Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related genes in hemorrhagic shock.
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.
Yang
Rongjie
R
Department of Surgery, University of Missouri-Kansas City, 4108, USA.
Tan
Xiaoyu
X
Thomas
Ann M
AM
Steppacher
Robert
R
Qureshi
Nilofer
N
Morrison
David C
DC
Van Way
Charles W
CW
D000409:Alanine / Q000627:therapeutic use*; D000818:Animals; D005786:Gene Expression Regulation; D005973:Glutamine / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D052247:Nitric Oxide Synthase Type II; D000409:Alanine