Abstract Title:

Oral Delivery of Nanoparticle Urolithin A Normalizes Cellular Stress and Improves Survival in Mouse Model of Cisplatin-induced AKI.

Abstract Source:

Am J Physiol Renal Physiol. 2019 Sep 18. Epub 2019 Sep 18. PMID: 31532243

Abstract Author(s):

Dianxiong Zou, Raghu Ganugula, Meenakshi Arora, Mary B Nabity, David Sheikh-Hamad, M N V Ravi Kumar

Article Affiliation:

Dianxiong Zou


The popular anti-cancer drug cisplatin causes many adverse side-effects, the most serious of which is acute kidney injury (AKI). Emerging evidence from laboratory and clinical studies suggests that the AKI pathogenesis involves oxidative stress pathways; therefore, regulating such pathways may offer protection. Urolithin A (UA), a gut metabolite of the dietary tannin ellagic acid, possesses anti-oxidant properties, and has shown promise in mouse models of AKI. However, UA's therapeutic potential is constrained by poor bioavailability. We aimed to improve oral bioavailability of UA by formulating it into biodegradable nanoparticles that utilize a surface conjugated ligand targeting the gut-expressed transferrin receptor. Nanoparticle encapsulation of UA led to a 7-fold enhancement in oral bioavailability compared to native UA. Treatment with nanoparticle UA also significantly attenuated the histopathological hallmarks of cisplatin-induced AKI and reduced mortality by 63% in the mouse model. Expression analyses indicated that nanoparticle UA therapy coincided with oxidative stress mitigation and downregulation of Nrf2 and P53-inducible genes. Additionally, normalization of miRNA (miR-192-5p and miR-140-5p) implicated in AKI, PARP1 levels, anti-apoptotic signaling, intracellular NAD, and mitochondrial oxidative phosphorylation were observed in the treatment group. Our findings suggest that nanoparticles greatly increases the oral bioavailability of UA leading to improved survival rates in AKI mice, in part by reducing renal oxidative and apoptotic stress.

Print Options

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.