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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)586-592
Number of pages7
JournalShock
Volume32
Issue number6
DOIs
Publication statusPublished - 01-12-2009

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Free Radical Scavengers
Ligation
Arterial Pressure
Nitrites
Cardiac Output
Nitrates
Hydrogen Peroxide
Free Radicals
Neonatal Sepsis
phenylmethylpyrazolone
Heart Rate
Sepsis
Antioxidants
Gases

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Kato, Shin ; Hussein, Mohamed Hamed ; Kakita, Hiroki ; Goto, Tatenobu ; Daoud, Ghada A. ; Kato, Takenori ; Sugiura, Takahiro ; Nobata, Masanori ; Nakajima, Yoko ; Endo, Takeshi ; Mizuno, Keisuke ; Ito, Tetsuya ; Kato, Ineko ; Suzuki, Satoshi ; Togari, Hajime. / Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model. In: Shock. 2009 ; Vol. 32, No. 6. pp. 586-592.
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title = "Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model",
abstract = "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.",
author = "Shin Kato and Hussein, {Mohamed Hamed} and Hiroki Kakita and Tatenobu Goto and Daoud, {Ghada A.} and Takenori Kato and Takahiro Sugiura and Masanori Nobata and Yoko Nakajima and Takeshi Endo and Keisuke Mizuno and Tetsuya Ito and Ineko Kato and Satoshi Suzuki and Hajime Togari",
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Kato, S, Hussein, MH, Kakita, H, Goto, T, Daoud, GA, Kato, T, Sugiura, T, Nobata, M, Nakajima, Y, Endo, T, Mizuno, K, Ito, T, Kato, I, Suzuki, S & Togari, H 2009, 'Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model', Shock, vol. 32, no. 6, pp. 586-592. https://doi.org/10.1097/SHK.0b013e3181a2b886

Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model. / Kato, Shin; Hussein, Mohamed Hamed; Kakita, Hiroki; Goto, Tatenobu; Daoud, Ghada A.; Kato, Takenori; Sugiura, Takahiro; Nobata, Masanori; Nakajima, Yoko; Endo, Takeshi; Mizuno, Keisuke; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Togari, Hajime.

In: Shock, Vol. 32, No. 6, 01.12.2009, p. 586-592.

Research output: Contribution to journalArticle

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T1 - Edaravone, a novel free radical scavenger, reduces high-mobility group bOX 1 and prolongs survival in a neonatal sepsis model

AU - Kato, Shin

AU - Hussein, Mohamed Hamed

AU - Kakita, Hiroki

AU - Goto, Tatenobu

AU - Daoud, Ghada A.

AU - Kato, Takenori

AU - Sugiura, Takahiro

AU - Nobata, Masanori

AU - Nakajima, Yoko

AU - Endo, Takeshi

AU - Mizuno, Keisuke

AU - Ito, Tetsuya

AU - Kato, Ineko

AU - Suzuki, Satoshi

AU - Togari, Hajime

PY - 2009/12/1

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N2 - 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.

AB - 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.

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