Zebrafish as an alternative animal model in human and animal vaccination research

Much of medical research relies on animal models to deepen knowledge of the causes of animal and human diseases, as well as to enable the development of innovative therapies. Despite rodents being the most widely used research model worldwide, in recent decades, the use of the zebrafish (Danio rerio) model has exponentially been adopted among the scientific community. This is because such a small tropical freshwater teleost fish has crucial genetic, anatomical and physiological homology with mammals. Therefore, zebrafish constitutes an excellent experimental model for behavioral, genetic and toxicological studies which unravels the mechanism of various human diseases. Furthermore, it serves well to test new therapeutic agents, such as the safety of new vaccines. The aim of this review was to provide a systematic literature review on the most recent studies carried out on the topic. It presents numerous advantages of this type of animal model in tests of efficacy and safety of both animal and human vaccines, thus highlighting gains in time and cost reduction of research and analyzes

Zebrafish as an animal model for food safety research: trends in the animal research

Toxicity studies in mammals continue to be the most appropriate model for predicting risk in 5 humans, but they tend to be expensive and time-consuming. In the aftermath of the genetic 6 sequencing of zebrafish (Danio rerio), that species showed to be highly genetically homologous 7 to humans. The use of the zebrafish model to assess food toxicity is already a reality as it is 8 capable of biological processes difficult to reproduce in vitro. Studies of complex mechanisms 9 of absorption, distribution, metabolism and excretion as well as cellular and tissue interactions 10 are of great information value resulting in time, space and cost savings, when compared to 11 studies with rodents. This review addresses the relevance of zebrafish model in food safety 12 research, both in the use of ingredients and innocuous food additives as well as for establishing 13 levels of safe food contaminant residues present in the environment. Toxicological screening 14 using the zebrafish model integrate the evaluation of teratogenicity, cardiotoxicity, 15 hepatotoxicity, genotoxicity, neurotoxicity, endocrinetoxicity, reproductive and behavioral 16 aspects. These are important endpoints for food safety assessment, which take substantially less 17 time than in mammalian tests. Furthermore, it serves well as a screening test follow-up for 18 validating favorable results in murine models, hence accelerating the risk assessment process 19 of products submitted for approval and registration, prioritizing safe compounds and reducing 20 unnecessary costs in subsequent mammalian studies. In conclusion, zebrafish model can be a 21 useful tool for food safety tests, however, additional studies are needed to further validate this 22 model for registration of new food ingredients and additives

Zebrafish toxicological screening could aid Leishmaniosis drug discovery

Background Recently a screen from a library of 1.8 million compounds identified in vitro a potent activity of the 2-aminobenzimidazoles series against Leishmania infantum, the etiological agent responsible by over 20.000 deaths each year. Several analogs were synthesized and in vitro tested through an optimization program, leading to a promising 2-aminobenzimidazoles derived compound (2amnbzl-d) that was progressed to in vivo mice studies. However, the not expected toxic effects prevented its progression to more advanced preclinical and clinical phases of drug development. Due to limitations of cell models in detecting whole organism complex interactions, 90% of the compounds submitted to pre-clinical tests are reproved. The use of Zebrafish embryo models could improve this rate, saving mammals, time and costs in the development of new drugs. To test this hypothesis, we compared 2amnbzl-d with two compounds with already established safety profile: carbamazepine and benznidazole, using an embryo Zebrafish platform based on acute toxicity, hepatotoxicity, neurotoxicity and cardiotoxicity assays (Pltf-AcHpNrCd). Results Tests were performed blindly, and the results demonstrated the presence of lethal and teratogenic effects (CL50%: 14.8 µM; EC50%: 8.6 µM), hepatotoxic in concentrations above 7.5 µM and neurotoxic in embryos exposed to 15 µM of 2amnbzl-d. Nevertheless, benznidazole exposition showed no toxicity and only the 100 µM of carbamazepine induced a bradycardia. Conclusions Results using Pltf-AcHpNrCd with zebrafish reproduced that found in the toxicological tests with mammals to a portion of the costs and time of experimentation