Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Ankara, Turkey.
Faculty of Arts and Sciences, Department of Chemistry, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
J Appl Toxicol. 2022 Jun;42(6):981-994. doi: 10.1002/jat.4269. Epub 2021 Dec 7.
Short-chained alkyl mercury compounds accumulate in particularly in the brain. Exposure to these compounds is associated with various neurotoxic effects. Gender-based differences are observed in neurodevelopmental disorders, and testosterone and estradiol may alter the toxic effect of the compounds. The present study aimed to investigate the toxic effects of methylmercury and thimerosal on SH-SY5Y cells in high testosterone/low estradiol and high estradiol/low testosterone containing cellular environment and estimate whether male and female brains react differently to the toxic effects of methylmercury and thimerosal. Study groups (n = 3) were designed as control: growth medium, thimerosal (T): 1.15-μM thimerosal, methylmercury (M): 2.93-μM methylmercury, high testosterone/low estradiol + thimerosal (TT): 1-μM testosterone + 0.75-μM estradiol + 1.15-μM thimerosal, high estradiol/low testosterone + thimerosal (ET): 0.1-μM testosterone + 7.5-μM estradiol + 1.15-μM thimerosal, high testosterone/low estradiol + methylmercury (TM): 1-μM testosterone + 0.75-μM estradiol + 2.93-μM methylmercury and high estradiol/low testosterone + methylmercury (EM): 0.1-μM testosterone + 7.5-μM estradiol + 2.93-μM methylmercury. While a significant decrease in glutathione levels was observed in M group, it was not seen in EM group. A significant increase in the protein carbonyl levels was detected in T group. A similar increase was observed in the TM and TT groups in which testosterone was dominant. It was determined that methylmercury, but not thimerosal, caused significant DNA damage and in TT group. The results showed that both thimerosal and methylmercury are toxic on SH-SY5Y cells and toxic effects of methylmercury are more severe than thimerosal. It has been determined that testosterone and estradiol alter the toxic effects of thimerosal and methylmercury.
短链烷基汞化合物特别在大脑中积累。接触这些化合物与各种神经毒性作用有关。神经发育障碍存在性别差异,而睾酮和雌二醇可能会改变化合物的毒性作用。本研究旨在研究高睾酮/低雌二醇和高雌二醇/低睾酮细胞环境中甲基汞和硫柳汞对 SH-SY5Y 细胞的毒性作用,并评估男性和女性大脑对甲基汞和硫柳汞的毒性作用是否有不同反应。研究组(n=3)设计为对照组:生长培养基,硫柳汞(T):1.15-μM 硫柳汞,甲基汞(M):2.93-μM 甲基汞,高睾酮/低雌二醇+硫柳汞(TT):1-μM 睾酮+0.75-μM 雌二醇+1.15-μM 硫柳汞,高雌二醇/低睾酮+硫柳汞(ET):0.1-μM 睾酮+7.5-μM 雌二醇+1.15-μM 硫柳汞,高睾酮/低雌二醇+甲基汞(TM):1-μM 睾酮+0.75-μM 雌二醇+2.93-μM 甲基汞,高雌二醇/低睾酮+甲基汞(EM):0.1-μM 睾酮+7.5-μM 雌二醇+2.93-μM 甲基汞。虽然 M 组的谷胱甘肽水平显著下降,但 EM 组没有观察到。T 组的蛋白质羰基水平显著增加。在 TM 和 TT 组中观察到类似的增加,其中睾酮占主导地位。结果表明,只有甲基汞而不是硫柳汞会导致 SH-SY5Y 细胞的 DNA 损伤显著增加,且 TT 组中这种损伤更严重。结果表明,硫柳汞和甲基汞对 SH-SY5Y 细胞均有毒性,且甲基汞的毒性作用比硫柳汞更严重。已确定睾酮和雌二醇会改变硫柳汞和甲基汞的毒性作用。