ZEBRAFISH EMBRYOS AS TOXICOLOGICAL MODELSZF: ZebraFish ModelElisabet Teixidó                                              ...
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Zebrafish Model (E. Teixidó)

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Transcript of "Zebrafish Model (E. Teixidó)"

  1. 1. ZEBRAFISH EMBRYOS AS TOXICOLOGICAL MODELSZF: ZebraFish ModelElisabet Teixidó • Small sizeInvestigadora CERETOX • Short generation time (3-4 months)elisabet.teixido@gmail.com • Large number of offspring • Ex utero development • Rapid embryonic development JORNADA TOX® • • Transparency of the embryos Embryonic stages (≤ 5 dpf) are not regulated 1 de Febrero de 2013 • Evolutionary well-conserved human drug targets Parc Científic de Barcelona ZEBRAFISH EMBRYO TOXICITY TEST DEVELOPMENTAL TOXICOLOGY Classification as teratogen (+/-) TI ZFET Mammals humans (LC50/EC50) TI>1.5 Lethal and Valproic acid 3.3 + + + CRANIOFACIAL ALTERATIONS teratogenic + + ? endpoints Caffeine 6.2 CONTROL Embryo exposure All-trans retinoic acid 26.8 + + + Egg collection Control of fertilization 26º C success 14 h/10 h ligth/dark Methoxyacetic acid 2.9 + + ? ETHANOL 1% Salicylic sodium salt 3.2 + + - Hydroxyurea 1.3 - + ? What’s the difference? Boric acid 2.9 + + + Paraoxon-methyl 8.8 + - ? D-(+)-glucose / - - - Ascorbic acid / - - - Overall concordance 80%! SAFETY PHARMACOLOGY: CARDIOTOXICITY ASSAY WHAT CAN PROVIDE THE ZEBRAFISH MODEL? Heartbeat regularity: QT prolonging drugs VENTRICLE - ATRIUM Intermediate step between cell-based test and mammalian test VENTRICULAR AND ATRIAL RATE CONTROL VENTRICULAR RATE 250 Screening of chemical libraries Heart rate (beats/min) 200 Ventricle Atrium 150 Used as tool to group and prioritize chemicals 100 Reduce the number of mammals used in experimental toxicology 50 TERFENADINE 0 Control Terfenadine Isoprenaline Potential to provide a level of predictivity as good or better than current 10µM 1mM models Stroke volume (pL) Cardiac output (pL/sec) Control 239.7 ± 13.3 659.7 ± 26.6 Excellent model to study drug-induced cardiac irregularities such as QT Terfenadine 10 µM 298.0 ± 18.1 346.9 ± 21.9 Isoprenaline 1 mM 326.5 ± 34.7 1108.7 ± 112.8 prolongation 1

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