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: 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
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 32 Issue 6 Pg. 586-92 (Dec 2009) ISSN: 1540-0514 [Electronic] United States
• PMID: 19295481 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Cyclic N-Oxides
• Free Radical Scavengers
• Free Radicals
• HMGB1 Protein
• Spin Labels
• Edaravone
• Antipyrine
• tempol

Topics

• Animals
• Animals, Newborn
• Antioxidants (chemistry)
• Antipyrine (analogs & derivatives, pharmacology)
• Blood Pressure
• Body Weight
• Cyclic N-Oxides (pharmacology)
• Edaravone
• Free Radical Scavengers (pharmacology)
• Free Radicals
• HMGB1 Protein (blood)
• Heart Rate
• Inflammation
• Sepsis (physiopathology)
• Spin Labels
• Swine
• Time Factors