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TCDD-induced chick cardiotoxicity is abolished by a selective cyclooxygenase-2 (COX-2) inhibitor NS398

  • Organ Toxicity and Mechanisms
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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.

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References

  • Abell TJ, Richards AM, Ikram H, Espiner EA, Yandle T (1989) Atrial natriuretic factor inhibits proliferation of vascular smooth muscle cells stimulated by platelet-derived growth factor. Biochem Biophys Res Commun 160:1392–1396

    Article  CAS  PubMed  Google Scholar 

  • Antkiewicz DS, Burns CG, Carney SA, Peterson RE, Heideman W (2005) Heart malformation is and early response to TCDD in embryonic zebrafish. Toxicol Sci 84:368–377

    Article  CAS  PubMed  Google Scholar 

  • Bird DM, Tucker PH, Fox GA, Laguë PC (1983) Synergistic effects of aroclor 1254 and mirex on the semen characteristics of American Kestrels. Arch Environ Contam Toxicol 12:633–640

    Article  CAS  PubMed  Google Scholar 

  • Blankenship AL, Hilscherova K, Nie M, Coady KK, Villalabos SA, Kannan K, Powell DC, Bursian SJ, Giesy JP (2003) Mechanisms of TCDD-induced abnormalities and embryo lethality in white leghorn chickens. Comp Biochem Physiol C 136:47–62

    Article  CAS  Google Scholar 

  • Cameron VA, Ellmers LJ (2003) Minireview: natriuretic peptides during development of the fetal heart and circulation. Endocrinology 144:2191–2194

    Article  CAS  PubMed  Google Scholar 

  • Cameron VA, Rademaker M, Ellmers LJ, Espiner E, Nicholls M, Richards A (2000) Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct. Endocrinology 141:4690–4697

    CAS  PubMed  Google Scholar 

  • Carney SA, Peterson RE, Heideman W (2004) 2,3,7,8-Tetrachlorodibenzo-p-dioxin activation of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a CYP1A-independent mechanism in zebrafish. Mol Pharmacol 66:512–521

    CAS  PubMed  Google Scholar 

  • Chan W, Yao G, Gu YZ, Bradfield C (1999) Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. Demonstration of competition and compensation. J Biol Chem 274:12115–12123

    Article  CAS  PubMed  Google Scholar 

  • De Mello WC, Danser AH (2000) Angiotensin II and the heart: on the intracrine renin–angiotensin system. Hypertension 35:1183–1188

    Article  PubMed  Google Scholar 

  • Degner SC, Kemp MQ, Hockings JK, Romagnolo DF (2007) Cyclooxygenase-2 promoter activation by the aromatic hydrocarbon receptor in breast cancer MCF-7 cells: repressive effects of conjugated linoleic acid. Nutr Cancer 59:248–257

    Article  CAS  PubMed  Google Scholar 

  • Degner SC, Papoutsis AJ, Selmin O, Romagnolo DF (2009) Targeting of aryl hydrocarbon receptor-mediated activation of cyclooxygenase-2 expression by the indole-3-carbinol metabolite 3,3′-diindolylmethane in breast cancer cells. J Nutr 139:26–32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dong B, Matsumura F (2009) The conversion of rapid TCCD nongenomic signals to persistent inflammatory effects via select protein kinases in MCF10A cells. Mol Endocrinol 23:549–558

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dong B, Matsumura F, Kullman SW (2010a) TCDD induced pericardial edema and relative COX-2 expression in medaka (Oryzias Latipes) embryos. Toxicol Sci 118:213–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dong B, Nishimura N, Vogel CF, Tohyama C, Matsumura F (2010b) TCDD-induced cyclooxygenase-2 expression is mediated by the nongenomic pathway in mouse MMDD1 macula densa cells and kidneys. Biochem Pharmacol 79:487–497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dorn GW II, Robbins J, Sugden PH (2003) Phenotyping hypertrophy: eschew obfuscation. Circ Res 92:1171–1175

    Article  CAS  PubMed  Google Scholar 

  • Fletcher N, Hanberg A, Hakansson H (2001) Hepatic vitamin A depletion is a sensitive marker of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in four rodent species. Toxicol Sci 62:166–175

    Article  CAS  PubMed  Google Scholar 

  • Futaki N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S (1994) NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins 47:55–59

