Toxicology Letters

J.B. Legradi, P.H. Cenijn, R.P. Carvalho, A. K. Dahlberg, L Asplund, Ake Bergman, J. Legler

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Abstract

Disruption of mitochondrial oxidative phosphorylation
(OXPHOS) is amechanism of toxicity which disturbs mitochondrial
respiration and thereby alters the energy metabolism [1]. This may
lead to severe health effects, such as reproductive insufficiency
and wasting syndrome [2]. Disruption of OXPHOS is generally
studied in vitro using isolated mitochondrial membranes or in
whole organisms using tissue extracts [3]. The goal of this study
was to develop a method to measure OXPHOS disruption in vivo
in a living organism. For this purpose we used zebrafish embryos.
We established a method of monitoring mitochondrial respiration
using a combination of three in vivo measurements: total oxygen
consumption, lactate acid production and mitochondrial membrane
potential in zebrafish during early development (0–7 days).
We studied the effects of short term and long term exposures
to model OXPHOS disruptors like FCCP (Carbonyl cyanide-ptrifluoromethoxyphenylhydrazone),
KCN (potassium cyanide)
and DNP (2,4-dinitrophenol). We also monitored dose–response
relationships over time and compared our results with a standard
in vitro method. Our results indicate that disruption of OXPHOS
can be measured in vivo in the zebrafish embryo. Exposure to
model compounds showed clear differences between uncouplers
and inhibitors, as well as differences in sensitivity to OXPHOS
disruption during development. The relative potency of the used
compounds was similar between the in vivo and in vitro measurements.
Changes in the mitochondrial respiration were also seen
after a chronic exposure with a relatively low dose of disruptor.
Original languageEnglish
Title of host publicationVolume 211, Supplement, 17
PagesS118-S118
Publication statusPublished - 2012
EventEurotox 2011 -
Duration: 1 Jan 20121 Jan 2012

Conference

ConferenceEurotox 2011
Period1/01/121/01/12

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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)