Developmental and neurobehavioral toxicity of di-(2-ethylhexyl) phthalate (DEHP) in zebrafish larvae

Di-ethyl hexyl phthalate (DEHP), a plasticizer used in medical devices and cosmetics, easily leaches into the environment due to its weak chemical bonds with plastics. Humans and other organisms are exposed to DEHP through inhalation, ingestion, and dermal contact, inflicting toxic effects like neurotoxicity, hepatotoxicity, and reproductive toxicity. However, there is a lack of information on its developmental toxicity, and its role in demyelination is also not well understood. We explored the adverse effects of DEHP during the early developmental stage of zebrafish larvae, focusing on its deteriorative impact on the nervous system through demyelination at various concentrations (10, 20, 50, 100, and 200 ppm). Cuprizone was used as a positive control compound. Various markers of oxidative stress, hormonal changes, and altered expression of myelin-related protein were measured in larvae exposed to DEHP. Results showed that higher concentrations of DEHP had lethal effects on zebrafish larvae. The activity of acetylcholinesterase (AChE) and the level of reduced glutathione (GSH) were significantly decreased, while lipid peroxidation (LPO) and glutathione S-transferase (GST) activity were significantly increased. Additionally, cortisol and thyroxine levels were notably decreased, together with decreased mRNA expression of the myelin sheath and its cell markers such as myelin basic protein (mbp), SRY-box transcription factor (sox10), and oligodendrocyte lineage transcription factor 2 (olig2) in the DEHP-treated larvae. Similarly, protein expression of Mbp, Sox10, and Olig2 was also reduced. Overall, this study offers an understanding of the developmental neurotoxicity of DEHP and its behavioral and demyelinating effects in zebrafish larvae during early developmental stages.