)) were analyzed in 3, 10 and 24 month old male rats (n=270) by investigating the function of the VOR (vestibulo-ocular reflex) in correlation with Aluminum (Al) concentrations in blood and brain. The VOR was chosen and tested in basal conditions (pre-exposure measures) and during the continuous administration of three different concentrations of AlCl(3) (0.5, 1, 2 g/l in drinking solution): the control animals being exposed to NaCl (0.125, 0.25 and 5 g/l in drinking solution). Results showed that LOAEL (Lowest Observed Adverse Effect Level) was 43.1+/-11.4 mg Al/kg-day. At this concentration the Al induced significant VOR impairment in all exposed rats, regardless of animal age. Neuroanatomical analysis showed that VOR impairment was not dependent on astrocyte damage nor evidences of amyloid deposits in the exposed rats was found. Significant changes of Al concentrations were observed in nervous tissue, while its concentration in whole blood was unaffected. Furthermore, results show that it is possible to identify an individual neurotoxic threshold for each animal and therefore hypothesize the clinical use of the VOR test for the evaluation of individual risk toxicity to chronic Al exposure.
通过研究前庭眼反射(VOR)功能与血液和大脑中铝(Al)浓度的相关性,分析了氯化铝(AlCl₃)慢性暴露(90天)对3、10和24月龄雄性大鼠(n = 270)的影响。选择VOR并在基础条件下(暴露前测量)以及连续给予三种不同浓度的AlCl₃(饮水中0.5、1、2 g/l)期间进行测试:对照动物暴露于NaCl(饮水中0.125、0.25和5 g/l)。结果表明,最低观察到有害作用水平(LOAEL)为43.1±11.4 mg Al/kg-天。在此浓度下,Al在所有暴露大鼠中均引起显著的VOR损伤,与动物年龄无关。神经解剖学分析表明,VOR损伤不依赖于星形胶质细胞损伤,且在暴露大鼠中未发现淀粉样沉积物的证据。在神经组织中观察到Al浓度有显著变化,而其在全血中的浓度未受影响。此外,结果表明有可能为每只动物确定个体神经毒性阈值,因此推测VOR测试可用于临床评估个体对慢性Al暴露的风险毒性。