Toxicology Letters

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