Zebrafish (Danio rerio): A potential model to assess developmental toxicity of ketamine

Ketamine is a non-competitive antagonist of NMDA glutamate receptor. It is used as an anesthetic, analgesic, sedative, and anti-depressive agent in clinical practice and also an illegal recreational drug. The increasing use has contributed to the measurable levels of ketamine in both wastewaters and hospital effluents, thereby classified as an emergent contaminant. Lately, the potential toxicity of ketamine has raised serious concerns about its iatrogenic or illicit use during pregnancy, neonatal and childhood stages. However, to assess its long-term toxicity potentially by the use of early life stages in human and rodents is limited. In this regard, the zebrafish has been considered as excellent model organism for biosafety assessments of ketamine due to it boasts an in vivo model with the advantages of an in vitro assay. In this review, we summarize the current understanding of the reported toxicity studies with ketamine in early life stage of zebrafish. The adverse effects of ketamine are known to cause overall developmental and multi-organ toxicity, including cardio-, neuro-, and skeletal toxicity. Furthermore, multiple mechanisms are found to be responsible for perpetrating toxicity of ketamine. The current findings confluence to emphasize the zebrafish embryo as an appealing model system for developmental toxicity testing in higher vertebrates.