Commercial green propolis mitigates ivermectin-induced functional toxicity but not morphological abnormalities in...

Ivermectin, a macrocyclic lactone used in veterinary medicine and aquaculture, can pose risks to non-target aquatic organisms. Although its developmental toxicity in fish is well documented, mitigation strategies remain poorly explored, and the protective potential of commercial green propolis has not been investigated. This study evaluated whether a commercial aqueous extract of green propolis mitigates ivermectin embryotoxicity in zebrafish (Danio rerio). Embryos were exposed to ivermectin or green propolis (100, 200, 400, and 800 µg.L^-1) from 6 to 120 h post-fertilization. For co-exposure, the lowest ivermectin concentration that caused significant mortality (200 µg.L^-1; 35% mortality, p = 0.02) was combined with 200 µg.L^-1 of green propolis. Mortality, hatching rate, heart rate, length, and malformations were assessed. Ivermectin induced concentration-dependent toxicity, with mortality reaching 55% at 400 µg.L^-1 (p < 0.001) and 73% at 800 µg.L^-1 (p < 0.001), alongside impaired hatching, increased heart rate, and growth retardation. Green propolis alone resulted in mortality rates below 22% across all tested concentrations. Co-exposure significantly reduced mortality from 35% to 5% (χ² = 16.88, p = 3.99 × 10^-5), yielding a 30% absolute and 85.7% relative risk reduction. Co-exposure also improved hatching rate, did not differ significantly from control levels in heart rate, and increased larval length compared to ivermectin alone. However, propolis failed to prevent morphological abnormalities, including yolk sac and pericardial edemas, tail curvature, and craniofacial defects. In conclusion, commercial green propolis effectively mitigates ivermectin-induced functional toxicity in zebrafish embryos but is insufficient to prevent structural malformations.