Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related genes in hemorrhagic shock.

Abstract

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-alpha), interleukin-1 (IL-1beta) 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-alpha, IL-1beta, iNOS, and beta-actin).

RESULTS:

MAP recovered more quickly in the AGD group than in the LR group. Increased expression of liver mRNA for TNF-alpha, IL-1beta, 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.

• Authors: Rongjie Yang, Xiaoyu Tan, Ann M Thomas, Robert Steppacher, Nilofer Qureshi, David C Morrison, Charles W Van Way 3rd
• Journal: JPEN. Journal of parenteral and enteral nutrition (JPEN J Parenter Enteral Nutr) 2007 Jan-Feb Vol. 31 Issue 1 Pg. 32-6 ISSN: 0148-6071 [Print] United States
• PMID: 17202438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Interleukin-1beta
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Glutamine
• Nitric Oxide Synthase Type II
• Alanine

Topics

• Alanine (therapeutic use)
• Animals
• Gene Expression Regulation
• Glutamine (therapeutic use)
• Interleukin-1beta (biosynthesis)
• Liver (enzymology, metabolism)
• Male
• Nitric Oxide Synthase Type II (metabolism)
• RNA, Messenger (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Shock, Hemorrhagic (drug therapy)
• Tumor Necrosis Factor-alpha (metabolism)