Edaravone, a novel free radical scavenger, reduces high-mobility group box 1 and prolongs survival in a neonatal sepsis model.
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-alpha, 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-alpha 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-alpha surge, and prevented HMGB1 elevation, thereby maintaining MAP and prolonging survival time in a neonatal sepsis CLP model.
Kato
Shin
S
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan. shink@med.nagoya-cu.ac.jp
Hussein
Mohamed Hamed
MH
Kakita
Hiroki
H
Goto
Tatenobu
T
Daoud
Ghada A
GA
Kato
Takenori
T
Sugiura
Takahiro
T
Nobata
Masanori
M
Nakajima
Yoko
Y
Endo
Takeshi
T
Mizuno
Keisuke
K
Ito
Tetsuya
T
Kato
Ineko
I
Suzuki
Satoshi
S
Togari
Hajime
H
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000737:chemistry; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D003497:Cyclic N-Oxides / Q000494:pharmacology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D024243:HMGB1 Protein / Q000097:blood*; D006339:Heart Rate; D007249:Inflammation; D018805:Sepsis / Q000503:physiopathology*; D013113:Spin Labels; D013552:Swine; D013997:Time Factors
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D024243:HMGB1 Protein; D013113:Spin Labels; D000077553:Edaravone; D000983:Antipyrine; C001803:tempol