Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Abstract

Ischemia reperfusion (I/R) injury is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. NMDA receptor inhibitor (DAP5) and resveratrol (Res) could ameliorate kidney I/R injury, but their use is limited by low aqueous solubility and poor stability. Here, we examined the potential protective effects of Res-DAP5 nanoparticles (NP) against renal I/R injury. Mice were subjected to renal ischemia for 30 min followed by reperfusion for 24 h. The results showed that Res-DAP5-NP could decreased serum creatinine (Cr) and urea nitrogen (BUN), alleviated tubular damage and oxidative stress. In addition, Res-DAP5-NP suppressed cell apoptosis, promoted the expression of p-DAPK, and inhibited the expression of p-CaMK and p-AKT. Furthermore, Res-DAP5-NP decreased the production of pro-inflammatory cytokines such as tumor necrosis factor-α, IL-1β, IL-6, and p-IκBα induced by renal I/R injury. In addition, Res-DAP5-NP also attenuated renal I/R injury in vivo, as manifested by increase in cell viability, SOD level, and the expression of p-DAPK, decreases in intracellular Ca²⁺ concentration and the expression of p-CaMK. Taken together, our findings indicates that Res-DAP5-NP could effectively protect renal I/R injury by inhibiting apoptosis and inflammation responses, possibly through AKT/NMDA/CaMK/DAPK and NF-κB pathways.