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.

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.

• Authors: 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
• Journal: Pediatric research (Pediatr Res) Vol. 72 Issue 6 Pg. 600-5 (Dec 2012) ISSN: 1530-0447 [Electronic] United States
• PMID: 23041664 (Publication Type: Journal Article)

Chemical References

• ETR-p1-f1 antisense peptide
• Endothelin Receptor Antagonists
• Intercellular Signaling Peptides and Proteins
• Interleukin-6
• Peptides
• Creatinine
• Hydrogen Peroxide
• Aspartate Aminotransferases

Topics

• Animals
• Aspartate Aminotransferases (blood)
• Creatinine (blood)
• Endothelin Receptor Antagonists
• Hydrogen Peroxide (metabolism)
• Intercellular Signaling Peptides and Proteins
• Interleukin-6 (metabolism)
• Oxidative Stress (drug effects)
• Peptides (pharmacology)
• Swine