#5050 ANTIOXIDANT PORPHYRIN-BASED NANOZYME WITH SINGLE RUTHENIUM FOR TREATMENT OF ACUTE KIDNEY INJURY

نویسندگان

چکیده

Abstract Background and Aims Acute kidney injury (AKI) describes a sudden loss of function characterized by elevated serum creatinine (CRE) levels reduced urinary output. AKI patients have high mortality rate, but limited treatment options are currently available. During the progression, an excess reactive oxygen species (ROS) leads to oxidative stress, which often results in cell damage renal failure. Therefore, ROS scavenging has been considered promising strategy for treatment. Here we report porphyrin-based nanozyme with single ruthenium (Por-Ru) as scavenger cure AKI. Method The Por-Ru was synthesised one-pot synthesis. First, 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (Por) added solvent containing N, N-dimethylformamide. RuCl3 then introduced form Ru-N coordinated porphyrin networks. We analysed morphology chemical structure using scanning electron microscopy (SEM) X-ray photoelectron spectroscopy (XPS). also tested its enzyme-mimicking abilities scavenge ROS. catalase-like (CAT) property peroxide-titanium complex method, superoxide dismutase-like (SOD) •O2− assay. In vitro, protective effect against examined mouse tubular epithelial (TCMK-1) line. After biocompatibility evaluation, therapeutic efficacy investigated glycerol-induced mice. Results 1. Characterizations nanozyme: SEM image showed spherical average diameter 6-8 nm (Figure 1a). Meanwhile, XPS revealed presence Ru detailed elemental components 1b). As shown Figures 1c d, had excellent CAT-like SOD-like capabilities. Furthermore, DPPH• assay confirmed antioxidant 1e). 2. Protective vitro vivo: counting kit-8 that not cytotoxic TCMK-1 cells at concentrations ranging from 10 100 µg/mL. further cytoprotective effects damage. flow cytometry intracellular level increased after H2O2, while obviously decreased addition 2a, b). H2O2-induced apoptosis investigated. 2c rate significantly nanozyme. Before vivo experiments, haemolysis found be less than 5% even dose 200 Additionally, toxicity assessment test no noticeable impacts on blood parameters, liver functions, histopathology major organs normal Then, 2e f, CRE urea nitrogen (BUN) mice treated were lower those group. haematoxylin eosin (H&E) staining many casts (marked triangles) observed tissue mice, whereas obvious area Conclusion Our findings demonstrate anti-ROS experiments alleviated ROS-induced apoptosis. effectively improved attenuated Taken together, may become novel agent

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ژورنال

عنوان ژورنال: Nephrology Dialysis Transplantation

سال: 2023

ISSN: ['1460-2385', '0931-0509']

DOI: https://doi.org/10.1093/ndt/gfad063c_5050