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 journalArticle

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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.

Original languageEnglish
Pages (from-to)600-605
Number of pages6
JournalPediatric Research
Volume72
Issue number6
DOIs
Publication statusPublished - 01-12-2012

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Hydrogen Peroxide
Oxidative Stress
Interleukin-6
Aspartate Aminotransferases
Antioxidants
Serum
Peptide Receptors
Oxidants
Ligation
Shock
Creatinine
Sepsis
Neonatal Sepsis
Endothelin Receptor Antagonists

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Goto, T., Hussein, M. H., Kato, S., Daoud, G. A. H., Kato, T., Sugiura, T., ... Okada, H. (2012). Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model. Pediatric Research, 72(6), 600-605. https://doi.org/10.1038/pr.2012.134
Goto, Tatenobu ; Hussein, Mohamed Hamed ; Kato, Shin ; Daoud, Ghada Abdel Hamid ; Kato, Takenori ; Sugiura, Takahiro ; Kakita, Hiroki ; Nobata, Masanori ; Kamei, Michi ; Mizuno, Haruo ; Imai, Masaki ; Ito, Tetsuya ; Kato, Ineko ; Suzuki, Satoshi ; Okada, Noriko ; Togari, Hajime ; Okada, Hidechika. / Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model. In: Pediatric Research. 2012 ; Vol. 72, No. 6. pp. 600-605.
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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.",
author = "Tatenobu Goto and Hussein, {Mohamed Hamed} and Shin Kato and Daoud, {Ghada Abdel Hamid} and Takenori Kato and Takahiro Sugiura and Hiroki Kakita and Masanori Nobata and Michi Kamei and Haruo Mizuno and Masaki Imai and Tetsuya Ito and Ineko Kato and Satoshi Suzuki and Noriko Okada and Hajime Togari and Hidechika Okada",
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Goto, T, Hussein, MH, Kato, S, Daoud, GAH, Kato, T, Sugiura, T, Kakita, H, Nobata, M, Kamei, M, Mizuno, H, Imai, M, Ito, T, Kato, I, Suzuki, S, Okada, N, Togari, H & Okada, H 2012, 'Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model', Pediatric Research, vol. 72, no. 6, pp. 600-605. https://doi.org/10.1038/pr.2012.134

Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model. / Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel Hamid; Kato, Takenori; Sugiura, Takahiro; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika.

In: Pediatric Research, Vol. 72, No. 6, 01.12.2012, p. 600-605.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model

AU - Goto, Tatenobu

AU - Hussein, Mohamed Hamed

AU - Kato, Shin

AU - Daoud, Ghada Abdel Hamid

AU - Kato, Takenori

AU - Sugiura, Takahiro

AU - Kakita, Hiroki

AU - Nobata, Masanori

AU - Kamei, Michi

AU - Mizuno, Haruo

AU - Imai, Masaki

AU - Ito, Tetsuya

AU - Kato, Ineko

AU - Suzuki, Satoshi

AU - Okada, Noriko

AU - Togari, Hajime

AU - Okada, Hidechika

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/pr.2012.134

DO - 10.1038/pr.2012.134

M3 - Article

C2 - 23041664

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VL - 72

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JF - Pediatric Research

SN - 0031-3998

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