The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model

Xiao Qi Xie, Yotaro Shinozawa, Junichi Sasaki, Kiyotsugu Takuma, Satoshi Akaishi, Satoshi Yamanouchi, Tomoyuki Endo, Ryosuke Nomura, Michio Kobayashi, Daisuke Kudo, Nobuko Hojo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.

Original languageEnglish
Pages (from-to)298-303
Number of pages6
JournalJournal of Surgical Research
Volume146
Issue number2
DOIs
Publication statusPublished - 2008 May 15
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Punctures
Ligation
Arginine
Sepsis
Nitric Oxide
Heme Oxygenase-1
17-Hydroxycorticosteroids
Urine
Lung
Liver
Nitrites
Nitrates
Epinephrine
Dopamine
Norepinephrine
Oxidative Stress
Survival Rate
Survival

Keywords

  • arginine
  • heme oxygenase
  • neuroendocrine system
  • nitric oxide
  • nitric oxide synthase inhibitor
  • sepsis

ASJC Scopus subject areas

  • Surgery

Cite this

The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model. / Xie, Xiao Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko.

In: Journal of Surgical Research, Vol. 146, No. 2, 15.05.2008, p. 298-303.

Research output: Contribution to journalArticle

Xie, XQ, Shinozawa, Y, Sasaki, J, Takuma, K, Akaishi, S, Yamanouchi, S, Endo, T, Nomura, R, Kobayashi, M, Kudo, D & Hojo, N 2008, 'The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model', Journal of Surgical Research, vol. 146, no. 2, pp. 298-303. https://doi.org/10.1016/j.jss.2007.07.016
Xie, Xiao Qi ; Shinozawa, Yotaro ; Sasaki, Junichi ; Takuma, Kiyotsugu ; Akaishi, Satoshi ; Yamanouchi, Satoshi ; Endo, Tomoyuki ; Nomura, Ryosuke ; Kobayashi, Michio ; Kudo, Daisuke ; Hojo, Nobuko. / The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model. In: Journal of Surgical Research. 2008 ; Vol. 146, No. 2. pp. 298-303.
@article{d4000a443fd54e4db7b5bb0ea25a46af,
title = "The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model",
abstract = "Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.",
keywords = "arginine, heme oxygenase, neuroendocrine system, nitric oxide, nitric oxide synthase inhibitor, sepsis",
author = "Xie, {Xiao Qi} and Yotaro Shinozawa and Junichi Sasaki and Kiyotsugu Takuma and Satoshi Akaishi and Satoshi Yamanouchi and Tomoyuki Endo and Ryosuke Nomura and Michio Kobayashi and Daisuke Kudo and Nobuko Hojo",
year = "2008",
month = "5",
day = "15",
doi = "10.1016/j.jss.2007.07.016",
language = "English",
volume = "146",
pages = "298--303",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - The Effects of Arginine and Selective Inducible Nitric Oxide Synthase Inhibitor on Pathophysiology of Sepsis in a CLP Model

AU - Xie, Xiao Qi

AU - Shinozawa, Yotaro

AU - Sasaki, Junichi

AU - Takuma, Kiyotsugu

AU - Akaishi, Satoshi

AU - Yamanouchi, Satoshi

AU - Endo, Tomoyuki

AU - Nomura, Ryosuke

AU - Kobayashi, Michio

AU - Kudo, Daisuke

AU - Hojo, Nobuko

PY - 2008/5/15

Y1 - 2008/5/15

N2 - Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.

AB - Background: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.

KW - arginine

KW - heme oxygenase

KW - neuroendocrine system

KW - nitric oxide

KW - nitric oxide synthase inhibitor

KW - sepsis

UR - http://www.scopus.com/inward/record.url?scp=41649111282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41649111282&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2007.07.016

DO - 10.1016/j.jss.2007.07.016

M3 - Article

C2 - 17997414

AN - SCOPUS:41649111282

VL - 146

SP - 298

EP - 303

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -