Zebrafish is an ideal model to assess environmental toxicity. In zebrafish, both renal function and the glomeruli structure are similar to mammals, enabling the comparison of histopathology. The renal filtration process contributes to the excretion of compounds previously metabolized in the liver. The latter is accountable to perform the functions of the bone marrow, absent in zebrafish. The kidneys have lymphoid, endocrine, and hematopoietic tissues.

However, despite these structural divergences, there are conserved aspects compared to the liver of mammals, for instance, the presence of hepatocytes and their main physiological processes performed through the action of the cytochrome P450, which makes it possible to compare hepatic lesions caused by nocive compounds in humans. The liver of zebrafish has disorganized hepatocytes and lacks Kupffer cells accountable to phagocyte foreign bodies. The major organs accountable to metabolize and excrete xenobiotics are the liver and the kidney. Therefore, tissue changes are a useful tool to assess how a tested compound can exert a toxic in the animal for this, it is essential to choose the most appropriate organs to be assessed. The sensibility of zebrafish organs to harmful compounds makes it possible to appraise through histopathology the safety of potentially bioactive substances. Zebrafish has been gaining attention for toxicological assays, either of administered compounds or those present in the environment due to its physiological response and histological features similar of those of mammals, potentially reducing the number of rodents used in the laboratory routine. In pharmacology, determining the toxicity of the tested compound is a crucial step in preclinical studies since it will be the base for clinical trials when it is tested in humans. Despite the phylogenetic distance, zebrafish has about 70% of genetic homology toward humans hence, it is considered a reliable tool for preclinical studies. Due to its small size and low body weight, it requires a relatively low quantity of the compound tested, which is an excellent advantage in the research. The exponential growth of zebrafish use in laboratories is due to several favorable features such as its fast life cycle (the adult stage reached about 6 months), high fecundity (hundreds of eggs are laid in each mating), transparency of the embryonic/larval stages which facilitates the observation of the development, low maintenance cost, and easy handling. Since the first use of zebrafish as an experimental model in 1955, it has been consolidated as a model organism for biology, genetics, pharmacology, and general biomedical research. The species often adapts to environmental changes of temperature and pH. It has a small size and reaches up to 5 centimeters of length. It is natural of Bangladesh, Nepal, and India and is popularly sold as an ornamental fish. Zebrafish ( Danio rerio) is a teleost fish from the family Cyprinidae, inhabiting fresh water of tropical regions. *Address all correspondence to: Introduction Laboratório de Pesquisa em Fármacos, Curso de Farmácia, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Brazil.Programa de Pós-graduação em Ciências Farmacêuticas, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Brazil.

Based on the information presented here, it is expected that the researcher recognizes differences between healthy and changed tissue, without having to compare its result with other species. This chapter brings together histopathological nonclinical toxicity studies performed exclusively with zebrafish, highlighting significant histological changes found in its gills, liver, kidneys, and intestine. In such cases, the choice of the organ assessed relies on the type of compound tested, administration route, and biological activity. The digestive, cardiovascular, urinary, nervous, and reproductive systems of zebrafish display feature similar to those of superior mammals, and due to its susceptible organs, the adult zebrafish has been used to test the toxicity of environmental compounds and potential drug candidates through histopathology analysis complementarily with other parameters.

These features make zebrafish an attractive and promising model organism for nonclinical tests due to the ease of handling and cost–benefit compared to other models. Zebrafish (Danio rerio) is a small-sized teleost fish natural of tropical regions, with a short life cycle and high homology toward humans.

Zebra fish