3 Minute 3Rs June 2019 3 Minute 3Rs

The June episode of 3-Minute 3Rs from the North American 3Rs Collaborative (www.na3rsc.org), the NC3Rs (www.nc3rs.org.uk), and Lab Animal (www.nature.com/laban)Papers; 1. https://bit.ly/2UH4hZt2. https://go.nature.com/2W5CIea3. https://bit.ly/2Fi4td4[LA] On the road to the clinic, immunocompromised mice transplanted with patient-derived xenografts have been a frequent step for testing a drug’s efficacy and safety. However, there may soon be fisher options afoot that might help replace some of those mice. Writing in the June issue of the journal Cell, David Langenau and colleagues describe an adult zebrafish xenograft model, into which they successfully engrafted several different solid pediatric tumors. Larval versions had existed before, but an adult model offers a few notable advantages. Bigger fish can bear a larger tumor burden for a longer period of time than the small fry. Adults can be orally gavaged, meaning researchers can know exactly how much of a drug they are getting. And with acclimation, they can handle the heat – the Langenau lab kept them at 37 degrees Celsius, the same temperature a tumor will find in the human body. In the paper, the zebrafish model performed comparably to a murine one. As such, xenografted zebrafish might be valid alternatives to mice, at least at the early stages of drug testing. [NA3RsC] What if it were possible to screen for compounds with cardiotoxic side effects in less than a few hours? Dr. Farraj and colleagues from the National Health and Environmental Effects Research Laboratory explore the possibility of using zebrafish embryos to accurately predict cardiotoxicity quickly. In their publication in Scientific Reports, Farraj and colleagues describe a multi-well platform with the ability to automatically quantify the heart rate of multiple zebrafish embryos per imaging field using an algorithm they call FisHRateZ. To demonstrate the utility of this approach, embryos were exposed to compounds known to either increase or decrease the heart rate. FisHRateZ accurately detected expected changes in heart rate with high sensitivity. The whole process is also quite fast. The assessment of a full 96-well plate can be conducted in less than 50 minutes. One limitation, they note, is the inability of FisHRateZ to measure arrhythmias. Check out this paper to learn more about the platform and download the free video processing algorithms.[NC3Rs] Scientists often use indirect measures such as changes in behavior or physiology to assess whether the welfare of the animal has been compromised, but methods which have been applied to larger non-aquatic animals are often not appropriate for fish. Recently, a mathematical method has come to the rescue, allowing the amount a fish moves to be used as a marker for welfare. Dr Anthony Deakin and team at the University of Liverpool developed the method, which used cameras to track the movement of individually housed zebrafish before and after undergoing potentially painful procedures. The trajectories created by the movement of the fish were analysed using the fractal dimension technique, which is a method used to reduce the complexity of data and produce a simple scale on which to compare the adversity of different procedures. This revealed significant reductions in movement complexity in procedural groups in comparison to the control. In particular, fin-clipped and PIT-tagged groups showed reduced movement complexity, highlighting the likelihood that these routine procedures are indeed painful. The addition of lidocaine reduced the impact of the fin clipping, demonstrating that this analgesia is an advantageous refinement in fish. Follow the link in the description to find out more about this non-invasive tool to monitor zebrafish welfare.
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