A Comprehensive Review of Zebrafish Models in Pharmacological and Toxicological Investigations

ABSTRACT

In recent years, the zebrafish ( Danio rerio ) has become a prominent vertebrate model for toxicological and pharmacological research. Over 70% of its genome shares orthologous sequences with that of humans, establishing it as a genetically manipulable system that mirrors significant drug–target interactions and pathways associated with human diseases. While external fertilization and fast growth (organ function within 96–120 h) are made possible by transparent embryos and larvae, real‐time, noninvasive monitoring of organogenesis and cellular processes is also made possible. Enable multi‐well formats for high‐throughput phenotypic screening. These characteristics, together with affordable housing expenses and adherence to the 3R ethical standards, make zebrafish an ethically and financially advantageous substitute for mammalian models. Its predictive value for developmental, neuro, and cardiotoxicity evaluations has been validated by comparative studies that show ≥ 80% concordance between zebrafish toxicity findings and mammalian data. Recent developments allow for exact dose–response modeling, metabolic profiling, and mechanistic dissection of oxidative stress, ER stress, inflammation, and apoptotic pathways by combining zebrafish tests with quantitative systems pharmacology. Additionally, zebrafish are being used more and more in environmental toxicology to examine the effects of pollutants on behaviors and neurodevelopment, bridging the gap between risk assessment for human health and the environment. The zebrafish model, when utilized in combination, provides significant experimental throughput and relevance for translation and accelerates safety pharmacology, toxicological mechanistic studies, and the process of drug development.