Acetochlor Induces Nephrotoxicity in Chicken through IP3R1-GRP75-VDAC1-Mediated Stabilization of Mitochondria-Associated MAMs and the Regulation of Apoptosis and Autophagy, an Effect That Is Mitigated by Omega-3 Fatty Acids.

Acetochlor (ACT)-induced nephrotoxicity in poultry remains poorly understood. 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)-mitochondria 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-Cytc-Caspase3 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.