Dey Mangaldeep, Singh Rakesh Kumar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli Transit Campus, Lucknow, Uttar Pradesh, India.
J Biochem Mol Toxicol. 2022 Dec;36(12):e23210. doi: 10.1002/jbt.23210. Epub 2022 Sep 3.
The risk of aluminium exposure to humans is very high as it may get into the human body through excessive dietary contaminants, inhalation of fine particulate matter, or through parenteral routes as a vaccine adjuvant and so forth. The increased level of aluminium in brain tissue has been shown to be associated with several neurodegenerative and neurotoxic adverse effects, including AD. However, the exact mechanism of aluminium-induced neurotoxicity is still unclear. Therefore, our study aimed to investigate the mechanism of neurotoxic and neurodegenerative effects through in vitro exposure of aluminium in rat glioma C6 cell line. The findings of our study have indicated that aluminium chloride exposure may lead to alteration in acetylcholine levels, increased oxidative imbalance and induction of molecular structural and functional markers of neuronal inflammation. This study also demonstrated that aluminium exposure may lead to the induction of caspase-3 along with apoptotic cell death and a significant increase in amyloid-beta and hyperphosphorylated tau levels in C6 cells. Thus, this study may provide a mechanistic understanding of the regulation of neuroinflammatory and neurodegenerative biomarkers due to aluminium exposure.
人类接触铝的风险非常高，因为铝可能通过过量的饮食污染物、吸入细颗粒物或作为疫苗佐剂等非肠道途径进入人体。脑组织中铝含量的增加已被证明与包括阿尔茨海默病（AD）在内的几种神经退行性和神经毒性不良反应有关。然而，铝诱导神经毒性的确切机制仍不清楚。因此，我们的研究旨在通过体外暴露大鼠胶质瘤C6细胞系于铝来研究神经毒性和神经退行性作用的机制。我们的研究结果表明，氯化铝暴露可能导致乙酰胆碱水平改变、氧化失衡增加以及神经元炎症分子结构和功能标志物的诱导。这项研究还表明，铝暴露可能导致C6细胞中caspase-3的诱导以及凋亡性细胞死亡，同时淀粉样β蛋白和过度磷酸化tau蛋白水平显著增加。因此，本研究可能为铝暴露导致的神经炎症和神经退行性生物标志物的调节提供机制性理解。
