Study of Metabolomic Markers of β-Blocker Neurotoxicity Using Zebrafish as a Model Organism.

Abstract

Using zebrafish (Danio rerio) as a model organism, we studied metabolomic markers of β-blocker neurotoxicity (propranolol, metoprolol, bisoprolol) and the relationships between neurotransmitter disturbances (dopamine, epinephrine, choline, cortisol) and their effects. Propranolol produced the most pronounced changes: significant increases in cortisol and epinephrine and decreases in dopamine and serotonin levels. Metoprolol caused a moderate increase in cortisol while elevating serotonin, suggesting a more balanced pharmacological profile. Bisoprolol had virtually no effect on cortisol or monoamine levels but increased the concentrations of choline, glycine, and glutamate. Differences in neurometabolic effects of β-blockers were identified: propranolol demonstrated a strong neurotoxic potential, consistent with its depressive side effects in humans; metoprolol showed an intermediate effect; while bisoprolol did not affect CNS. Zebrafish exhibited high sensitivity to neurochemical shifts, making this model valuable for preclinical drug neurotoxicity assessment.