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This study investigated the renal toxicity of ACT in chickens and evaluated the protective effects of Omega-3 supplementation using molecular dynamics simulations, Western blotting, and immunofluorescence staining. Prolonged ACT exposure induced renal histopathological damage, mitochondrial swelling, and enhanced endoplasmic reticulum (ER)\u2013mitochondria coupling. Mechanistically, ACT promoted cytosolic calcium ([Ca2+]c) transfer to mitochondria, causing mitochondrial Ca2+ ([Ca2+]mit) overload, excessive mitochondrial ROS generation, mitochondrial permeability transition pore (mPTP) opening, activation of the Bax\u2013Cytc\u2013Caspase3 apoptotic pathway, and impaired autophagic flux. Omega-3 supplementation improved renal function, restricted [Ca2+]mit accumulation, reduced oxidative stress, maintained autophagic flux, and attenuated apoptosis. These findings indicate that inhibition of IP3R-GRP75-VDAC1-mediated [Ca2+]mit overload and oxidative stress, thereby preventing mPTP opening, may mitigate ACT-induced kidney injury and growth impairment. This study provides mechanistic insight into ACT nephrotoxicity and supports Omega-3 as a potential nutritional strategy for reducing related environmental risks.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05123","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:02:31Z","timestamp":1788980551000},"page":"29532-29549","source":"Crossref","is-referenced-by-count":1,"title":["Acetochlor Induces\nNephrotoxicity in Chicken through\nIP3R1-GRP75-VDAC1-Mediated Stabilization of Mitochondria-Associated\nMAMs and the Regulation of Apoptosis and Autophagy, an Effect That\nIs Mitigated by Omega-3 Fatty Acids"],"prefix":"10.1021","volume":"74","author":[{"given":"Hongmin","family":"Lu","sequence":"first","affiliation":[{"name":"Northeast Forestry University , , , ,","place":["Harbin, Heilongjiang, P. R. China, 150040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Northeast Forestry University , , , ,","place":["Harbin, Heilongjiang, P. R. China, 150040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Northeast Forestry University , , , ,","place":["Harbin, Heilongjiang, P. R. China, 150040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Northeast Forestry University , , , ,","place":["Harbin, Heilongjiang, P. R. China, 150040"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Dong","sequence":"additional","affiliation":[{"name":"Northeast Forestry University , , , ,","place":["Harbin, Heilongjiang, P. R. 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