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PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats

  • PCBs: Exposures, Effects, Remediation and Regulation with special reference to PCBs in Schools
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Abstract

Polychlorinated biphenyls (PCBs) persist and accumulate in the ecosystem depending upon the degree of chlorination of the biphenyl rings. Airborne PCBs are especially susceptible to oxidative metabolism, yielding mono- and di-hydroxy metabolites. We have previously demonstrated that 4-chlorobiphenyl hydroquinones (4-CB-HQs) acted as cosubstrates for arachidonic acid metabolism by prostaglandin H synthase (PGHS) and resulted in an increase of prostaglandin production in vitro. In the present study, we tested the capability of 4-CB-HQ to act as a co-substrate for PGHS catalysis in vivo. BQ and 4-CB-2′,5′-HQ were administered intratracheally to male Sprague-Dawley rats (2.5 μmol/kg body weight) using nanosized polyamidoamine (PAMAM) dendrimers as carriers. We found that 24 h post application, PGE2 metabolites in kidney of rats treated with 4-CB-2′,5′-HQ were significantly increased compared to the controls. The increase of PGE2 metabolites was correlated with increased alveolar macrophages in lung lavage fluid. The elevation of PGE2 synthesis is of great interest since it plays a crucial role in balancing homeostasis and inflammation where a chronic disturbance may increase risk of cancer. PAMAM dentrimers proved to be an effective transport medium and did not stimulate an inflammatory response themselves.

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Acknowledgments

This publication was made possible by NIH grant P42 ES 013661 and its training core from the National Institute of Environmental Health Sciences (NIEHS), and by The University of Iowa Environmental Health Sciences Research Center, P30 ES05605, through its Pulmonary Toxicology Facility. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the granting agencies.

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Authors and Affiliations

  1. Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 100 Oakdale Campus, Iowa City, IA, 52242, USA

    Orarat Wangpradit, Larry Robertson, Peter S. Thorne & Gregor Luthe

  2. Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA

    Orarat Wangpradit, Andrea Adamcakova-Dodd, Katharina Heitz, Larry Robertson, Peter S. Thorne & Gregor Luthe

  3. Pulmonary Toxicology Facility, Environmental Health Science Research Center, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA

    Andrea Adamcakova-Dodd & Peter S. Thorne

  4. Saxion University of Applied Sciences, Institute for Life Science and Technology, Enschede, The Netherlands

    Gregor Luthe

  5. Sirindhorn College of Public Health, Bansuan, Muang, Chonburi, 20000, Thailand

    Orarat Wangpradit

  6. Luthe-Pharma, Fabrikstrasse 3, 48599, Gronau, Germany

    Gregor Luthe

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  1. Orarat Wangpradit
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  2. Andrea Adamcakova-Dodd
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Correspondence to Gregor Luthe.

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Wangpradit, O., Adamcakova-Dodd, A., Heitz, K. et al. PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats. Environ Sci Pollut Res 23, 2128–2137 (2016). https://doi.org/10.1007/s11356-015-5022-5

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