The ameliorative effects of a hypnotic bromvalerylurea in sepsis

Satoshi Kikuchi, Tasuku Nishihara, Shun Kawasaki, Naoki Abe, Jun Kuwabara, Mohammed E. Choudhury, Hisaaki Takahashi, Hajime Yano, Takumi Nagaro, Yuji Watanabe, Mayuki Aibiki, Junya Tanaka

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF.

Original languageEnglish
Pages (from-to)319-326
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume459
Issue number2
DOIs
Publication statusPublished - 03-04-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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