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-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.
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan. shink@med.nagoya-cu.ac.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Kato
authors.forename: Mohamed Hamed
authors.initials: MH
authors.lastname: Hussein
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kakita
authors.forename: Tatenobu
authors.initials: T
authors.lastname: Goto
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Daoud
authors.forename: Takenori
authors.initials: T
authors.lastname: Kato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sugiura
authors.forename: Masanori
authors.initials: M
authors.lastname: Nobata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Endo
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mizuno
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Ineko
authors.initials: I
authors.lastname: Kato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: 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
chemical_list: 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