4.5 Article

Modification of the toxic effects of methylmercury and thimerosal by testosterone and estradiol in SH-SY5Y neuroblastoma cell line

Journal

JOURNAL OF APPLIED TOXICOLOGY
Volume 42, Issue 6, Pages 981-994

Publisher

WILEY
DOI: 10.1002/jat.4269

Keywords

apoptosis; estradiol; methylmercury; neurotoxicity; oxidative stress; testosterone; thimerosal

Categories

Funding

  1. Hacettepe University Research Fund [TDK-2020-18502, 18502]

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Short-chained alkyl mercury compounds accumulate in the brain, associated with various neurotoxic effects. Gender-based differences in neurodevelopmental disorders may be influenced by testosterone and estradiol altering the toxic effect of these compounds. The study found that both thimerosal and methylmercury are toxic to SH-SY5Y cells, with methylmercury showing more severe toxic effects.
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-mu M thimerosal, methylmercury (M): 2.93-mu M methylmercury, high testosterone/low estradiol + thimerosal (TT): 1-mu M testosterone + 0.75-mu M estradiol + 1.15-mu M thimerosal, high estradiol/low testosterone + thimerosal (ET): 0.1-mu M testosterone + 7.5-mu M estradiol + 1.15-mu M thimerosal, high testosterone/low estradiol + methylmercury (TM): 1-mu M testosterone + 0.75-mu M estradiol + 2.93-mu M methylmercury and high estradiol/low testosterone + methylmercury (EM): 0.1-mu M testosterone + 7.5-mu M estradiol + 2.93-mu M 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.

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