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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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3289 |
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| author | Jeongah Song Kyung-Jin Jung Mi-Jin Yang Woojin Kim Byoung-Seok Lee Seong-Kyu Choe Seong-Jin Kim Jeong-Ho Hwang |
| author_facet | Jeongah Song Kyung-Jin Jung Mi-Jin Yang Woojin Kim Byoung-Seok Lee Seong-Kyu Choe Seong-Jin Kim Jeong-Ho Hwang |
| author_sort | Jeongah Song |
| collection | DOAJ |
| 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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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:41:54Z |
| publishDate | 2022-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-eeb4bbed3fb64c3baef368963bb5be0e2023-11-24T01:36:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236328910.3390/ijms23063289Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of ExposureJeongah Song0Kyung-Jin Jung1Mi-Jin Yang2Woojin Kim3Byoung-Seok Lee4Seong-Kyu Choe5Seong-Jin Kim6Jeong-Ho Hwang7Animal Model Research Group, Korea Institute of Toxicology, Jeongeup 56212, KoreaBioanalytical and Immunoanalytical Research Group, Korea Institute of Toxicology, Daejeon 34114, KoreaJeonbuk Pathology Research Group, Korea Institute of Toxicology, Jeongeup 56212, KoreaToxicologic Pathology Research Group, Korea Institute of Toxicology, Daejeon 34114, KoreaToxicologic Pathology Research Group, Korea Institute of Toxicology, Daejeon 34114, KoreaDepartment of Microbiology, Wonkwang University School of Medicine, Iksan 54538, KoreaDepartment of Biomedical Science, Graduate School, Wonkwang University, Iksan 54538, KoreaAnimal Model Research Group, Korea Institute of Toxicology, Jeongeup 56212, KoreaPolyhexamethylene 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.https://www.mdpi.com/1422-0067/23/6/3289polyhexamethylene guanidine phosphatemembrane integrityroute of exposurelung injuryliver toxicity |
| spellingShingle | Jeongah Song Kyung-Jin Jung Mi-Jin Yang Woojin Kim Byoung-Seok Lee Seong-Kyu Choe Seong-Jin Kim Jeong-Ho Hwang Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure International Journal of Molecular Sciences polyhexamethylene guanidine phosphate membrane integrity route of exposure lung injury liver toxicity |
| 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 | polyhexamethylene guanidine phosphate membrane integrity route of exposure lung injury liver toxicity |
| url | https://www.mdpi.com/1422-0067/23/6/3289 |
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