In healthy animals, a single exposure to gadoteric acid (Gd-DOTA), a magnetic resonance imaging contrast agent, induced some alterations in renal and inflammatory biomarkers, that attenuate over time, while leaving detectable gadolinium deposits in the body. These data highlight the need for further investigation of Gd-DOTA–induced renal effects, mainly under conditions of increased vulnerability. This project aims to elucidate the cellular and molecular mechanisms of Gd-DOTA–induced nephrotoxicity in human proximal tubular (HK-2) cells under stress conditions relevant to kidney injury, including proteinuria (increased albumin in the culture medium) and inflammation (induced by TNF-α and IL-1β). We will also assess potential protective effects of N-acetylcysteine (antioxidant) and galangin (anti-inflammatory/antioxidant). Cell death and oxidative stress will be evaluated at cellular and mitochondrial levels, along with key mediators of inflammatory and stress-related signaling pathways. The data generated in this project will contribute to a better understanding of the mechanisms of Gd-DOTA–induced
nephrotoxicity and support the development of preventive and therapeutic strategies.