Protective Effect of Zinc Oxide Nanoparticles on Bisphenol S-Induced Cytotoxicity in Human Embryonal Testicular Carcinoma Cell Line.

Objective: Bisphenols are a type of phenolic chemical frequently used in producing various consumer products. Owing to their widespread exposure, these compounds can cause multiple toxic effects in humans. This study aimed to assess the protective effects of zinc oxide nanoparticles (ZnONPs) against bisphenol S (BPS)-induced cytotoxicity in the human testicular embryonic carcinoma cell line (NT2/D1).

Materials and methods: In this experimental study, cytotoxic concentrations of ZnONPs and BPS on NT2/D1 cells were optimized using the MTT assay. Thereafter, the effects of ZnONPs (50 and 500 μM), BPS (300 and 600 μM), and pre-treatment with ZnONPs (50 μM) followed by exposure to BPS (600 μM) on the expression of SOX2 and OCT4 genes and apoptosis-related proteins (i.e. Bax and Bcl-2) were evaluated, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively.

Results: Both BPS and ZnONPs reduced the viability of NT2/D1 cells in a time- and dose-dependent manner. Pretreatment with 50 μM of ZnONPs increased mRNA levels of SOX2 and OCT4 and improved the reduction of cell viability caused by exposure to half-maximal inhibitory concentration (IC₅₀) of BPS (P<0.001). In addition, pre-treatment with ZnONPs was able to suppress BPS-induced apoptosis, as evidenced by increased Bcl-2 (P<0.05) and decreased Bax (P<0.001) protein levels.

Conclusion: Although our findings indicate that short-term treatment with a low concentration of ZnONPs could have beneficial effects in preventing the cytotoxic effects of BPS by modulating the expression of apoptosis-related proteins and pluripotent genes in the NT2/D1 cells, further studies are recommended to confirm these results.