- 著者
-
Mayuka Yamada
Midori Suzuki
Takuya Noguchi
Takumi Yokosawa
Yuto Sekiguchi
Natsumi Mutoh
Takashi Toyama
Yusuke Hirata
Gi-Wook Hwang
Atsushi Matsuzawa
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- BPB Reports (ISSN:2434432X)
- 巻号頁・発行日
- vol.3, no.1, pp.16-21, 2020 (Released:2020-11-26)
- 参考文献数
- 27
- 被引用文献数
-
4
7
Both NF-E2-related factor 2 (Nrf2) and heat shock protein 70 (HSP70) contribute to cellular defense to various stresses, and have emerged as candidates of therapeutic targets to improve or prevent tissue damage. Cefotaxime (CTX), a third-generation cephalosporin antibiotic, is conceived as a safe drug largely free from side effects. CTX exhibits broad-spectrum antimicrobial activity, and thereby, is most commonly prescribed for the treatment of infectious diseases induced by Gram-positive or Gram-negative bacteria. In this study, we unexpectedly found the beneficial properties of CTX that upregulate both Nrf2 and HSP70 to the extent that stress-induced damage is ameliorated. Non-toxic levels of reactive oxygen species (ROS) induced by CTX activated the Nrf2 pathway without cytotoxicity, which in turn upregulated HSP70. Interestingly, the cytotoxicity of Fas/CD95 ligand (FasL), a cytotoxic cytokine that strongly induces apoptosis, was significantly ameliorated by pre-treatment with CTX, most likely because of the upregulation of Nrf2 and HSP70. Our results therefore show novel properties of CTX, which raise the possibility that CTX works as a non-toxic therapeutic agent for preventing and repairing tissue damage.