Omega-3 Fatty Acids Attenuate LPS-Induced Acute Kidney Injury via Activation of AMPK/SIRT1/PGC-1α/NRF2/FOXO3 Signaling and Suppression of NF-κB-Mediated Inflammation

<b>Background:</b> Sepsis-induced acute kidney injury (AKI) involves oxidative stress and inflammation. Omega-3 (OMG-3) fatty acids possess antioxidant properties, but their impact on the mitochondrial AMPK/SIRT1/PGC-1α/NRF2/FOXO3 axis in AKI remains unclear. <b>Methods:</b> Thirty-two male Wistar rats were divided into Control, LPS (5 mg/kg), LPS + OMG-3 (500 mg/kg/day), and OMG-3 groups. Renal tissues were analyzed for histopathology, immunohistochemistry (<i>TNF-α</i>, <i>Caspase-3</i>, <i>HSP70</i>), and gene expression (<i>AMPK</i>, <i>SIRT1</i>, <i>PPGC-1α NRF2</i>, <i>FOXO3</i>). <b>Results:</b> LPS caused severe tubular injury, increased <i>TNF-α</i>, <i>Caspase-3</i>, and <i>HSP70</i> expression, while significantly downregulating the AMPK/SIRT1/PGPGC-1αRF2/FOXO3 signaling pathway. OMG-3 treatment alleviated histopathological damage, suppressed inflammatory and apoptotic markers, and restored the expression of mitochondrial and antioxidant genes. <b>Conclusions:</b> OMG-3 fatty acids protect against LPS-induced AKI by upregulating the gene expression of components in the <i>AMPK/SIRT1/PGCPGC-1αF2/FOXO3</i> axis and suppressing NF-κB-driven inflammation. This dual regulation highlights OMG-3 as a potential therapeutic agent for sepsis-related renal injury.