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

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

Orarat Wangpradit, Andrea Adamcakova-Dodd, Katharina Heitz, Larry Robertson, Peter S Thorne and Gregor Luthe
Environmental science and pollution research international, Vol.23(3), pp.2128-2137
02/2016
DOI: 10.1007/s11356-015-5022-5
PMCID: PMC4803647
PMID: 26400242

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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.
Kidney - drug effects Kidney - immunology Rats Male Polychlorinated Biphenyls - metabolism Rats, Sprague-Dawley Prostaglandin-Endoperoxide Synthases - immunology Macrophages, Alveolar - enzymology Animals Polychlorinated Biphenyls - chemistry Polychlorinated Biphenyls - toxicity Macrophages, Alveolar - drug effects Lung - drug effects Dendrimers - chemistry Prostaglandins - immunology Lung - metabolism Lung - immunology Macrophages, Alveolar - immunology

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