Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway

Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway

Xi Chen,1,2 Wang Zhouhua,1 Zhou Jie,1 Fu Xinlu,3 Liang Jinqiang,3 Qiu Yuwen,3 Huang Zhiying1,31School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Pe...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Chen X, Zhouhua W, Jie Z, Xinlu F, Jinqiang L, Yuwen Q, Zhiying H
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/ada92b58378046689455f56e83051f9a
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:ada92b58378046689455f56e83051f9a
record_format dspace
spelling oai:doaj.org-article:ada92b58378046689455f56e83051f9a2021-12-02T02:04:22ZRenal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway1178-2013https://doaj.org/article/ada92b58378046689455f56e83051f9a2014-12-01T00:00:00Zhttp://www.dovepress.com/renal-interstitial-fibrosis-induced-by-high-dose-mesoporous-silica-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Xi Chen,1,2 Wang Zhouhua,1 Zhou Jie,1 Fu Xinlu,3 Liang Jinqiang,3 Qiu Yuwen,3 Huang Zhiying1,31School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.Keywords: mesoporous silica nanoparticles (MSNs), acute kidney injury, renal interstitial fibrosis, NF-κBChen XZhouhua WJie ZXinlu FJinqiang LYuwen QZhiying HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1-22 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Chen X
Zhouhua W
Jie Z
Xinlu F
Jinqiang L
Yuwen Q
Zhiying H
Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
description Xi Chen,1,2 Wang Zhouhua,1 Zhou Jie,1 Fu Xinlu,3 Liang Jinqiang,3 Qiu Yuwen,3 Huang Zhiying1,31School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.Keywords: mesoporous silica nanoparticles (MSNs), acute kidney injury, renal interstitial fibrosis, NF-κB
format article
author Chen X
Zhouhua W
Jie Z
Xinlu F
Jinqiang L
Yuwen Q
Zhiying H
author_facet Chen X
Zhouhua W
Jie Z
Xinlu F
Jinqiang L
Yuwen Q
Zhiying H
author_sort Chen X
title Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
title_short Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
title_full Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
title_fullStr Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
title_full_unstemmed Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
title_sort renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the nf-κb signaling pathway
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/ada92b58378046689455f56e83051f9a
work_keys_str_mv AT chenx renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT zhouhuaw renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT jiez renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT xinluf renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT jinqiangl renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT yuwenq renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
AT zhiyingh renalinterstitialfibrosisinducedbyhighdosemesoporoussilicananoparticlesviathenfkappabsignalingpathway
_version_ 1718402726326435840

Ejemplares similares