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1. 1 ARTICLE Zebrafish model Since the end of the fifteenth century, the time of splendor of Paracelsus, famous physician and Swiss alchemist, humanity knows that what differentiates a poison from a remedy is determined by a very thin line: the dose. Starting from Modernity, the sciences have consolidated their knowledge and strengthened their disciplinary fields and, fortunately, today it is also known that factors such as age, nutrition and previous illnesses of the patient must also be considered when assessing the toxicity of a drug as say the laboratory zebrafish services According to the World Health Organization, toxicology can be defined as "the science that deals with the adverse health effects caused by chemical, physical or biological agents in living organisms." Of course, what is called "adverse effects" is so variable that it includes everything from stomach pain to death itself. Dr. Jimena Prieto -investigator of Conicet in the Biomembranes Laboratory- specializes in drug toxicology studies based on experiments in zebrafish -Zebrafish-, a model that it allows us to warn, a priori, what the effects would be if delivered in humans. He has focused his research on compounds to treat epilepsy and neurodegenerative diseases such as Alzheimer's. Next, tell us what your latest developments are about. -When one reviews your CV, you notice that you are a specialist in the "development of nanotechnological products in the zebrafish experimentation model". What do you mean by that? -It is related to research in a cross-sectional field: toxicology. From here, together with other members of the Laboratory, we evaluate the effects caused by the nanotechnological compounds that we design in the larvae of these animals, during their first days of life when they hatch. 2 ARTICLE Zebrafish model -What effects do they study? IBD zebrafish model -For example, if they cause their death, or if they cause changes in the morphology -that is, if it generates bad formations- of the liver, the heart and other behavioral parameters such as neurotoxicity. We perform, in this framework, various tests that allow us to notice certain results that have as horizon what could happen to humans and a therapy to a possible disease.

2. -What fish larvae work as a model to know what, in the future, could happen to humans with the supply of a drug that you design ... -Exactly, because there are certain organs that, from a cellular perspective, present structures and functions very similar to ours. Therefore, if the compound we develop is hepatotoxic in the larvae (they damage their livers), probably the same will happen in humans. -What diseases have you tried the zebrafish model for? -In epilepsy, for example. We induce the disease and then we supply the drugs to evaluate how they responded. Right now we have a line of research that also focuses on the development of treatments for Alzheimer's and other neurodegenerative diseases. In this specific case we place drugs in a transporter that acts as a delivery and transfers them directly to the brain. 3 ARTICLE - How exactly act those transporters? -They are products that we design on a nanometric scale and increase the effectiveness with which the drug reaches the brain; unlike what happens, for example, when a person takes an aspirin and disseminates throughout the body. -If the larvae are so small and the products they design have a nanometric scale, how do they investigate? -We use special plates with -nearly one hundred wells and in each one we place up to three larvae. Then, we continue the research with magnifying glasses of considerable magnification. As these organisms are transparent we can clearly observe the liver, the heart, the intestine and the circulatory system. -If drugs work effectively in larvae, how does the process continue? Zebrafish toxicity assay -We're going to try it on more complex models like mice. Then, if the results are also the expected ones, we should resort to a sufficient monetary support to promote a scaling up. It is one thing to try the drug in the laboratory and quite another to produce it on an industrial level. - So the toxicological analysis is fundamental as the first link in the design of any medicine ... -Of course. Above all, we must bear in mind that nanotechnology - employed in the field of health - is present in the most everyday objects: from tennis rackets to stockings and paintings. They even go on the market and we buy them without realizing that they could have been

3. developed without respecting the parameters of toxicity. In fact, it is so important that the previous testing we perform for our laboratory tests is also practiced in the design of products belonging to other areas. 4 ARTICLE ZeClinics is a Biotech Contract Research Organization (CRO) and early phase biopharmaceutical company (PHARMA) that uses zebrafish (Danio rerio) for the safety and efficacy analysis of new chemical molecules. It has the support of Pompeu Fabra University (UPF) that allows them to grow within the exciting environment of the Biomedicine Research Park of Barcelona (PRBB). Its commercial strengths are based on high technical expertise and top-level research facilities, combined with attractive strategic partnerships and academic collaborations. Its objective is to challenge the traditional process of drug discovery by offering a series of personalized, rapid and reliable tests to evaluate the safety and biomedical relevance of new molecules that use zebrafish. In a challenging economic environment, ZeClinics represents a good example of a business model that uses research and innovation as a way to succeed. Zebrafish model for IBD Bearing in mind that your work stimulates research on treatment and cure of diseases as present as cancer, Alzheimer's and other calamities, we are delighted to work with ZeClinics. Whenever it is necessary! 5 ARTICLE . Although initially it was alleged that glyphosate-based herbicides lacked harmful effects on animals, in recent years considerable evidence has accumulated that they can generate toxic effects in a broad spectrum of living beings, including bacteria, algae, crustaceans (Tsui & Chu, 2003; Brausch & Smith, 2007), annelids, molluscs, fish (Ojeda et al., 2007; Cavalcante et al., 2008; Carmo Langiano, & Martinez, 2008; Bortagaray et al. ., 2009), amphibians (Mann & Bidwell, 1999; Smith, 2001; Relyea, 2005; Quassinti et al., 2008; Paganelli et al., 2010), birds and mammals (Acquavella et al., 1999; Richard et al. , 2005). In humans, when glyphosate is administered in doses generally considered non-toxic, it is capable of affecting cell function, such as in steroidogenesis, cell viability of the human placenta, and blood cells. https://www.ikanbiotech.com/