Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO(2) nanoparticles (CNPs) were selected from CeO(2) with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce(3+) to Ce(4+) could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNP(S) against oxalate-induced damage and the effect of CNP(S) on calcium oxalate crystallization were studied. CNP(S) could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNP(S) can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNP(S) as a potential for clinical prevention of crystalline kidney injury and crystal deposition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01726-w.