Curcumin regulates ferroptosis by activating α7 nicotinic acetylcholine receptor to improve sepsis-induced acute kidney injury

Acute kidney injury (AKI) is a frequent complication of sepsis. It has been reported that curcumin can alleviate sepsis-associated AKI (SA-AKI). This study aims to elucidate the regulatory effects and mechanisms of curcumin on ferroptosis in the context of SA-AKI. In this study, septic mice and lipopolysaccharide-stimulated HK-2 cells were employed to simulate the pathological conditions of SA-AKI. The status of renal injury and ferroptosis-related indicators was determined to assess the regulatory effect of curcumin on ferroptosis in SA-AKI. Furthermore, the expression of α7 nicotinic acetylcholine receptor (α7nAChR) was intervened to investigate the specific protective mechanism of curcumin in SA-AKI. Finally, the nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385 was incorporated to further elucidate the potential pathway through which α7nAChR regulates ferroptosis. The results demonstrated that curcumin exerted a significant protective effect on SA-AKI cells and animal models, markedly reducing cellular damage and renal injury in mice, attenuating the inflammatory response, and effectively inhibiting ferroptosis in renal cells and tissues. Furthermore, curcumin treatment upregulated the expression of α7nAChR in both SA-AKI cells and animal models. Nevertheless, the inhibition of α7nAChR expression partially counteracted the ameliorative effects of curcumin on injury and ferroptosis in SA-AKI cells and animal models. The overexpression of α7nAChR attenuated LPS-induced ferroptosis in HK-2 cells, whereas ML385 reversed the inhibitory impact of α7nAChR upregulation on cellular ferroptosis. In conclusion, these findings indicate that curcumin suppresses ferroptosis by upregulating α7nAChR to activate the antioxidant capacity of NRF2, thereby providing a protective effect against SA-AKI.