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Attenuation of LPS-Induced Lung Injury by Benziodarone via Reactive Oxygen Species Reduction

Tsutomu Ishihara1, Ken-Ichiro Tanaka2, Ayaka Takafuji2

  • 1Department of Chemical Biology and Applied Chemistry, College of Engineering, Nihon University, Fukushima 9638642, Japan.

International Journal of Molecular Sciences
|June 28, 2023
PubMed

Insights

Benziodarone effectively reduces superoxide anions, a key factor in diseases, by inhibiting NADPH oxidases. This compound shows therapeutic potential for treating acute respiratory distress syndrome and other ROS-related conditions.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cell Biology

Background:

  • Overproduction of reactive oxygen species (ROS) is implicated in various diseases.
  • Antioxidants and ROS inhibitors are potential therapeutic agents.
  • Approved drugs were screened for ROS-scavenging or inhibitory activity.

Purpose of the Study:

  • To identify compounds that reduce superoxide anion production in leukemia cells.
  • To investigate the mechanism of action of identified compounds.
  • To evaluate the therapeutic potential of benziodarone in a model of acute respiratory distress syndrome (ARDS).

Main Methods:

  • Screening of approved drugs for inhibition of pyocyanin-stimulated superoxide anion production in leukemia cells.
  • Assessing cytotoxicity of identified compounds.
  • Evaluating the effect of benziodarone on superoxide anion levels in a cell-free xanthine oxidase assay.
  • Investigating the preventive effect of benziodarone on lipopolysaccharide (LPS)-induced murine lung injury.

Main Results:

  • Benzbromarone was identified as a compound that reduced superoxide anions.
  • Benziodarone, an analogue of benzbromarone, showed higher activity in reducing superoxide anions without cytotoxicity.
  • Benziodarone acts as an inhibitor of plasma membrane NADPH oxidases, not a direct superoxide scavenger.
  • Intratracheal administration of benziodarone attenuated LPS-induced lung injury and inflammation.

Conclusions:

  • Benziodarone is a potent inhibitor of NADPH oxidases.
  • Benziodarone demonstrates therapeutic potential for ROS-related diseases, including ARDS.
  • Further investigation into benziodarone as a therapeutic agent is warranted.
Keywords:
ARDSROSbenzbromaronebenziodaronesuperoxide anions

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