The interaction between paracetamol and ethanol during the early development of zebrafish

The issue of drug-alcohol interactions is a major concern in drug therapy and can endanger patient safety. Paracetamol is one of the most widely used analgetic drugs, while ethanol is commonly consumed addictive substance. This study investigated the toxic effects of paracetamol, ethanol, and their mixture at different concentrations on the embryonic development of zebrafish (Danio rerio, D. rerio).

Zebrafish embryos (20 embryos per group, 3 biological replicates for each concentration or combination of concentrations) were exposed for 72 h post-fertilization to paracetamol (0.5, 1.0, 2.0, 3.0, 5.0, and 10.0 mM), ethanol (85.5, 171.0, 256.5, 342.0, 513.0, 855.0) or their combinations. Additionally, combinations of paracetamol and ethanol were examined to assess the type of interaction (0.5:85.5; 1.0:171.0; 1.5:256.5; 2.0:342.0; 3.0:513.0; and 5.0: 855.0 mM).

The combination of the drug and alcohol resulted in a higher incidence of developmental defects compared to the effects of either substance used alone. The most frequently observed changes included decreased larval pigmentation, pericardial and sac edema or increased larval mortality compared to control (e.g., 2-4 fold increase over control). Notably, there was a statistically significant reduction in both eye size and body length of the larvae. Furthermore, the severity of the defects increased proportionally with dose. Additionally, analysis using the Chou-Talalay method revealed the synergism in this interaction, with a combination index below 1.

These findings demonstrate that exposure to paracetamol and ethanol exerts a synergistic toxic effect on early zebrafish development, emphasising the potential risks associated with drug-alcohol co-exposure.