title: Protective effect of prostacyclin against pre-cardiac edema caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin and a thromboxane receptor agonist in developing zebrafish.
abstract: The role of prostaglandin pathways has been suggested in some toxicological responses to dioxins. Cyclooxygenase type 2b (COX2b), thromboxane synthase, and the thromboxane receptor (TP) pathway have been implicated in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced pre-cardiac edema in developing zebrafish at 55 h post fertilization (hpf). Pre-cardiac edema refers to edema located in a small cavity between the heart and body wall of zebrafish eleutheroembryos. In the present study, we assessed the role of prostacyclin, which counteracts some biological effects of thromboxane, in TCDD-induced pre-cardiac edema. Pre-cardiac edema induced by TCDD exposure (0.5 and 1 ppb) beginning at 24 hpf was markedly inhibited by exposure to beraprost (5 and 10 μM), a prostacyclin receptor (IP) agonist, beginning at 33 hpf. The preventive effect of beraprost was reduced by exposure to CAY10441 (10 μM), an IP antagonist starting at 33 hpf. Knockdowns of the IP receptor (IP-KD) with two different morpholinos caused edema by themselves and enhanced pre-cardiac edema caused by the low concentration of TCDD (0.5 ppb). On the other hand, short exposure beginning at 48 hpf to U46619 (7.5-30 μM), a thromboxane receptor agonist caused pre-cardiac edema, which was inhibited by exposure beginning at 48 hpf to both ICI-192,605 (24 μM), a TP antagonist, and beraprost. Expression of prostacyclin synthase was increased from fertilization, plateaued by 48 hpf, and was maintained until at least 96 hpf. Overall, the results demonstrate a preventive effect of prostacyclin on TCDD-induced pre-cardiac edema in developing zebrafish.
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nijoukubo
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan; Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Yin
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Takio
authors.initials: T
authors.lastname: Kitazawa
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
authors.affiliation: Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kubota
authors.affiliation: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan. Electronic address: hteraoka@rakuno.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Teraoka
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D004489:Edema, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D017482:Receptors, Thromboxane / Q000819:agonists*; D015027:Zebrafish / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D004785:Environmental Pollutants; D010975:Platelet Aggregation Inhibitors; D000072317:Polychlorinated Dibenzodioxins; D017482:Receptors, Thromboxane; D029961:Zebrafish Proteins; C048081:beraprost; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase
keywords: Cardiovascular toxicity; Prostacyclin; TCDD; Thromboxane; Zebrafish