Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model

Tatenobu Goto, Mohamed Hamed Hussein, Shin Kato, Ghada Abdel Hamid Daoud, Takenori Kato, Takahiro Sugiura, Hiroki Kakita, Masanori Nobata, Michi Kamei, Haruo Mizuno, Masaki Imai, Tetsuya Ito, Ineko Kato, Satoshi Suzuki, Noriko Okada, Hajime Togari, Hidechika Okada

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.Conclusion: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.

Original languageEnglish
Pages (from-to)600-605
Number of pages6
JournalPediatric Research
Issue number6
Publication statusPublished - 12-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health


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