Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage

Abstract Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanopart...

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Main Authors: Jiwang Deng, Bangxian Yu, Zhenglin Chang, Sicheng Wu, Guanlin Li, Wenzhe Chen, Shujue Li, Xiaolu Duan, Wenqi Wu, Xinyuan Sun, Guohua Zeng, Hongxing Liu
Format: Article
Language:English
Published: BMC 2022-12-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-022-01726-w
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author Jiwang Deng
Bangxian Yu
Zhenglin Chang
Sicheng Wu
Guanlin Li
Wenzhe Chen
Shujue Li
Xiaolu Duan
Wenqi Wu
Xinyuan Sun
Guohua Zeng
Hongxing Liu
author_facet Jiwang Deng
Bangxian Yu
Zhenglin Chang
Sicheng Wu
Guanlin Li
Wenzhe Chen
Shujue Li
Xiaolu Duan
Wenqi Wu
Xinyuan Sun
Guohua Zeng
Hongxing Liu
author_sort Jiwang Deng
collection DOAJ
description Abstract Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.
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spelling doaj.art-9dce51f747784e1eb11850c513349e4b2022-12-22T03:50:37ZengBMCJournal of Nanobiotechnology1477-31552022-12-0120111710.1186/s12951-022-01726-wCerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damageJiwang Deng0Bangxian Yu1Zhenglin Chang2Sicheng Wu3Guanlin Li4Wenzhe Chen5Shujue Li6Xiaolu Duan7Wenqi Wu8Xinyuan Sun9Guohua Zeng10Hongxing Liu11Department of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Urology, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityAbstract Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.https://doi.org/10.1186/s12951-022-01726-wCerium oxide nanoparticlesOxidative stress damageOxalateReactive oxygen species
spellingShingle Jiwang Deng
Bangxian Yu
Zhenglin Chang
Sicheng Wu
Guanlin Li
Wenzhe Chen
Shujue Li
Xiaolu Duan
Wenqi Wu
Xinyuan Sun
Guohua Zeng
Hongxing Liu
Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
Journal of Nanobiotechnology
Cerium oxide nanoparticles
Oxidative stress damage
Oxalate
Reactive oxygen species
title Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
title_full Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
title_fullStr Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
title_full_unstemmed Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
title_short Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage
title_sort cerium oxide based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria induced oxidative stress damage
topic Cerium oxide nanoparticles
Oxidative stress damage
Oxalate
Reactive oxygen species
url https://doi.org/10.1186/s12951-022-01726-w
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