Reversing Acute Kidney Injury Through Coordinated Interplay of Anti-inflammation and Iron Supplementation.

Abstract

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD+ ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, we herein use an ultra-small Fe3 O4 nanoparticle as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD+ . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe3 O4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD+ precursor into renal cells through nicotinamide riboside kinase 1 on cell membrane. It was demonstrated that NMN-loaded Fe3 O4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicated that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previously strategies centering on anti-ROS (reactive oxygen species), anti-inflammation or even iron elimination. This article is protected by copyright. All rights reserved.