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.

This study evaluated the acute toxicity of sediment in a eutrophic reservoir after remediation with a calcium nitrate solution to retain phosphorus. The study involved microcosms of surface sediments and water from the sedimentwater interface in the Ibirité reservoir. This reservoir, located in the vicinity of metropolitan Belo Horizonte (Minas Gerais, SE Brazil), is a water body that receives treated effluents from an oil refinery (REGAP-Petrobras), as well as high loads of untreated urban effluents from the city of Ibirité and surrounding areas and industrial effluents from a major industrial park. Incubation times of the treatment experiments were: t = 0, t = 5, t = 10, t = 25, t = 50, t = 85 and t = 135 days. One control microcosm and three treated microcosms were analysed in each time interval. Acute toxicity of water samples was assessed with Ceriodaphnia silvestrii Daday, 1902 and that of bulk sediment samples with Chironomus xanthus Rempel, 1939. Toxicity tests were carried out concomitantly with chemical analyses of dissolved inorganic nitrogen species (ammonia, nitrate and nitrite), sulfate and metals in the water samples of the microcosms. Acid volatile sulfides (AVS), simultaneously extracted metal (SEM) and potentially bioavailable metal were analyzed in bulk sediment samples. Neither of the tested organisms showed toxicity in the control microcosm samples. The water column of the treated microcosm showed toxicity to C. silvestrii, starting at t = 10 days, while the sediment pore water toxicity started at t = 0 day. However, toxicity was found to decline from t = 85 days to t = 135 days. Sediments showed toxicity to C. xanthus during the entire experiment, except at the longest incubation time (t = 135 days). The overall results indicate that nitrate, which reached concentrations exceeding 1,200 mg N-NO 3 -L -1 in the sediment pore water of the treated microcosms, was most probably responsible for the toxicity of the samples. Although the calcium nitrate technology proved effective in retaining phosphorus, promoting sediment oxidation via denitrification, from the ecotoxicological standpoint and under the experimental conditions of this study, the application of nitrate for remediation of the sediments in the Ibirité reservoir did not prove effective up to a period of 135 days of incubation. However, we presume that after longer periods of incubation, treated sediments may recover their ability to sustain a benthic community. More advanced experiments are planned involving longer incubation times, thus extending the denitrification process, which may lead to a higher phosphorus retention capacity and to more complete abatement of sediment toxicity. Keywords

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

Zebrafish (Danio rerio) é um proeminente organismo utilizado como modelo para a avaliação da segurança e eficácia de novos compostos na saúde animal de maneira rápida e econômica. Considerando que, anualmente, mais de mil novas substâncias são introduzidas no mercado para o desenvolvimento de produtos como vacinas, medicamentos, aditivos alimentares e agroquímicos, o objetivo deste artigo é apresentar uma revisão do emprego do Zebrafish como modelo animal destinado a avaliação da eficácia e da biotoxidade de compostos em pesquisas em medicina veterinária. Diversos estudos confirmam que os perfis entre Zebrafish e mamíferos são surpreendentemente semelhantes, sendo que sua transparência, fertilização externa, pequeno porte e curto ciclo de vida permitem a avaliação direta in vivo e em tempo real dos (i) efeitos de compostos químicos no desenvolvimento animal, (II) eficácia de novas drogas no tratamento de doenças específicas, (iii) eficácia e segurança no desenvolvimento de vacinas contra doenças infecciosas, (iv) direcionamento de tratamento do câncer animal de forma direcionada e específica. Desta forma, a praticidade e eficiência deste modelo animal nas pesquisas pode acelerar o processo de desenvolvimento de novos compostos veterinários quando comparado com pesquisas realizadas em outros modelos animais, e com maior valor preditivo e informativo que pesquisas conduzidas com ensaios in vitro.

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.