CİNSİYETE DAYALI FARKLILIKLAR AÇISINDAN METİL CIVA VE TİYOMERSALİN TOKSİSİTELERİNİN İNSAN NÖROBLASTOMA HÜCRELERİNDE KARŞILAŞTIRMALI OLARAK DEĞERLENDİRİLMESİ

Abstract

Depending on exposure time and concentration, organic mercury compounds cause significant neurotoxic effects, ranging from deterioration in motor development and cognitive activities to severe neuromotor alterations. It is known that gender differences can lead to significant changes in the pathophysiology of many neurodegenerative disorders. In this thesis, it was aimed to investigate the neurotoxic effects of methyl mercury and thiomersal, a compound known to be metabolized to ethyl mercury, in human neuroblastoma cells. In addition, in the presence of organic mercury compounds, we aimed to determine the effects of testosterone and estradiol at different concentrations on possible neurotoxicity oxidative stress parameters, changes in the neuroendocrine system, oxidative DNA and RNA damage, cell death mechanisms and epigenetic changes. According to the results obtained from cytotoxicity experiments, the inhibitory concentration 20 (IC20) doses for thiomersal and methyl mercury were 1.15 and 2.93 µM, respectively. For 17β-estradiol, high and low doses were 7.5 and 0.75 µM whereas for testosterone 1 and 0.1 µM were used as high and low doses. Groups were designed as control, methyl mercury, thiomersal, high testosterone/low estradiol+thiomersal, high estradiol/low testosterone+thiomersal, high testosterone/low estradiol+methyl mercury, high estradiol/low testosterone+methyl mercury. It has been determined that both thiomersal and methyl mercury had toxic effects on neuroblastoma cells; the toxic effects of thiomersal specifically increased in high testosterone environment, the changes caused by estradiol and testosterone on thiomersal, and methyl mercury-induced toxic effects were different from each other, and that estradiol has a toxicity reducing effect generally. The results suggest that different neuronal responses may occur in males and females against organic mercury compounds.