Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell' Istria 65/1, 34137, Trieste, Italy.
University of Trieste, piazzale Europa 1, 34128, Trieste, Italy.
Inflammopharmacology. 2018 Feb;26(1):285-290. doi: 10.1007/s10787-017-0369-5. Epub 2017 Jun 23.
Alendronate (ALD), one among the nitrogen-containing bisphosphonates (NBPs), is currently used for the treatment of many pathological conditions. Unfortunately, although generally tolerated, NBPs treatment has been associated with central nervous system (CNS) adverse outcomes, such as amnesia, hallucinations and visual disturbances. So, we analyzed the effect of ALD treatment in glial cells, the main sources of cholesterol for neurons and principal cells involved in the immunological defense of the brain. We treated a glial cell line (U87-MG) with increasing doses of ALD (0.1, 1, 10, 25, 50 μM) for 48 h, aimed at evaluating the influence of this drug treatment on IL-1B expression, NLRP3 and CASP1 expression, mitochondrial activity and apoptotic cell death. We observed that ALD treatment, at the higher concentrations, induced a significant increase of IL-1B, NLRP3, CASP1 expression, provoked apoptosis and also mitochondrial damage in U87-MG. Considering the reported CNS adverse outcomes of NBPs treatment, our results confirm ALD side-effects on glial cell model.
阿仑膦酸钠(ALD)是一种含氮双膦酸盐(NBP),目前用于治疗许多病理状况。不幸的是,尽管通常可以耐受,但 NBP 治疗与中枢神经系统(CNS)不良后果有关,例如健忘、幻觉和视觉障碍。因此,我们分析了 ALD 治疗对神经细胞胆固醇主要来源的神经胶质细胞的影响,以及参与大脑免疫防御的主要细胞。我们用不同剂量的 ALD(0.1、1、10、25、50 μM)处理神经胶质细胞系(U87-MG)48 小时,旨在评估这种药物治疗对 IL-1B 表达、NLRP3 和 CASP1 表达、线粒体活性和细胞凋亡的影响。我们观察到,在较高浓度下,ALD 治疗诱导 U87-MG 中 IL-1B、NLRP3 和 CASP1 表达显著增加,引发细胞凋亡和线粒体损伤。考虑到 NBP 治疗的报道 CNS 不良后果,我们的结果证实了 ALD 对神经胶质细胞模型的副作用。