Journal Article

Polyethylene glycol capped gold nanoparticles ameliorate renal ischemia–reperfusion injury in diabetic mice through AMPK-Nrf2 signaling pathway

Salama, Mohamed, Saleh, Hanan, Hussein, Rehab Mohamed

2022

Overview

The aim of this study is to investigate the protective effect of polyethylene glycol capped gold nanoparticles (PEG-AuNPs) on renal ischemia–reperfusion injury (I/R)–induced acute kidney injury (AKI) in diabetic mice via the activation of adenosine 5′ monophosphate–activated protein kinase—nuclear factor erythroid-2-related factor-2 (AMPK-Nrf2) pathway. Diabetes was induced in male mice (12/group) by streptozotocin (50 mg/kg) for 5 consecutive days. After 4 weeks, the mice have intravenously received doses of PEG-AuNPs (40, 150, and 400 µg/kg body weight) for 3 consecutive days, and then animals were subjected to 30 min ischemia and 48 h reperfusion. Following the treatment with three different doses of PEG-AuNPs, the levels of blood urea nitrogen (BUN) and creatinine were reduced. Obvious reduction in renal tubular atrophy, glomerular damage, mitochondrial damage, and necrotic area were ultra-structurally detected, and renal interstitial inflammation and apoptosis were diminished. Moreover, PEG-AuNPs increased the recovering of damaged renal cells, suppressed significantly levels of malondialdehyde (MDA), downregulated significantly the level of inflammatory cytokines (TNF-α and IL-1β), and upregulated the AMPK-Nrf2 pathway. PEG-AuNPs exhibited a promising alternative therapeutic target for diabetic renal I/R-induced AKI through upregulation of AMPK/PI3K/AKT path which additionally stimulated Nrf2-regulated antioxidant enzymes in a dose-dependent manner. Graphical abstract

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: 1-Phosphatidylinositol 3-kinase / acute kidney injury / Acute Kidney Injury - drug therapy / Acute Kidney Injury - metabolism / adenosine / Adenosine - metabolism / Adenosine - pharmacology / Adenosine - therapeutic use / Adenosine monophosphate / AKT protein / AMP / AMP-Activated Protein Kinases - metabolism / AMP-Activated Protein Kinases - pharmacology / Animals / antioxidants / Antioxidants - metabolism / Apoptosis / Aquatic Pollution / Atmospheric Protection/Air Quality Control/Air Pollution / Atrophy / blood / Body weight / Creatinine / Creatinine - metabolism / Cytokines / Damage / Diabetes / Diabetes mellitus / Diabetes Mellitus, Experimental - drug therapy / dose response / Earth and Environmental Science / Ecotoxicology / Environment / Environmental Chemistry / Environmental Health / Environmental science / Gold / Gold - pharmacology / IL-1β / Inflammation / Injuries / intravenous injection / Ischemia / Kidney / Kidneys / Kinases / Male / males / malondialdehyde / Malondialdehyde - metabolism / Metal Nanoparticles / Mice / Mitochondria / nanogold / Nanoparticles / NF-E2-Related Factor 2 - metabolism / Oxidative Stress / Phosphatidylinositol 3-Kinases - metabolism / Polyethylene glycol / Polyethylene Glycols - metabolism / Polyethylene Glycols - pharmacology / protective effect / Protein kinase / Proto-Oncogene Proteins c-akt - metabolism / Reperfusion / Reperfusion Injury - drug therapy / Research Article / Signal Transduction / Streptozocin / Streptozocin - metabolism / Streptozocin - pharmacology / Streptozocin - therapeutic use / streptozotocin / Therapeutic targets / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α / Urea / urea nitrogen / Waste Water Technology / Water Management / Water Pollution Control