title: Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.
abstract: BACKGROUND
  Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model.
  
  
  METHODS
  A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP.
  
  
  RESULTS
  CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group.
  
  
  CONCLUSIONS
  ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tatenobu
authors.initials: T
authors.lastname: Goto
authors.forename: Mohamed Hamed
authors.initials: MH
authors.lastname: Hussein
authors.forename: Shin
authors.initials: S
authors.lastname: Kato
authors.forename: Ghada Abdel-Hamid
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: Hiroki
authors.initials: H
authors.lastname: Kakita
authors.forename: Masanori
authors.initials: M
authors.lastname: Nobata
authors.forename: Michi
authors.initials: M
authors.lastname: Kamei
authors.forename: Haruo
authors.initials: H
authors.lastname: Mizuno
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
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: Noriko
authors.initials: N
authors.lastname: Okada
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D065128:Endothelin Receptor Antagonists; D006861:Hydrogen Peroxide / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D013552:Swine
chemical_list: C109027:ETR-p1-f1 antisense peptide; D065128:Endothelin Receptor Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D010455:Peptides; D003404:Creatinine; D006861:Hydrogen Peroxide; D001219:Aspartate Aminotransferases