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Alanine-Glutamine Dipeptide (AGD) Inhibits Expression of Inflammation-Related Genes in Hemorrhagic Shock
Rongjie Yang, MD*,
Xiaoyu Tan, MD ,
Ann M. Thomas, BS*,
Robert Steppacher, MD*,
Nilofer Qureshi, PhD ,
David C. Morrison, PhD* and
Charles W. Van Way, III, MD*
From the * Department of Surgery and the
Shock/Trauma Research Center, University of
Missouri–Kansas City, Kansas City, Missouri
Correspondence: Charles W. Van Way III, MD, Professor and Chair of Surgery,
Director of Shock/Trauma Research Center, University of Missouri–Kansas
City School of Medicine, 2411 Holmes Street, Kansas City, MO 64108. Electronic
mail may be sent to
charles.vanway{at}tmcmed.org.
Background: Inflammatory factors play an important role in the
production of cellular damage after shock and reperfusion. Glutamine has been
used to modulate the inflammatory response. Alanine-glutamine dipeptide (AGD)
is a glutamine source. The hypothesis of the present study is that AGD given
during resuscitation will suppress postshock expression of messenger
ribonucleic acid (mRNA) for tumor necrosis factor (TNF- ), interleukin-1
(IL-1β) and inducible nitric oxide synthase (iNOS). Methods:
Male Sprague-Dawley rats (n = 74, 350 g ± 30 g) were randomly assigned
to 5 groups. Under isoflurane anesthesia, the femoral artery and vein were
cannulated. Hemorrhagic shock was induced by withdrawing blood through the
arterial cannula until the mean arterial pressure (MAP) was 25–30 mm Hg
and maintained at the level for 30 minutes with further withdrawals.
Resuscitation was carried out by giving 21 mL/kg Ringer's lactate (LR) with or
without the administration of AGD (936 mg/kg) and returning the shed blood.
Controls were normal (anesthesia only), sham (surgical preparation), and shock
(preparation and shock). Rats (n = 45, 9 per group) were killed 30 minutes
after completion of resuscitation. Liver samples were collected, and total RNA
was isolated for reverse transcription–polymerase chain reaction
analysis of mRNA (TNF- , IL-1β, iNOS, and β-actin).
Results: MAP recovered more quickly in the AGD group than in the LR
group. Increased expression of liver mRNA for TNF- , IL-1β, and
iNOS was seen after hemorrhagic shock and resuscitation. AGD treatment
significantly reduced mRNA expression for all 3. Conclusions: AGD
modified the expression of genes controlling cytokines and iNOS in the liver.
This agent is a potential treatment for hemorrhagic shock.
Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 1,
32-36 (2007)
DOI: 10.1177/014860710703100132

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R. Yang, L. Martin-Hawver, C. Woodall, A. Thomas, N. Qureshi, D. Morrison, and C. Van Way III
Administration of Glutamine After Hemorrhagic Shock Restores Cellular Energy, Reduces Cell Apoptosis and Damage, and Increases Survival
JPEN J Parenter Enteral Nutr,
March 1, 2007;
31(2):
94 - 100.
[Abstract]
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