title: TCDD‑induced chick cardiotoxicity is abolished by a selective cyclooxygenase‑2 (COX‑2) inhibitor NS398.
abstract: Halogenated aromatic hydrocarbons, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are known to cause severe heart defects in avian species. However, the mechanism of TCDD-induced chick cardiovascular toxicity is unclear. In this study, we investigated cyclooxygenase-2 (COX-2) as a possible mechanism of TCDD-induced cardiotoxicity. Fertile chicken eggs were injected with TCDD and a COX-2 selective inhibitor, NS398, and we investigated chick heart failure on day 10. We found that the chick heart to body weight ratio and atrial natriuretic factor mRNA expression were increased, but this increase was abolished with treatment of NS398. In addition, the morphological abnormality of an enlarged ventricle resulting from TCDD exposure was also abolished with co-treatment of TCDD and NS398. Our results suggested that TCDD-induced chick heart defects are mediated via the nongenomic pathway and that they do not require the genomic pathway.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Fujisawa
authors.forename: Shouta M M
authors.initials: SM
authors.lastname: Nakayama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D000931:Antidotes / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D047108:Embryonic Development / Q000187:drug effects; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009578:Nitrobenzenes / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011897:Random Allocation; D013449:Sulfonamides / Q000627:therapeutic use; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000931:Antidotes; D030161:Avian Proteins; D052246:Cyclooxygenase 2 Inhibitors; D004785:Environmental Pollutants; D009578:Nitrobenzenes; D000072317:Polychlorinated Dibenzodioxins; D013449:Sulfonamides; D013723:Teratogens; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009320:Atrial Natriuretic Factor; D001189:Aryl Hydrocarbon Hydroxylases; C108015:cytochrome P-450 CYP1A5; D051546:Cyclooxygenase 2