Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

Abstract

The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish.

• Authors: Hiroki Teraoka, Yuki Okuno, Daisuke Nijoukubo, Ayumi Yamakoshi, Richard E Peterson, John J Stegeman, Takio Kitazawa, Takeo Hiraga, Akira Kubota
• Journal: Aquatic toxicology (Amsterdam, Netherlands) (Aquat Toxicol) Vol. 154 Pg. 19-26 (Sep 2014) ISSN: 1879-1514 [Electronic] Netherlands
• PMID: 24858302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• AHR2 protein, zebrafish
• Antioxidants
• Cyclooxygenase 2 Inhibitors
• Polychlorinated Dibenzodioxins
• Receptors, Aryl Hydrocarbon
• Thromboxanes
• Water Pollutants, Chemical
• Zebrafish Proteins
• arnt protein, zebrafish
• Aryl Hydrocarbon Receptor Nuclear Translocator
• Cyclooxygenase 2
• Ascorbic Acid

Topics

• Animals
• Antioxidants (pharmacology)
• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics, metabolism)
• Ascorbic Acid (pharmacology)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Edema, Cardiac (chemically induced, enzymology, physiopathology)
• Embryo, Nonmammalian (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Knockdown Techniques
• Polychlorinated Dibenzodioxins
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Signal Transduction (drug effects)
• Thromboxanes (metabolism)
• Water Pollutants, Chemical (toxicity)
• Zebrafish (growth & development)
• Zebrafish Proteins (genetics, metabolism)