Reimagining Preclinical Research: Zebrafish Models Driving Advances in Pharmacology and Toxicology

<ns3:p> The increasing demand for ethically acceptable, economically viable, and translationally relevant animal models in biomedical research positions <ns3:italic>Danio rerio</ns3:italic> (zebrafish) as a prominent alternative to traditional rodent systems. This review provides an integrated analysis of zebrafish biology and delineates their expanding applications in pharmacological investigations and toxicological evaluations. Emphasis is placed on genetic homology with humans, optical transparency during embryogenesis, and suitability for high-throughput screening, which collectively support the model’s relevance in contemporary biomedical studies. The historical progression of zebrafish usage is outlined, and critical biological features, such as developmental kinetics, sexual dimorphism, and organogenesis are described to contextualize their utility in disease modeling. Zebrafish are examined for their capacity to assess acute, chronic, and specialized toxicity endpoints, including neurotoxicity, hepatotoxicity, and endocrine disruption. Their roles in investigating inflammation, metabolic disorders, neurodegeneration, cancer, and infectious diseases are also reviewed. Technological advancements, including CRISPR/Cas9-mediated gene editing and the development of transgenic lines, are discussed alongside innovations in imaging and screening methodologies. Regulatory frameworks, as well as compliance with Good Laboratory Practices (GLP), are addressed. The review concludes by evaluating the potential of zebrafish in precision medicine and their capacity to enhance early-phase drug discovery through scalable, cost-effective, and biologically relevant approaches. </ns3:p>