Abstract
Endocrine disrupting chemicals (EDCs) may affect many biological processes like growth and stress response. Bisphenol A (BPA) is a plasticizer that is used to harden plastics and polycarbonates. Phthalates are used to add flexibility to polyvinyl chloride containing plastics. The main metabolite of di(2-ethylhexyl) phthalate (DEHP) is mono(2-ethylhexyl) phthalate (MEHP) and it is even more toxic than the parent compound. Humans are usually exposed to these chemicals in mixtures by different routes starting from fetal period. However, there are not many studies in literature that investigate the combined effects of these chemicals. The aim of this study is to investigate toxic effects of BPA and/or MEHP on HepG2 cell line. We have evaluated cytotoxicity, cytomorphological, apoptotic changes, oxidative stress, oxidant/antioxidant status alterations, and endoplasmic reticulum (ER) stress. Combined exposure to BPA and MEHP caused alterations in oxidant/antioxidant status and ER stress marker proteins in both cytoplasmic and nuclear cellular fractions. We can suggest that combined exposure to EDCs may cause serious toxicological outcomes and more mechanistic studies are needed to determine the combined toxic effects.
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This study was supported by Hacettepe Research Fund Project No. TSA-2017–12882.
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GO: conceptualization, formal analysis, investigation, methodology, writing, original draft preparation, visualization, validation. PE: conceptualization, formal analysis, methodology, writing—review and editing, project co-administration. AE: formal analysis, visualization. NDZ: formal analysis, visualization. NY: formal analysis, visualization. BKG: conceptualization, methodology, writing—review and editing, project administration, data curation, supervision.
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The authors declare no competing interests. This study is the PhD thesis (Evaluation of the effects of combined exposure to endocrine disruptor chemical substances in HEPG2 cell line) of Gizem Özkemahlı (Thesis No. 499175).
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• We determined cytotoxic, oxidant and ER-stress causing effects of BPA and/or MEHP.
• BPA and/or MEHP exposure caused oxidative stress in HepG2 cells.
• Oxidative stress in by the combined exposure was higher compared to other groups.
• Combined exposure to BPA and MEHP may lead to cellular membrane damage.
• Endoplasmic reticulum stress was mainly induced in the combined exposure group.
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Ozkemahli, G., Erkekoglu, P., Ercan, A. et al. Effects of single or combined exposure to bisphenol A and mono(2-ethylhexyl)phthalate on oxidant/antioxidant status, endoplasmic reticulum stress, and apoptosis in HepG2 cell line. Environ Sci Pollut Res 30, 12189–12206 (2023). https://doi.org/10.1007/s11356-022-22937-6
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DOI: https://doi.org/10.1007/s11356-022-22937-6