Abstract
Polychlorinated biphenyls (PCBs) can induce chronic oxidative stress, inflammation, and cell death, leading to coronary heart disease, endothelial dysfunction, neurotoxicity, cancer, obesity, type 2 diabetes, reproductive dysfunction, etc. The aim of this study was to investigate possible protective effect of resveratrol (2.5–20 μM) in ovarian cells exposed to PCBs. An emphasis was on identifying mechanisms of resveratrol action upon distinct structure of the individual PCB congener—planar dioxin-like PCB 77 and non-planar di-ortho-substituted PCB 153. Multiple toxicity endpoint analysis was performed. Cell viability/proliferation was assessed by Trypan Blue exclusion method, Neutral Red, Kenacid Blue, and MTT bioassays. The level of oxidative stress was measured by fluorescent probes, and flow cytometry was applied to evaluate the mode of cell death. Resveratrol applied alone did not affect cell proliferation and viability in doses up to 20 µM, although significant antioxidative activity was observed. Toxic effects of ortho-PCB 153 (cytotoxicity, oxidative stress, and cell death) were mitigated by resveratrol. On the contrary pre-incubation with resveratrol did not result in cell viability protection when planar PCB 77 was applied. This indicates that resveratrol efficacy may be linked to specific structure of the individual congener, suggesting nutritional modulation of environmental insults caused by ortho-PCBs. We point out the importance of resveratrol dosage considering that synergistic cytotoxic effect with both PCB congeners is observed at concentrations ≥ 10 μM.
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The authors gratefully acknowledge financial support provided by Croatian Science Foundation under the project IP-2020–02-9162 and University of Zagreb grant No. 0000 7000 2425.
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Marina Miletić: visualization, investigation, and data curation. Ivana Kmetič: resources, funding acquisition, conceptualization, methodology, and writing—original draft. Veronika Kovač: writing—review and editing. Branimir Šimić: supervision. Tea Petković: investigation. Dubravka Švob Štrac: methodology. Jelka Pleadin: validation. Teuta Murati: conceptualization, formal analysis, validation, and data curation. All authors read and approved the final manuscript.
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Miletić, M., Kmetič, I., Kovač, V. et al. Resveratrol ameliorates ortho- polychlorinated biphenyls’ induced toxicity in ovary cells. Environ Sci Pollut Res 30, 77318–77327 (2023). https://doi.org/10.1007/s11356-023-27812-6
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DOI: https://doi.org/10.1007/s11356-023-27812-6