title: PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats.
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.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 100 Oakdale Campus, Iowa City, IA, 52242, USA.|Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.|Sirindhorn College of Public Health, Bansuan, Muang, Chonburi, 20000, Thailand.
authors.forename: Orarat
authors.initials: O
authors.lastname: Wangpradit
authors.affiliation: Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.|Pulmonary Toxicology Facility, Environmental Health Science Research Center, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamcakova-Dodd
authors.affiliation: Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Heitz
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 100 Oakdale Campus, Iowa City, IA, 52242, USA.|Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Robertson
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 100 Oakdale Campus, Iowa City, IA, 52242, USA.|Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.|Pulmonary Toxicology Facility, Environmental Health Science Research Center, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 100 Oakdale Campus, Iowa City, IA, 52242, USA. g.luthe@luthe-pharma.com.|Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA. g.luthe@luthe-pharma.com.|Saxion University of Applied Sciences, Institute for Life Science and Technology, Enschede, The Netherlands. g.luthe@luthe-pharma.com.|Luthe-Pharma, Fabrikstrasse 3, 48599, Gronau, Germany. g.luthe@luthe-pharma.com.
authors.forename: Gregor
authors.initials: G
authors.lastname: Luthe
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008297:Male; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology; D011453:Prostaglandins / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D011453:Prostaglandins; D011078:Polychlorinated Biphenyls; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Inflammatory response; PAMAM dendrimers; Polychlorinated biphenyls (PCBs); Prostaglandin E2 (PGE2); Prostaglandin H synthase (PGHS)