Locomotor activity alterations in zebrafish following cisplatin exposure: An assessment of neurobehavioral toxicity

Cisplatin is a widely used chemotherapeutic agent for treating solid tumors. However, its extensive clinical application raises environmental concerns, as it has been detected in wastewater effluents at concentrations as high as 150 μg/L. Even though recent studies indicate that even sub-lethal concentrations of cisplatin may induce neurobehavioral toxicity in aquatic organisms, the precise mechanism underlying cisplatin-induced behavioral disturbances remains unclear. Considering the above and that the neurotoxic impact of cisplatin on aquatic vertebrates remains unexplored mainly, this study sought to address two key objectives: 1) to determine whether cisplatin induces neurotoxic effects in fish and 2) to investigate the mechanisms through which cisplatin may cause neurobehavioral changes in these organisms. The findings revealed that zebrafish exposed to cisplatin concentrations of 2, 5, and 10 μg/L experienced a marked reduction in locomotor activity, with pronounced periods of immobility and the emergence of anxiety-like behaviors. Furthermore, exposure to cisplatin over 96 h led to considerable disruptions in redox balance and acetylcholinesterase (AChE) activity, characterized by a pronounced enzymatic inhibition. Likewise, gene expression analyses further demonstrated that cisplatin exposure upregulated pathways associated with apoptosis and mitochondrial dysfunction while concurrently downregulated pathways linked to neuronal protection and muscle development. Overall, these findings underscore cisplatin's broad and multifaceted effects on zebrafish, involving both behavioral and biochemical alterations.