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Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models

BACKGROUND: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death fol...

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Autores principales: Gupta, Sandeep, Li, Shunan, Abedin, Md. Joynal, Noppakun, Kajohnsak, Wang, Lawrence, Kaur, Tarundeep, Najafian, Behzad, Rodrigues, Cecília M. P., Steer, Clifford J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494686/
https://www.ncbi.nlm.nih.gov/pubmed/23152827
http://dx.doi.org/10.1371/journal.pone.0048950
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author Gupta, Sandeep
Li, Shunan
Abedin, Md. Joynal
Noppakun, Kajohnsak
Wang, Lawrence
Kaur, Tarundeep
Najafian, Behzad
Rodrigues, Cecília M. P.
Steer, Clifford J.
author_facet Gupta, Sandeep
Li, Shunan
Abedin, Md. Joynal
Noppakun, Kajohnsak
Wang, Lawrence
Kaur, Tarundeep
Najafian, Behzad
Rodrigues, Cecília M. P.
Steer, Clifford J.
author_sort Gupta, Sandeep
collection PubMed
description BACKGROUND: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. METHODOLOGY/PRINCIPAL FINDINGS: We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. CONCLUSIONS: This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies.
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spelling pubmed-34946862012-11-14 Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models Gupta, Sandeep Li, Shunan Abedin, Md. Joynal Noppakun, Kajohnsak Wang, Lawrence Kaur, Tarundeep Najafian, Behzad Rodrigues, Cecília M. P. Steer, Clifford J. PLoS One Research Article BACKGROUND: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. METHODOLOGY/PRINCIPAL FINDINGS: We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. CONCLUSIONS: This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies. Public Library of Science 2012-11-09 /pmc/articles/PMC3494686/ /pubmed/23152827 http://dx.doi.org/10.1371/journal.pone.0048950 Text en © 2012 Gupta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gupta, Sandeep
Li, Shunan
Abedin, Md. Joynal
Noppakun, Kajohnsak
Wang, Lawrence
Kaur, Tarundeep
Najafian, Behzad
Rodrigues, Cecília M. P.
Steer, Clifford J.
Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title_full Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title_fullStr Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title_full_unstemmed Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title_short Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
title_sort prevention of acute kidney injury by tauroursodeoxycholic acid in rat and cell culture models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494686/
https://www.ncbi.nlm.nih.gov/pubmed/23152827
http://dx.doi.org/10.1371/journal.pone.0048950
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