Silver nanoparticles (AgNPs) and zinc chloride (ZnCl2) exposure order determines the toxicity in C6 rat glioma cells

Silver nanoparticles (AgNPs) induced specific cell toxicity, and they are used as a tool for the study of several pathologies such as cancer. This work aimed to elucidate the toxic effect of < 10-nm silver nanoparticles (AgNPs) and zinc chloride (ZnCl2) in different administration orders on C6 rat glioma cells, as a biological model of study. C6 rat glioma cells were exposed to increasing concentrations of AgNPs (10–100 μg/mL) in the presence or absence of ZnCl2 (10–50 μg/mL) for 24 h. AgNPs or ZnCl2 as separate treatments decreased C6 rat glioma cell viability by 21% and 13%, respectively, versus the control, using the MTT assay. The administration of AgNPs (50 μg/mL) in the presence of ZnCl2 (10–50 μg/mL) was performed under two conditions: as pretreatment and as concomitant administration; both of them showed a significant decrease in the cell viability, around 30% and 90%, respectively. It was the concomitant treatment, which exerted the most significant effect on the viability decrease. We also observed that 24-h exposure to AgNPs increased cell populations (40%) in stages G0/G1 of the cell cycle, and decreased the number of cells (60%) in stages G2/M. However, in the concomitant treatment, as well as during induced cell death, the ZnCl2 pretreatment and concomitant treatment modified the cycle, increasing the S phase by 10%, suggesting that zinc (Zn) could be an essential regulator of the C6 rat glioma cell damage induced by AgNPs. This study will allow us to understand the mechanisms of cellular response to AgNPs, for the eventual study of these particles as a potential agent against cancer, such as glioblastoma multiforme.