| RRC ID |
78233
|
| 著者 |
Ishihara T, Tanaka KI, Takafuji A, Miura K, Mizushima T.
|
| タイトル |
Attenuation of LPS-Induced Lung Injury by Benziodarone via Reactive Oxygen Species Reduction.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
As overproduction of reactive oxygen species (ROS) causes various diseases, antioxidants that scavenge ROS, or inhibitors that suppress excessive ROS generation, can be used as therapeutic agents. From a library of approved drugs, we screened compounds that reduced superoxide anions produced by pyocyanin-stimulated leukemia cells and identified benzbromarone. Further investigation of several of its analogues showed that benziodarone possessed the highest activity in reducing superoxide anions without causing cytotoxicity. In contrast, in a cell-free assay, benziodarone induced only a minimal decrease in superoxide anion levels generated by xanthine oxidase. These results suggest that benziodarone is an inhibitor of NADPH oxidases in the plasma membrane but is not a superoxide anion scavenger. We investigated the preventive effect of benziodarone on lipopolysaccharide (LPS)-induced murine lung injury as a model of acute respiratory distress syndrome (ARDS). Intratracheal administration of benziodarone attenuated tissue damage and inflammation via its ROS-reducing activity. These results indicate the potential application of benziodarone as a therapeutic agent against diseases caused by ROS overproduction.
|
| 巻・号 |
24(12)
|
| 公開日 |
2023-6-12
|
| DOI |
10.3390/ijms241210035
|
| PII |
ijms241210035
|
| PMID |
37373184
|
| PMC |
PMC10298550
|
| MeSH |
Animals
Humans
Lipopolysaccharides / toxicity
Lung Injury*
Mice
NADPH Oxidases / metabolism
Reactive Oxygen Species / metabolism
Superoxides
|
| リソース情報 |
| ヒト・動物細胞 |
U-937 DE-4(RCB0435)
HL-60(RCB3683) |
