Nanocerium Dioxide Prevents Renal Ischemia-Reperfusion Injury by Reducing Oxidative Stress and Inflammatory Response

Renal ischemia-reperfusion (IR) injury (RIRI) is the main cause of acute kidney injury (AKI) and is a common disease with high morbidity and mortality. However, due to the lack of effective diagnostic and therapeutic tools, patients with RIRI are often treated conservatively. In view of this, Professor Wu Yuzhang, Professor Zhou Xinyuan, Professor Yang Xiaochao, and Professor Jiang Jun of the Third Military Medical University developed a new preventive strategy, which is to use cerium dioxide nanoparticles (CNPs) for pretreatment before surgery.

Nanocerium dioxide prevents Key points:

1. Three different sizes of CNPs were experimentally synthesized, namely 46 nm (NP46), 81 nm (NP81) and 118 nm (NP118). Among them, NP118 can be used as an effective preventive drug for RIRI and its subsequent renal fibrosis. Studies have shown that CNPs can exhibit good antioxidant and anti-inflammatory activities in vitro and effectively protect the kidneys from RIRI and renal fibrosis in vivo. Relative to the RIRI group, renal lesions, serum creatinine, blood urea nitrogen, apoptotic cells, KIM-1 expression, and fibrosis area were all reduced in samples treated with CNPs. Mechanistic studies have found that CNPs not only reduce oxidative stress by regulating the Nrf2 pathway, but also reduce macrophage infiltration, M1 phenotype polarization, and the production of pro-inflammatory cytokines and chemokines, thereby attenuating the inflammatory response induced by RIRI.

2. In vitro experimental results further showed that CNP pretreatment not only significantly reduced intracellular ROS production in renal tubular epithelial cells and vascular endothelial cells but also effectively reduced lipopolysaccharide-induced inflammatory response in RAW264.7 cells. In addition, the researchers also found that a quarter of NP118 persisted in the IR kidney for more than 21 days. Among the three sizes of CNPs, NP118 performed the best in all experiments.

Taken together, this study fully demonstrates that CNPs can be used as a potential strategy to treat or prevent RIRI and renal fibrosis.