Comparative in silico and in vitro evaluation of possible toxic effects of bisphenol derivatives in HepG2 cells

Author:

Balci-Ozyurt Aylin123,Yirun Anıl145,Cakır Deniz Arca167,Ozcelik İbrahim189,Bacanli Merve1011,Ozkemahli Gizem89,Sabuncuoglu Suna1,Basaran Nursen1,Erkekoglu Pınar1ORCID

Affiliation:

1. Hacettepe University , Faculty of Pharmacy, Department of Toxicology, Ankara , Turkey

2. School of Pharmacy , Department of Toxicology, , Istanbul , Turkey

3. Bahçeşehir University , Department of Toxicology, , Istanbul , Turkey

4. Faculty of Pharmacy , Department of Toxicology, , Adana , Turkey

5. Çukurova University , Department of Toxicology, , Adana , Turkey

6. Hacettepe Vaccine Institute , Department of Vaccine Technology, , Ankara , Turkey

7. Hacettepe University , Department of Vaccine Technology, , Ankara , Turkey

8. Faculty of Pharmacy , Department of Toxicology, , Erzincan , Turkey

9. Erzincan Binali Yildirim University , Department of Toxicology, , Erzincan , Turkey

10. Faculty of Pharmacy , Department of Toxicology, , Ankara , Turkey

11. Health Sciences University , Department of Toxicology, , Ankara , Turkey

Abstract

Abstract Introduction Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and “low dose toxicity”. With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased. Methods In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects. Conclusion Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.

Funder

Hacettepe University Scientific Research Unit Research Project

Publisher

Oxford University Press (OUP)

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