Toxicology Letters
| Autor: | Jessica Legradi, Cenijn, P. H., Carvalho, R. P., Dahlberg, A. K., Asplund, L., Ake Bergman, Legler, J. |
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| Přispěvatelé: | Chemistry and Biology, Amsterdam Global Change Institute |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Volume 211, Supplement, 17, S118-S118 STARTPAGE=S118;ENDPAGE=S118;TITLE=Volume 211, Supplement, 17 Legradi, J B, Cenijn, P H, Carvalho, R P, Dahlberg, A K, Asplund, L, Bergman, A & Legler, J 2012, Toxicology Letters . in Volume 211, Supplement, 17 . pp. S118-S118, Eurotox 2011, 1/01/12 . Vrije Universiteit Amsterdam |
| Popis: | Disruption of mitochondrial oxidative phosphorylation(OXPHOS) is amechanism of toxicity which disturbs mitochondrialrespiration and thereby alters the energy metabolism [1]. This maylead to severe health effects, such as reproductive insufficiencyand wasting syndrome [2]. Disruption of OXPHOS is generallystudied in vitro using isolated mitochondrial membranes or inwhole organisms using tissue extracts [3]. The goal of this studywas to develop a method to measure OXPHOS disruption in vivoin a living organism. For this purpose we used zebrafish embryos.We established a method of monitoring mitochondrial respirationusing a combination of three in vivo measurements: total oxygenconsumption, lactate acid production and mitochondrial membranepotential in zebrafish during early development (0–7 days).We studied the effects of short term and long term exposuresto model OXPHOS disruptors like FCCP (Carbonyl cyanide-ptrifluoromethoxyphenylhydrazone),KCN (potassium cyanide)and DNP (2,4-dinitrophenol). We also monitored dose–responserelationships over time and compared our results with a standardin vitro method. Our results indicate that disruption of OXPHOScan be measured in vivo in the zebrafish embryo. Exposure tomodel compounds showed clear differences between uncouplersand inhibitors, as well as differences in sensitivity to OXPHOSdisruption during development. The relative potency of the usedcompounds was similar between the in vivo and in vitro measurements.Changes in the mitochondrial respiration were also seenafter a chronic exposure with a relatively low dose of disruptor. |
| Databáze: | OpenAIRE |
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