Hepatotoxicity of imidacloprid in zebrafish and the alleviating role of 10-hydroxy-2-decenoi acid: insights into oxidative stress, inflammation, and gut microbiota

Abstract

Imidacloprid (IMI), a widely used neonicotinoid pesticide, is commonly found in environmental residues and threatens organism health, especially hepatotoxicity. 10-Hydroxy-2-decenoic acid (10-HDA), a natural compound in royal jelly with recognized anti-inflammatory and antioxidant properties, has garnered interest; however, its potential in mitigating pesticide-induced hepatotoxicity remains underexplored. This study evaluated the toxic effects of IMI and the hepatoprotective role of 10-HDA in zebrafish. The results demonstrated that both acute and chronic IMI exposure (4 mg/L for 48 h in larvae; 1 mg/L for 14 d in adults) induced severe liver injury in zebrafish, manifested as elevated aminotransferase activity, histopathological alterations, enhanced hepatocyte apoptosis, dysregulated oxidative stress biomarkers, and increased reactive oxygen species (ROS) levels. Concurrently, IMI exposure activated the NF-κB signaling pathway, triggering inflammatory responses in hepatic and intestinal tissues. 16S rRNA sequencing revealed that IMI disrupted gut microbial balance, reduced diversity, and enriched pathogenic bacteria such as Plesiomonas shigelloides, suggesting a role of the gut-liver axis in hepatotoxicity. Notably, 10-HDA treatment (0.5 and 1 mM for 48 h in larvae; 1 and 10 mg/L for 14 d in adults) effectively alleviated IMI-induced damage by reducing oxidative stress, suppressing inflammation, and restoring gut microbiota homeostasis. In conclusion, the present study emphasized the hepatotoxicity of IMI and demonstrated for the first time that 10-HDA was able to counteract IMI-induced liver injury through multi-mechanism regulation such as the gut-liver axis, providing new insights into pesticide toxicity interventions based on natural compounds.