PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats
2016
Wangpradit, Orarat | Adamcakova-Dodd, Andrea | Heitz, Katharina | Robertson, Larry | Thorne, Peter S. | Luthe, Gregor
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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