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Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress

Polyhexamethyleneguanidine phosphate (PHMG-P) is a widely used polymeric antimicrobial agent known to induce significant pulmonary toxicity. Several studies have reported that the liver also can be a target organ of polyhexamethyleneguanidine (PHMG) toxicity, but the exact effect of this compound on...

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Autores principales: Kim, Sou Hyun, Kwon, Doyoung, Lee, Seunghyun, Ki, Sung Hwan, Jeong, Hye Gwang, Hong, Jin Tae, Lee, Yun-Hee, Jung, Young-Suk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770470/
https://www.ncbi.nlm.nih.gov/pubmed/31484321
http://dx.doi.org/10.3390/cells8091023
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author Kim, Sou Hyun
Kwon, Doyoung
Lee, Seunghyun
Ki, Sung Hwan
Jeong, Hye Gwang
Hong, Jin Tae
Lee, Yun-Hee
Jung, Young-Suk
author_facet Kim, Sou Hyun
Kwon, Doyoung
Lee, Seunghyun
Ki, Sung Hwan
Jeong, Hye Gwang
Hong, Jin Tae
Lee, Yun-Hee
Jung, Young-Suk
author_sort Kim, Sou Hyun
collection PubMed
description Polyhexamethyleneguanidine phosphate (PHMG-P) is a widely used polymeric antimicrobial agent known to induce significant pulmonary toxicity. Several studies have reported that the liver also can be a target organ of polyhexamethyleneguanidine (PHMG) toxicity, but the exact effect of this compound on liver cells is not well understood. To identify the mechanism of PHMG hepatotoxicity, HepG2 cells were exposed to PHMG-P for 72 h. The cell viability was significantly decreased by PHMG-P in a time- and concentration-dependent manner. The mitochondrial membrane potential was markedly reduced by PHMG-P and the apoptotic signaling cascade was activated. The increases observed in C/EBP homologous protein (CHOP), p-IRE, and p-JNK levels in PHMG-P-treated cells indicated the induction of endoplasmic reticulum stress. To verify the role of ER stress in PHMG-P-induced cytotoxicity, HepG2 cells were pretreated with the chemical chaperone, tauroursodeoxycholic acid (TUDCA) and then co-treated with TUDCA and PHMG-P for 24 h. Interestingly, TUDCA inhibited PHMG-P-induced ER stress and cytotoxicity in a dose-dependent manner. The apoptotic cell death and mitochondrial depolarization were also prevented by TUDCA. The proteins involved in the apoptotic pathway were all normalized to their control levels in TUDCA-treated cells. In conclusion, the results suggest that PHMG-P induced significant cytotoxicity in liver cells and ER stress-mediated apoptosis, which may be an important mechanism mediating this hepatotoxicity.
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spelling pubmed-67704702019-10-30 Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress Kim, Sou Hyun Kwon, Doyoung Lee, Seunghyun Ki, Sung Hwan Jeong, Hye Gwang Hong, Jin Tae Lee, Yun-Hee Jung, Young-Suk Cells Article Polyhexamethyleneguanidine phosphate (PHMG-P) is a widely used polymeric antimicrobial agent known to induce significant pulmonary toxicity. Several studies have reported that the liver also can be a target organ of polyhexamethyleneguanidine (PHMG) toxicity, but the exact effect of this compound on liver cells is not well understood. To identify the mechanism of PHMG hepatotoxicity, HepG2 cells were exposed to PHMG-P for 72 h. The cell viability was significantly decreased by PHMG-P in a time- and concentration-dependent manner. The mitochondrial membrane potential was markedly reduced by PHMG-P and the apoptotic signaling cascade was activated. The increases observed in C/EBP homologous protein (CHOP), p-IRE, and p-JNK levels in PHMG-P-treated cells indicated the induction of endoplasmic reticulum stress. To verify the role of ER stress in PHMG-P-induced cytotoxicity, HepG2 cells were pretreated with the chemical chaperone, tauroursodeoxycholic acid (TUDCA) and then co-treated with TUDCA and PHMG-P for 24 h. Interestingly, TUDCA inhibited PHMG-P-induced ER stress and cytotoxicity in a dose-dependent manner. The apoptotic cell death and mitochondrial depolarization were also prevented by TUDCA. The proteins involved in the apoptotic pathway were all normalized to their control levels in TUDCA-treated cells. In conclusion, the results suggest that PHMG-P induced significant cytotoxicity in liver cells and ER stress-mediated apoptosis, which may be an important mechanism mediating this hepatotoxicity. MDPI 2019-09-03 /pmc/articles/PMC6770470/ /pubmed/31484321 http://dx.doi.org/10.3390/cells8091023 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Sou Hyun
Kwon, Doyoung
Lee, Seunghyun
Ki, Sung Hwan
Jeong, Hye Gwang
Hong, Jin Tae
Lee, Yun-Hee
Jung, Young-Suk
Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title_full Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title_fullStr Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title_full_unstemmed Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title_short Polyhexamethyleneguanidine Phosphate-Induced Cytotoxicity in Liver Cells Is Alleviated by Tauroursodeoxycholic Acid (TUDCA) via a Reduction in Endoplasmic Reticulum Stress
title_sort polyhexamethyleneguanidine phosphate-induced cytotoxicity in liver cells is alleviated by tauroursodeoxycholic acid (tudca) via a reduction in endoplasmic reticulum stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770470/
https://www.ncbi.nlm.nih.gov/pubmed/31484321
http://dx.doi.org/10.3390/cells8091023
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