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Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure

Polyhexamethylene guanidine phosphate (PHMG-P), a cationic biocide, is widely used in household products due to its strong bactericidal activity and low toxicity. However, it causes fatal lung damage when inhaled. In this study, we investigated why PHMG-P causes fatal lung injury when inhaled, and d...

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Autores principales: Song, Jeongah, Jung, Kyung-Jin, Yang, Mi-Jin, Kim, Woojin, Lee, Byoung-Seok, Choe, Seong-Kyu, Kim, Seong-Jin, Hwang, Jeong-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955148/
https://www.ncbi.nlm.nih.gov/pubmed/35328708
http://dx.doi.org/10.3390/ijms23063289
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author Song, Jeongah
Jung, Kyung-Jin
Yang, Mi-Jin
Kim, Woojin
Lee, Byoung-Seok
Choe, Seong-Kyu
Kim, Seong-Jin
Hwang, Jeong-Ho
author_facet Song, Jeongah
Jung, Kyung-Jin
Yang, Mi-Jin
Kim, Woojin
Lee, Byoung-Seok
Choe, Seong-Kyu
Kim, Seong-Jin
Hwang, Jeong-Ho
author_sort Song, Jeongah
collection PubMed
description Polyhexamethylene guanidine phosphate (PHMG-P), a cationic biocide, is widely used in household products due to its strong bactericidal activity and low toxicity. However, it causes fatal lung damage when inhaled. In this study, we investigated why PHMG-P causes fatal lung injury when inhaled, and demonstrated that the disruption of membrane integrity through ionic interaction—a molecular initiating event of PHMG-P—determines toxicity. Mice were injected intravenously with 0.9 or 7.2 mg/kg PHMG-P (IV group), or instilled intratracheally with 0.9 mg/kg PHMG-P (ITI group); they were euthanatized at 4 h and on days 1 and 7 after treatment. Increased total BAL cell count and proinflammatory cytokine production, along with fibrotic changes in the lungs, were detected in the ITI group only. Levels of hepatic enzymes and hepatic serum amyloid A mRNA expression were markedly upregulated in the 7.2 mg/kg IV and ITI groups at 4 h or day 1 after treatment, but returned to baseline. No pathological findings were detected in the heart, liver, or kidneys. To simulate the IV injection, A549, THP-1, and HepG2 cells were treated with PHMG-P in cell culture media supplemented with different serum concentrations. Increased serum concentration was associated with an increase in cell viability. These results support the idea that direct contact between PHMG-P and cell membranes is necessary for PHMG-induced toxicity.
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spelling pubmed-89551482022-03-26 Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure Song, Jeongah Jung, Kyung-Jin Yang, Mi-Jin Kim, Woojin Lee, Byoung-Seok Choe, Seong-Kyu Kim, Seong-Jin Hwang, Jeong-Ho Int J Mol Sci Article Polyhexamethylene guanidine phosphate (PHMG-P), a cationic biocide, is widely used in household products due to its strong bactericidal activity and low toxicity. However, it causes fatal lung damage when inhaled. In this study, we investigated why PHMG-P causes fatal lung injury when inhaled, and demonstrated that the disruption of membrane integrity through ionic interaction—a molecular initiating event of PHMG-P—determines toxicity. Mice were injected intravenously with 0.9 or 7.2 mg/kg PHMG-P (IV group), or instilled intratracheally with 0.9 mg/kg PHMG-P (ITI group); they were euthanatized at 4 h and on days 1 and 7 after treatment. Increased total BAL cell count and proinflammatory cytokine production, along with fibrotic changes in the lungs, were detected in the ITI group only. Levels of hepatic enzymes and hepatic serum amyloid A mRNA expression were markedly upregulated in the 7.2 mg/kg IV and ITI groups at 4 h or day 1 after treatment, but returned to baseline. No pathological findings were detected in the heart, liver, or kidneys. To simulate the IV injection, A549, THP-1, and HepG2 cells were treated with PHMG-P in cell culture media supplemented with different serum concentrations. Increased serum concentration was associated with an increase in cell viability. These results support the idea that direct contact between PHMG-P and cell membranes is necessary for PHMG-induced toxicity. MDPI 2022-03-18 /pmc/articles/PMC8955148/ /pubmed/35328708 http://dx.doi.org/10.3390/ijms23063289 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Song, Jeongah
Jung, Kyung-Jin
Yang, Mi-Jin
Kim, Woojin
Lee, Byoung-Seok
Choe, Seong-Kyu
Kim, Seong-Jin
Hwang, Jeong-Ho
Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title_full Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title_fullStr Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title_full_unstemmed Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title_short Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure
title_sort disruption of membrane integrity as a molecular initiating event determines the toxicity of polyhexamethylene guanidine phosphate depending on the routes of exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955148/
https://www.ncbi.nlm.nih.gov/pubmed/35328708
http://dx.doi.org/10.3390/ijms23063289
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