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Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models

Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gen...

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Autores principales: Cui, Jing, Bai, Xue-Yuan, Sun, Xuefeng, Cai, Guangyan, Hong, Quan, Ding, Rui, Chen, Xiangmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459224/
https://www.ncbi.nlm.nih.gov/pubmed/26052900
http://dx.doi.org/10.1038/srep11256
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author Cui, Jing
Bai, Xue-Yuan
Sun, Xuefeng
Cai, Guangyan
Hong, Quan
Ding, Rui
Chen, Xiangmei
author_facet Cui, Jing
Bai, Xue-Yuan
Sun, Xuefeng
Cai, Guangyan
Hong, Quan
Ding, Rui
Chen, Xiangmei
author_sort Cui, Jing
collection PubMed
description Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy.
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spelling pubmed-44592242015-06-17 Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models Cui, Jing Bai, Xue-Yuan Sun, Xuefeng Cai, Guangyan Hong, Quan Ding, Rui Chen, Xiangmei Sci Rep Article Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy. Nature Publishing Group 2015-06-08 /pmc/articles/PMC4459224/ /pubmed/26052900 http://dx.doi.org/10.1038/srep11256 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cui, Jing
Bai, Xue-Yuan
Sun, Xuefeng
Cai, Guangyan
Hong, Quan
Ding, Rui
Chen, Xiangmei
Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title_full Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title_fullStr Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title_full_unstemmed Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title_short Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
title_sort rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459224/
https://www.ncbi.nlm.nih.gov/pubmed/26052900
http://dx.doi.org/10.1038/srep11256
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