    Article  CAS  PubMed  Google Scholar 

  • Gradin K, McGuire J, Wenger R, Kvietikova I, Whitelaw M, Toftgard R, Tora L, Gassman M, Poellinger L (1996) Functional interference between hypoxia and dioxin signal transduction pathways: competition for recruitment of the ARNT transcription factor. Mol Cell Biol 16:5221–5231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Head JA, Kennedy SW (2010) Correlation between an in vitro and an in vivo measure of dioxin sensitivity in birds. Ecotoxicology 19:377–382

    Article  CAS  PubMed  Google Scholar 

  • Heid SE, Walker MK, Swanson HI (2001) Correlation of cardiotoxicity mediated by halogenated aromatic hydrocarbons to aryl hydrocarbon receptor activation. Toxicol Sci 61:187–196

    Article  CAS  PubMed  Google Scholar 

  • Higginbotham GR, Huang A, Firestone D, Verrett J, Ress J, Campbell AD (1968) Chemical and toxicological evaluations of isolated and synthetic chloro derivatives of dibenzo-p-dioxin. Nature 220:702–723

    Article  CAS  PubMed  Google Scholar 

  • Iijima K, Geshi E, Nomizo A, Arata Y, Katagiri T (1998) Alterations in sarcoplasmic reticulum and angiotensin II type 1 receptor gene expression after myocardial infarction in rats. Jpn Circ J 62:449–454

    Article  CAS  PubMed  Google Scholar 

  • Ivnitski I, Elmaoued R, Walker MK (2001) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibition of coronary development is preceded by a decrease in myocyte proliferation and an increases in cardiac apoptosis. Teratology 64:201–212

    Article  CAS  PubMed  Google Scholar 

  • Ivnitski-Steele ID, Walker MK (2003) Vascular endothelial growth factor rescues 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibition of coronary vasculogenesis. Birth Defects Res A 67:496–503

    Article  CAS  Google Scholar 

  • Jones SP, Kennedy SW (2009) Chicken embryo cardiomyocyte cultures: a new approach for studying effects of halogenated aromatic hydrocarbons in the avian heart. Toxicol Sci 109:66–74

    Article  CAS  PubMed  Google Scholar 

  • Kawakami H, Okayama H, Hamada M, Hiwada K (1996) Alteration of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats. Clin Sci 90:197–204

    CAS  PubMed  Google Scholar 

  • Kopf PG, Walker MK (2009) Overview of developmental heart defects by dioxins, PCBs, and pesticides. J Environ Sci Health C 27:276–285

    Article  CAS  Google Scholar 

  • Larson JM, Karasov WH, Sileo L, Stromborg KL, Hanbidge BA, Giesy JP, Jones PD, Tillitt DE, Verbrugge DA (1995) Reproductive success, developmental anomalies, and environmental contaminants in double-crested cormorants (Phalacrocorax auritus). Environ Toxicol Chem 5(4):553–559

    Google Scholar 

  • Li W, Matsumura F (2008) Significance of the nongenomic, inflammatory pathway in mediating the toxic action of TCDD to induce rapid and long-term cellular responses in 3T3-L1 adipocytes. Biochem 47:13997–14008

    Article  CAS  Google Scholar 

  • Li W, Vogel CF, Wu D, Matsumura F (2010) Non-genomic action of TCDD to induce inflammatory responses in HepG2 human hepatoma cells and in liver of C57BL/6J mice. Biol Chem 391:1205–1219

    Article  CAS  PubMed  Google Scholar 

  • Matsumura F (2009) The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects. Biochem Pharmacol 77:608–626

    Article  CAS  PubMed  Google Scholar 

  • Mazzolai L, Nussberger J, Aubert J, Brunner D, Brunner H, Pedrazzini T (1998) Blood pressure independent cardiac hypertrophy induced by locally activated renin–angiotensin system. Hypertension 31:1324–1330

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin J Jr, Marliac JP, Verrett MJ, Mutchler MK, Fitzhugh OG (1963) The injection of chemicals into the yolk sac of fertile eggs prior to incubation as a toxicity test. Toxicol Appl Pharmacol 5:760–771

    Article  CAS  PubMed  Google Scholar 

  • Ohtake F, Takeyama K, Matsumoto T, Kitagawa H, Yamamoto Y, Nohara K, Tohyama C, Krust A, Mimuea J, Chambon P, Yanagisawa J, Fujii-Kuriyama Y, Kato S (2003) Modulation of oestrogen receptor signaling by association with the activated dioxin receptor. Nature 423:545–550

    Article  CAS  PubMed  Google Scholar 

  • Passier RC, Smits JF, Verluyten MJ, Studer R, Drexler H, Daemen MJ (1995) Activation of angiotensin-converting enzyme expression in infarct zone following myocardial infarction. Am J Physiol 269(4):H1268–H1276

