Lanthanum (La) exposure can lead to learning and memory disorder in animals; however, the underlying mechanism of La induced neurotoxicity is still unknown. It has been demonstrated that Nrf2 activation by tert-butylhydroquinone (tBHQ) results in neuroprotection against brain injuries. However, little study has been done with respect to its effect on La induced neurotoxicity. Herein, experiments are undertaken to determine if there is a correlation between La damaged astrocytes and the Nrf2/ARE signalling pathway. Primary rat astrocytes are exposed to 0 mmol L⁻¹, 0.125 mmol L⁻¹, 0.25 mmol L⁻¹ and 0.5 mmol L⁻¹ lanthanum chloride (LaCl₃) for 24 hours. The results reveal that LaCl₃ increases the apoptosis/necrosis rate of astrocytes, decreases the glutathione (GSH) content, increases reactive oxygen species (ROS) levels and significantly down-regulates Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1 (NQO1), hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD₂), glutathione peroxidase 1 (GSH-Px₁), glutathione-s-transferase (GST) and γ-glutamine cysteine synthase (γ-GCS) in astrocytes. In addition, it is found that tBHQ displays an antagonistic effect on astrocytes damaged by LaCl₃. Therefore, La damaged astrocytes are possibly related to the down-regulated Nrf2/ARE pathway, and treatment with tBHQ clearly activates the Nrf2/ARE signalling pathway, which exerts protection against oxidative stress.

中文翻译：

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Nrf2 / ARE信号通路的激活减弱了氯化镧诱导的原代大鼠星形胶质细胞损伤

镧（La）暴露可导致动物学习和记忆障碍；然而，La诱导神经毒性的潜在机制仍是未知的。已经证明，叔丁基对苯二酚（t BHQ）激活Nrf2会导致针对脑损伤的神经保护作用。然而，关于其对La诱导的神经毒性的影响，尚未进行任何研究。在本文中，进行实验以确定在La损伤的星形胶质细胞和Nrf2 / ARE信号通路之间是否存在相关性。初级大鼠星形胶质细胞暴露于0毫摩尔大号^-1，0.125毫摩尔大号^-1，0.25毫摩尔大号^-1和0.5毫摩尔大号^-1氯化镧（的LaCl ₃）24小时。结果表明，LaCl ₃可增加星形胶质细胞的凋亡/坏死率，降低谷胱甘肽（GSH）含量，增加活性氧（ROS）水平并显着下调Nrf2以及Nrf2调控基因的mRNA和蛋白质表达。包括NADP（H）：脱氢酶醌1（NQO1），血红素加氧酶-1（HO-1），超氧化物歧化酶2（SOD ₂），谷胱甘肽过氧化物酶1（谷胱甘肽过氧化物酶₁），谷胱甘肽小号转移酶（GST）和星形胶质细胞中的γ-谷氨酰胺半胱氨酸合酶（γ-GCS）。另外，发现t BHQ对被LaCl ₃损伤的星形胶质细胞具有拮抗作用。。因此，La损伤的星形胶质细胞可能与下调的Nrf2 / ARE途径有关，而t BHQ的治疗明显激活了Nrf2 / ARE信号通路，从而对氧化应激起到保护作用。