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Modulation of cell viability, oxidative stress, calcium homeostasis, and voltage- and ligand-gated ion channels as common mechanisms of action of (mixtures of) non-dioxin-like polychlorinated biphenyls and polybrominated diphenyl ethers

  • PCB mixtures in a complex world
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Abstract

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that exert neurodevelopmental and neurobehavioral effects in vivo in humans and animals. Acute in vitro neurotoxic effects include changes in cell viability, oxidative stress, and basal intracellular calcium levels. Though these acute cellular effects could partly explain the observed in vivo effects, other mechanisms, such as effects on calcium influx and neurotransmitter receptor function, likely contribute to the disturbance in neurotransmission. This concise review combines in vitro data on cell viability, oxidative stress and basal calcium levels with recent data that clearly demonstrate that (hydroxylated) PCBs and (hydroxylated) PBDEs can exert acute effects on voltage-gated Ca2+ channels as well as on excitatory and inhibitory neurotransmitter receptors in vitro. These novel mechanisms of action are shared by NDL-PCBs, OH-PBDEs, and some other persistent organic pollutants, such as tetrabromobisphenol-A, and could have profound effects on neurodevelopment, neurotransmission, and neurobehavior in vivo.

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Acknowledgments

Elsa C. Antunes Fernandes, Milou M.L. Dingemans, Hester S. Hendriks, Regina G.D.M. van Kleef, Wendy T. Langeveld, Marieke Meijer, Ad Reniers, and other members of the Neurotoxicology Research Group (IRAS) are gratefully acknowledged for their valuable scientific and technical support throughout the projects that provided the data and insight to prepare this review. I sincerely apologize to all the authors of primary literature or previous reviews that could not be included due to space limitations. This study was supported by the European Union [ATHON: FP7-FOOD-CT-2005-022923; ENFIRO: FP7-ENV-2008-1-226563; DENAMIC: grant no. FP7-ENV-2011-282957] and the Faculty of Veterinary Medicine of Utrecht University.

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  1. Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, 3508 TD, Utrecht, The Netherlands

    Remco H. S. Westerink

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  1. Remco H. S. Westerink
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Correspondence to Remco H. S. Westerink.

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Responsible editor: Henner Hollert

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Westerink, R.H.S. Modulation of cell viability, oxidative stress, calcium homeostasis, and voltage- and ligand-gated ion channels as common mechanisms of action of (mixtures of) non-dioxin-like polychlorinated biphenyls and polybrominated diphenyl ethers. Environ Sci Pollut Res 21, 6373–6383 (2014). https://doi.org/10.1007/s11356-013-1759-x

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  • DOI: https://doi.org/10.1007/s11356-013-1759-x

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