    CAS  PubMed  Google Scholar 

  • Peden-Adams M, Alonso K, Godard C, Skipper W, Mashburn W, Hoover J, Charbonneau C, Henshel D, Dickerson R (1998) Effects of environmentally relevant concentrations of 2,3,7,8-TCDD on domestic chicken immune function and CYP450 activity: F1 generation and egg injection studies. Chemosphere 37:1923–1939

    Article  CAS  PubMed  Google Scholar 

  • Perrella M, Schwab T, O’Murchu B, Redfield M, Wei C, Edwards B, Burnett J (1992) Cardiac atrial natriuretic factor during evolution of congestive heart failure. Am J Physiol 262:1248–1255

    Google Scholar 

  • Pieruzzi F, Abassi ZA, Keiser HR (1995) Expression of renin–angiotensin system components in the heart, kidneys, and lungs of rats with experimental heart failure. Circulation 92:3105–3112

    Article  CAS  PubMed  Google Scholar 

  • Roman RJ, Renic M, Dunn KM, Takeuchi K, Hacein-Bey L (2006) Evidence that 20-HETE contributes to the development of acute and delayed cerebral vasospasm. Neurol Res 28:738–749

    Article  CAS  PubMed  Google Scholar 

  • Sadoshima J, Izumo S (1993a) Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73:413–423

    Article  CAS  PubMed  Google Scholar 

  • Sadoshima J, Izumo S (1993b) Signal transduction pathways of angiotensin II-induced c-fos gene expression in cardiac myocytes in vitro. Roles of phospholipid-derived second messengers. Circ Res 73:424–438

    Article  CAS  PubMed  Google Scholar 

  • Schmittle SC, Edward HM, Morris D (1958) A disorder of chickens probably due to a toxic feed: preliminary report. J Am Vet Med Assoc 132:216–219

    CAS  PubMed  Google Scholar 

  • Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH (1990) Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest 86:1913–1920

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sommer RJ, Hume AJ, Ciak JM, Vannostrand JJ, Friggens M, Walker MK (2005) Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor. Toxicol Sci 83:363–371

    Article  CAS  PubMed  Google Scholar 

  • Teraoka H, Kubota A, Kawai Y, Hiraga T (2008) Prostanoid signaling mediates circulation failure caused by TCDD in developing zebrafish. Interdiscip Stud Environ Chem 1:61–80

    Google Scholar 

  • Thackaberry EA, Nunez BA, Ivnitski-Steele ID, Friggins M, Walker MK (2005) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on murine heart development: alteration in fetal and postnatal cardiac growth, and postnatal cardiac chronotropy. Toxicol Sci 88:242–249

    Article  CAS  PubMed  Google Scholar 

  • Toraason M, Wey H, Woolery M, Plews P, Hoffmann P (1995) Arachidonic acid supplementation enhances hydrogen peroxide induced oxidative injury of neonatal rat cardiac myocytes. Cardiovasc Res 29:624–628

    Article  CAS  PubMed  Google Scholar 

  • Uno S, Dalton TP, Sinclair PR, Gorman N, Wang B, Smith AG, Millar ML, Shertzer HG, Nebert DW (2004) CYP1a1 (−/−) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria. Toxicol Appl Pharmcol 196:410–421

    Article  CAS  Google Scholar 

  • Walker MK, Catron TF (2000) Characterization of cardiotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related chemicals during early chick embryo development. Toxicol Appl Pharmacol 167:210–221

    Article  CAS  PubMed  Google Scholar 

  • Walker MK, Pollenz RS, Smith SN (1997) Expression of the Aryl hydrocarbon receptor (AhR) and AhR nuclear translator during chick cardiogenesis is consistent with 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced heart defects. Toxicol Appl Pharmacol 143:407–419

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Bishopric N, Pratt R (1997) Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. J Biol Chem 272:14860–14866

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, which was awarded to M. Ishizuka (No. 24248056). We express our sincere thanks to Dr. F. Mastsumura for his kind suggestions on our study.

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The authors declare that they have no conflict of interest.

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Correspondence to Mayumi Ishizuka.

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Fujisawa, N., Nakayama, S.M.M., Ikenaka, Y. et al. TCDD-induced chick cardiotoxicity is abolished by a selective cyclooxygenase-2 (COX-2) inhibitor NS398. Arch Toxicol 88, 1739–1748 (2014). https://doi.org/10.1007/s00204-014-1225-7

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