Impact of chronic sub-lethal methylparaben exposure on cardiac hypoxia and alterations in neuroendocrine factors in zebrafish model

Background Endocrine-disrupting chemicals have been shown to cause toxicity in different systems of the body including the endocrine, cardiovascular and nervous systems. This study aims to analyze the adverse effects of Methylparaben (MP) on cardiac functions, neurodevelopment, and behavior of zebrafish. Methods and results Adult male and female zebrafish were exposed to MP for 30 days to study the toxicity effects. Zebrafish were grouped into control, solvent control, 1/10th (110 ppb), 1/100th, and 1/1000th (1 ppb) lethal concentration 50 of MP. Neurobehavioral assays, acetylcholinesterase (AChE) activity, serotonin levels, and expression of genes-Hypoxia-inducible factor 1 alpha, Neurotrophic Receptor Tyrosine Kinase, Paired box protein Pax-6, and tnnt2 were investigated in zebrafish. Results of the study showed more anxiety-like behavior in MP-treated female zebrafish when compared to males on chronic exposure. There was a dose-dependent reduction of AChE activity in both male and female zebrafish. Female zebrafish showed a dose-dependent increase in serotonin level on MP exposure while male zebrafish showed a dose-independent decrease in serotonin level. On MP exposure, there was also a dose-dependent dysregulation in the expression of cardiac hypoxia and neuronal differentiation-related genes in female zebrafish while a dose-independent change was observed in male zebrafish. Conclusion Chronic MP exposure affects cardiac functions, neuronal functions, and behavior of zebrafish by exhibiting changes in AChE activity, serotonin levels, and altering the expression of genes related to cardiac hypoxia and neuronal differentiation even at sub-lethal doses.