Mechanistic evaluation of abamectin-induced gill toxicity in largemouth bass and its modulation: An integrated histological, molecular, and in silico assessment.

Insecticides such as abamectin (ABA) pose a clear threat to aquaculture, since their lipophilic properties cause accumulation in water and fish tissues, leading to prolonged exposure and toxicity. Based on pre-experimental acute toxicity results, a sub-lethal concentration of 0.012 mg/L ABA was selected for chronic exposure to represent environmentally relevant and worst-case scenarios. Additionally, CUR was added as diet supplementation at level of 50, 100, and 200 mg/kg as modulating agent and experiment was conducted for six weeks. Histopathological analysis revealed extensive gill damage in ABA-exposed groups (Group B: severe damage; Groups C and D: moderate recovery; Group E: near-normal filaments), including hyperplasia, hypertrophy, lamellar curling, and epithelial rupturing. Antioxidant defenses (SOD, GSH-Px, CAT) were significantly suppressed in Group B, whereas CUR-treated groups (C-E) showed progressive restoration, with Group E reaching near-control levels. Tight junction integrity disrupted as evidenced by the downregulated transcription and translation of claudin 5, claudin 7, zo-1, and occludin in Groups B and C, while Groups D and E showed partial to full recovery. Immune dysfunction was evident in Group B, with elevated il-1β, il-8, il-15, tnf-α, and tgf-β1 and altered ACP and AKP activity. Apoptotic markers (fas, p53, bax, bcl-2, caspases 3/8/9) were altered predominantly in Group B, with CUR reducing these effects in Groups C-E. Autophagy was dysregulated in Group B via mtor, akt, pi3k, p62, and lc3ii expression, and partially restored by CUR. ABA residues significantly accumulated in gills (p < 0.01), raising concerns about its persistence in edible fish; and IBR index values further indicated the exposure risk of ABA. Molecular docking analysis confirmed the binding affinity of ABA and CUR with TGF-β and catalase (CAT), exhibiting binding energies of -9.0 and - 13.7 kcal/mol for ABA, and - 5.2 and - 7.1 kcal/mol for CUR, respectively. These interactions involved key residues through hydrogen bonding and hydrophobic forces, suggesting potential modulation of enzymatic activity and signaling pathways. All in all, these findings highlight the multifaceted toxicity of ABA in gills of edible fish species and underscore the need for safer, environmentally friendly alternatives in pest management. Moreover, CUR emerges as a promising dietary intervention to enhance the resilience of aquatic organisms to pesticide-induced stress.