Maresin-1 alleviates sepsis-induced acute kidney injury by inhibiting ferroptosis via the Nrf2/HO-1/Gpx4 signaling pathway

Sepsis-induced acute kidney injury (S-AKI) is a severe complication of sepsis. This study aimed to explore the protective effects of Maresin-1 (MaR-1) on S-AKI and elucidate its potential molecular mechanisms, focusing on ferroptosis and the Nrf2/HO-1/GPx4 signaling pathway. <i>In vitro</i> cellular experiments and <i>in vivo</i> mouse models of S-AKI were employed. Cell viability, ferroptosis-related markers (reactive oxygen species [ROS], malondialdehyde [MDA], and iron ion concentration), and antioxidant protein expression were analyzed. The Nrf2/HO-1/GPx4 signaling pathway was examined using Western blotting. <i>In vivo</i>, renal injury markers (blood urea nitrogen [BUN], serum creatinine [SCr], and neutrophil gelatinase-associated lipocalin [NGAL]) and ferroptosis indicators in kidney tissues were assessed. Nrf2 knockdown was used to validate its role in MaR-1-mediated effects. MaR-1 significantly improved cell viability and reduced ferroptosis-related markers (ROS, MDA, and iron ion concentration) <i>in vitro</i>. It also upregulated antioxidant proteins through theNrf2/HO-1/GPx4 signaling pathway. In the mouse model, MaR-1 administration decreased renal injury markers (BUN, SCr, NGAL) and ferroptosis-related indicators in kidney tissues. Nrf2 knockdown markedly attenuated MaR-1’s protective effects,highlighting the essential role of this pathway in mitigating ferroptosis. This study demonstrates that MaR-1 alleviates S-AKI by inhibiting ferroptosis through activation of theNrf2/HO-1/GPx4 signaling pathway. These findings provide insights into the potential therapeutic application of MaR-1 for S-AKI. Maresin-1 attenuates sepsis-induced acute kidney injury by suppressing ferroptosis.Nrf2/HO-1/GPx4 signaling is essential for the protective effects of Maresin-1.Therapeutic potential of Maresin-1 in sepsis-induced organ injury. Maresin-1 attenuates sepsis-induced acute kidney injury by suppressing ferroptosis. Nrf2/HO-1/GPx4 signaling is essential for the protective effects of Maresin-1. Therapeutic potential of Maresin-1 in sepsis-induced organ injury.