Neurotoxicity and brain localization of europium doped Gd2O3 nanotubes in rats after intranasal instillation
来源期刊：JOURNAL OF RARE EARTHS2017年第11期
论文作者：Huifang Liu Wencong Zhao Xiaochun Wang Guang Jia Yi Jin Kun Ge Huanyun Ma Jinchao Zhang
文章页码：1126 - 1132
摘 要：Europium doped Gd2 O3 nanotubes(Gd2 O3:Eu3+ NTs) were synthesized and characterized. Then,the neurotoxicity and brain localization of Gd2 O3:Eu3+ NTs were evaluated. All experimental rats were administered by intranasal instillation with 30 μL Gd2 O3:Eu3+ NTs suspension 3.0 and 15.0 mg/mL respectively every other day for 35 consecutive days, and the rats of control group were administered with an equal volume of physiological saline. The Morris water maze was used to assess the rats’ spatial learning and memory ability. The oxidative stress-related biomarkers and the activity of AChE in striatum and hippocampus were analyzed, and the histopathology of hippocampus and striatum was observed.The brain localization of gadolinium（Gd） was measured. The results showed that the escape latency of the rats in high-dose group prolonged significantly compared with that of control group after treatment of six weeks（p < 0.05）, and the swimming time in D quadrant of high-dose group shortened significantly compared with the control group（p < 0.01）. In addition, high-dose Gd2 O3:Eu3+ NTs could decrease the activity of GSH-Px and CAT in hippocampus and the activity of SOD in striatum（p < 0.05）. MDA content in hippocampus and striatum of high-dose group increased（p < 0.05）. High dose Gd2 O3:Eu3+ NTs could increase the activity of AChE in hippocampus（p < 0.05） and in striatum（p < 0.001）. But there were no significant differences between the low-dose group and control group（p > 0.05）. The results of Gd localization in brain showed that the ranking of Gd levels was olfactory bulb > striatum > hippocampus> cerebellum > brain stem > frontal cortex. The pathology results indicated that high dose Gd2 O3:Eu3+NTs resulted in degeneration necrosis, nucleus pycnosis, and axons disappearance of the nerve cells at CA1, CA3 and DG area of hippocampus. Therefore, the results implied that Gd2 O3:Eu3+ NTs have the potential neurotoxicity and a possible danger in causing neurodegenerative disorders after intranasal instillation.
Huifang Liu1，Wencong Zhao1，Xiaochun Wang2，Guang Jia3，Yi Jin4，Kun Ge3，Huanyun Ma4，Jinchao Zhang3
1. College of Pharmaceutical Science, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University2. Affiliated Hospital of Hebei University3. College of Chemistry & Environmental Science,Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, Hebei University4. College of Basic Medical Science,Hebei University
摘 要：Europium doped Gd2 O3 nanotubes(Gd2 O3:Eu3+ NTs) were synthesized and characterized. Then,the neurotoxicity and brain localization of Gd2 O3:Eu3+ NTs were evaluated. All experimental rats were administered by intranasal instillation with 30 μL Gd2 O3:Eu3+ NTs suspension 3.0 and 15.0 mg/mL respectively every other day for 35 consecutive days, and the rats of control group were administered with an equal volume of physiological saline. The Morris water maze was used to assess the rats’ spatial learning and memory ability. The oxidative stress-related biomarkers and the activity of AChE in striatum and hippocampus were analyzed, and the histopathology of hippocampus and striatum was observed.The brain localization of gadolinium（Gd） was measured. The results showed that the escape latency of the rats in high-dose group prolonged significantly compared with that of control group after treatment of six weeks（p < 0.05）, and the swimming time in D quadrant of high-dose group shortened significantly compared with the control group（p < 0.01）. In addition, high-dose Gd2 O3:Eu3+ NTs could decrease the activity of GSH-Px and CAT in hippocampus and the activity of SOD in striatum（p < 0.05）. MDA content in hippocampus and striatum of high-dose group increased（p < 0.05）. High dose Gd2 O3:Eu3+ NTs could increase the activity of AChE in hippocampus（p < 0.05） and in striatum（p < 0.001）. But there were no significant differences between the low-dose group and control group（p > 0.05）. The results of Gd localization in brain showed that the ranking of Gd levels was olfactory bulb > striatum > hippocampus> cerebellum > brain stem > frontal cortex. The pathology results indicated that high dose Gd2 O3:Eu3+NTs resulted in degeneration necrosis, nucleus pycnosis, and axons disappearance of the nerve cells at CA1, CA3 and DG area of hippocampus. Therefore, the results implied that Gd2 O3:Eu3+ NTs have the potential neurotoxicity and a possible danger in causing neurodegenerative disorders after intranasal instillation.
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