Naslov
Combined toxic effects of BPA and its two analogues BPAP and BPC in a 3D HepG2 cell model

Autori
Štampar, Martina ; Ravnjak, Tin ; Domijan, Ana- Marija ; Žegura, Bojana

Kolaboracija
Bilateralni projekt, BI-HR/20-21-019

Izvornik
Molecules (1420-3049) 28 (2023); 3085, 16

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
BP analogues ; hepatic in vitro 3D cell model ; combined exposure ; viability ; oxidative stress

Sažetak
Bisphenol A (BPA) is one of the most commonly used substances in the manufacture of a variety of everyday products. Growing concerns about its hazardous properties, which include endocrine disruption and genotoxicity, have led to its gradual replacement by presumably safer analogues in the manufacturing of plastics. The widespread use of BPA and, more recently, its analogues has led to an increase in their residues in the environment, however, our knowledge of their toxicological profiles is limited and, in particular, their combined effects are unknown. In the present study, we investigated the toxic effects caused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP and BPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed that BPA did not reduce cell viability in HepG2 spheroids after 24-hour exposure. In contrast, BPAP and BPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC) decreased cell viability in a dose- dependent manner, but the significant difference was only observed for the combination of BPA/BPC (both at 40 µM). After 96-h exposure, none of the BPs studied affected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cell viability in a dose-dependent manner that was significant for the combination of 4 µM BPA and 4 µM BPAP. None of the BPs and their binary mixtures studied affected the surface area and growth of spheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggered oxidative stress, as measured by the production of reactive oxygen species and malondialdehyde, at both exposure times. Overall, the results suggest that it is important to study the effects of BPs as single compounds, but it is even more important to study the effects of combined exposures, as the combined effects may differ from those induced by single compounds.

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita, Farmacija

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