Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model

Shin Kato, Mohamed Hamed Hussein, Hiroki Kakita, Tatenobu Goto, Ghada A. Daoud, Takenori Kato, Takahiro Sugiura, Masanori Nobata, Yoko Nakajima, Takeshi Endo, Keisuke Mizuno, Tetsuya Ito, Ineko Kato, Satoshi Suzuki, Hajime Togari

研究成果: Article査読

26 被引用数 (Scopus)

抄録

Free radicals play an important role in the inflammatory process of sepsis. We hypothesized that edaravone, a novel free radical scavenger, can suppress pathophysiological events and prolong survival in a neonatal sepsis cecal ligation and perforation (CLP) model. Of 32 3-day-old anesthetized and mechanically ventilated piglets, 11 received CLP only, 10 received CLP and edaravone treatment starting 30 min after CLP, and 11 constituted a sham (control) group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, serum total hydroperoxide, nitrite and nitrate, TNF-α, and high-mobility group box 1 (HMGB1) were measured before CLP and at 1, 3, and 6 h after CLP. Compared with the CLP group, the edaravone group showed higher MAP at 6 h, lower heart rate at 1 and 3 h, lower total hydroperoxide at 1 h, lower nitrite and nitrate at 3 and 6 h, and higher (although not significantly so) mean cardiac output at 1, 3, and 6 h. TNF-α elevation was delayed from 1 h in the CLP group to 3 h in the edaravone group. In the edaravone group, HMGB1 did not change significantly at any time, whereas in the CLP group, it increased at 6 h. Survival times were longer in the edaravone group than in the CLP group (15.4 ± 1.4 vs. 10.2 ± 1 h; P < 0.005). In addition, each of the serial dilutions of edaravone had a higher biological antioxidant potential than tempol does. In conclusion, edaravone suppressed free radicals, delayed the TNF-α surge, and prevented HMGB1 elevation, thereby maintaining MAP and prolonging survival time in a neonatal sepsis CLP model.

本文言語English
ページ(範囲)586-592
ページ数7
ジャーナルShock
32
6
DOI
出版ステータスPublished - 01-12-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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