Comparative evaluation of oxidative stress parameters the effects on bisphenol derivatives in HEPG2 cells

Bisphenols belong to a chemical group known as diphenylmethanes and widely used in the production of polycarbonate plastics, as basic chemicals in the resin coating of food and beverage tins. These substances are suggested to affect many basic physiological processes such as growth, stress response, gender development, reproduction ability, insulin production and utilization, and metabolic rate by disrupting the normal functioning of the endocrine system. There are many animal studies and limited number of in vitro studies in the literature evaluating the different effects of BPA exposure. The results of these studies have shown that BPA can have adverse health effects, and the use BPA is banned or restricted, particularly in different products used by children. Considering the potential adverse effects of BPA in recent years, alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) have begun to be used instead of BPA. In the last years, by taking into account the potential unwanted effects of BPA, different alternative bisphenols like bisphenol F (BPF) and bisphenol S (BPS) are being used instead of BPA. However, there is little information on the toxicity of alternative bisphenols and most of these information is limited only to the endocrine disrupting effects of these derivatives. The metabolism of BPS and BPF, their fate within the organism and the possible toxic substances have not been studied adequately. The possible toxic effects of BPA, BPF and BPS in HepG2 cells were evaluated comparatively by the research conducted In this thesis. For this purpose, the possible changes caused by bisphenols, like cytotoxicity and intracellular reactive oxygen species (ROS) and the effects on antioxidant/oxidant parameters, have been examined. In cytotoxicity experiments, the cytotoxicity potentials of different bisphenol derivatives was found to be as BPS> BPF> BPA according to the median inhibitor concentration (IC50) values . When the increase of intracellular ROS levels was evaluated, BPA and BPF caused significant and similar increases in intracellualr ROS production compared to control, while BPS also caused a significant increase compared to control; but the cytotoxicity induced by BPS was found to be significantly lower than BPA and BPF. In addition, BPA has increased superoxide dismutase (SOD) activity; but other bisphenols did not cause alterations in SOD activity. BPF and BPS treatments significantly decreased glutathione peroxidase (GPx) activity. No bisphenol derivative catalase (CAT) activity has significantly changed CAT activity. At the end of the study, we observed that the bisphenols used as alternatives to BPA, namely BPF and BPS, had similar toxic effects to BPA. Therefore new and different alternatives to BPA must be discovered and the toxic effects of these alternatives must be investigated in the future.