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Assessment of acute and repeated pulmonary toxicities of oligo(2-(2-ethoxy)ethoxyethyl guanidium chloride in mice

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Abstract

Oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride (PGH) and polyhexamethyleneguanidine phosphate (PHMG-P) are cationic biocides containing a guanidine group. Direct exposure of the lungs to PHMG-P is known to induce pulmonary inflammation and fibrotic changes. Few studies have assessed the pulmonary toxicity of PGH, another member of the guanidine family. In this study, we assessed the acute and repeated toxicity of PGH and PHMG-P to compare the pathological progression induced by both chemicals. PGH (1.5 mg/kg) or PHMG (0.6 mg/kg) was instilled intratracheally to mice once or three times every 4 days; subsequently, cytokine levels were quantified and a histopathological examination was performed. To verify the toxic mechanism of PGH, we quantified cell viability and cytokine production induced by PGH or PHMG-P in the presence or absence of anionic material in cells. Instillation of PGH and PHMG-P into the mouse lung increased cytokine production, immune cell infiltration, and pulmonary fibrotic changes. These pathological changes were exacerbated over time in the single- and the repeated-dose PHMG-P groups, but were resolved over time in the PGH groups. PGH or PHMG-P showed cytotoxic effects, IL-1β secretion, and ROS production in a dose-dependent manner in human cell lines. However, the co-treatment of anionic materials with PGH or PHMG-P significantly reduced these toxic responses, which confirmed that the cation of PGH disrupted the plasma membrane via ionic interaction, as observed for PHMG-P. In addition, we suggest the disruption of plasma membrane as a molecular initiating event of cationic chemicals-induced adverse outcomes when exposed directly to the lungs.

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Acknowledgements

This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (no. 2017R1D1A1B04032833).

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Authors and Affiliations

  1. Animal Model Research Group, Korea Institute of Toxicology, Jeongeup, 56212, Republic of Korea

    Jeongah Song

  2. Bioanalytical and Immunoanalytical Research Group, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea

    Kyung Jin Jung

  3. Pathology Research Group, Korea Institute of Toxicology, Jeongeup, 56212, Republic of Korea

    Mi-jin Yang

  4. Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, 56212, Republic of Korea

    Su-Cheol Han

  5. National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup, 56212, Republic of Korea

    Kyuhong Lee

  6. Human and Environmental Toxicology, University of Science and Technology, Daejeon, 34113, Republic of Korea

    Kyuhong Lee

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  1. Jeongah Song
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Correspondence to Jeongah Song or Kyuhong Lee.

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Song, J., Jung, K.J., Yang, Mj. et al. Assessment of acute and repeated pulmonary toxicities of oligo(2-(2-ethoxy)ethoxyethyl guanidium chloride in mice. Toxicol Res. 37, 99–113 (2021). https://doi.org/10.1007/s43188-020-00058-x

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  • DOI: https://doi.org/10.1007/s43188-020-00058-x

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