Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Toxicologic pathological mechanism of acute lung injury induced by oral administration of benzalkonium chloride in mice

  • Hidehisa Sekijima (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Toru Oshima (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Yuno Ueji (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Naoko Kuno (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Yukino Kondo (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Saera Nomura (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Tomomi Asakura (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine) ;
  • Kae Sakai‑Sugino (Department of Food and Nutrition, Tsu City College) ;
  • Mitsuo Kawano (Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine) ;
  • Hiroshi Komada (Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine) ;
  • Hirokazu Kotani (Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine)
  • Received : 2022.12.18
  • Accepted : 2023.03.23
  • Published : 2023.07.15
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Abstract

Benzalkonium chloride (BAC) intoxication causes fatal lung injuries, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the pathogenesis of ALI/ARDS induced by BAC ingestion is poorly understood. This study aimed to clarify the mechanism of lung toxicity after BAC ingestion in a mouse model. BAC was orally administered to C57BL/6 mice at doses of 100, 250, and 1250 mg/kg. After administration, BAC concentrations in the blood and lungs were evaluated via liquid chromatography with tandem mass spectrometry. Lung tissue injury was evaluated via histological and protein analyses. Blood and lung BAC concentration levels after oral administration increased in a dose-dependent manner, with the concentrations directly proportional to the dose administered. The severity of lung injury worsened over time after the oral administration of 1250 mg/kg BAC. An increase in the terminal transferase dUTP nick end labeling-positive cells and cleaved caspase-3 levels was observed in the lungs after 1250 mg/kg BAC administration. In addition, increased cleaved caspase-9 levels and mitochondrial cytochrome c release into the cytosol were observed. These results suggest that lung tissue injury with excessive apoptosis contributes to BAC-induced ALI development and exacerbation. Our findings provide useful information for developing an effective treatment for ALI/ARDS induced by BAC ingestion.

Keywords

Acknowledgement

We thank Tomomi Kurata, Misako Tanno, Akiko Hara, and Yoko Mukai for providing technical assistance. We would like to thank Editage (www.editage.com) for English language editing.

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