Chronic abamectin induces hepatotoxicity and endoplasmic reticulum stress in largemouth bass (Micropterus salmoides): Potential mitigation by curcumin and human health risk assessment.

Extensive use of abamectin (ABA) in agriculture and aquaculture raises ecological concerns due to its persistence and toxicity in aquatic environment. Thereby, current study evaluated the toxicological effects of ABA (0.012 mg/L) on largemouth bass and assessed the protective potential of curcumin (CUR) at dietary doses of 50, 100, and 200 mg/kg for six weeks. ABA exposure significantly reduced survival (71-82 %) (group B and C, p < 0.05), induced behavioral abnormalities, and caused severe liver damage, while CUR supplementation (particularly at 200 mg/kg) improved survival, behavior, and tissue integrity. CUR's detoxifying properties were further evidenced by its ability to ameliorate oxidative stress, as it restored antioxidants and significantly reduced MDA level, that was induced via the Nrf2/Keap1 signaling pathway. Additionally, CUR effectively reduced inflammation and immune dysfunction; which was induced through NF kB/p38-MAPK pathway, by downregulating pro-inflammation cytokines (il-8, tnf-α, il-1β) and anti-inflammation markers (tgf-β1, il-10). Furthermore, ABA had induced apoptosis by Bax/Bcl2/Cas-3 pathway, as indicated by elevated caspase and bax expression, that was counteracted by CUR treatment which had increased bcl2 level (p < 0.05). CUR treatment had partially mitigated the ABA activated autophagy, indicated by redcued lc3 II and p62 gene expression. ABA-induced ER stress through the grp78/IRE1α/CHOP pathway, with CUR showing attenuating role for stress marker expression (p < 0.05). Importantly, CUR reduced the bioaccumulation of ABA in the liver and muscles, decreasing potential risks to human health through fish consumption. Overall, CUR significantly mitigated ABA-induced hepatotoxicity, oxidative stress, inflammation, apoptosis, autophagy, and ER stress. These findings highlighted the potential detoxification role of CUR against ABA toxicity in aquaculture, improving fish health and reducing the risk of pesticide residues in fish consumed by humans.