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.

Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury

“…Moreover, inflammation is a key factor in the occurrence and development of ischemic damage, which is secondary to an intense inflammatory response [32]. Therefore, the inhibition of apoptosis and inflammation might serve as an effective strategy to attenuate renal I/R injury [20]. Additionally, I/R injury was demonstrated to activate NF-κB signaling by releasing the NF-κB p65-p50 dimer and by degrading IκB [33,34].…”

“…A previous study by Li et al suggested that the pre-treatment with tea polyphenol could inhibit the TLR4/NF-κB signaling pathway, and consequently protect renal tubular epithelial cells against I/R-induced apoptosis [19]. Importantly, a recent report demonstrated that I/R-induced AKI could be suppressed when cell apoptosis is inhibited [20]. Therefore, the current study aims to investigate the effects of lentivirusmediated silencing of SHP-2, which regulates the TLR4/NF-κB signaling pathway, on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells in rats with renal I/R injury.…”

Apurinic/apyrimidinic endonuclease 1 (APE1) contributes to resveratrol-induced neuroprotection against oxygen-glucose deprivation and re-oxygenation injury in HT22 cells: Involvement in reducing oxidative DNA damage

“…We discussed the role of APE1 in resveratrol-elicited protective effect in cerebral ischemia injury only in terms of its antioxidant stress activity. Many researches revel that both APE1 and resveratrol have anti-apoptotic and anti-inflammatory activities (41)(42)(43), implying that apoptosis may also contribute to the role of APE1 in these. In addition, we only use HT22 cells to test the hypothesis.…”

The role of PAK1 in the sensitivity of kidney epithelial cells to ischemia-like conditions

“…Every year, multiple new agents are reported to elicit some nephroprotection in pre-clinical models (e.g. [40][41][42][43][44][45][46][47]), but the proof of their efficacy in human trials is still lacking, and, hence, the unmet need remains.…”