Preventive effect of glutamine on intestinal barrier dysfunction induced by severe trauma

Abstract

AIM: To investigate the mechanism underlying intestinal barrier function damage after severe trauma and the therapeutic effect of glutamine. METHODS:Burned patients, and animal models of severe trauma replicated by hemorrhagic shock combined with endotoxin infusion and burn injury, were included in a serial experiment. Effects of oral glutamine on intestinal barrier function were observed in scalded rats. Parameters measured in these experiments were as follows: plasma levels of diamine oxidase (DAO), tumor necrosis factor (TNFα α α α α), endotoxin (LPS), and lactate as well as D-lactate by biochemical methods, lactose/mannitol (L/M) ratio in urine by SP-3400, and pathological examination of intestinal mucosa under light microscopy. RESULTS: INTRODCTIONIt is generally accepted that the intestine may serve as an important organ in the development of severe complications under critically ill conditions, including trauma, burns, shock, etc.[1-3] Hemorrhagic shock and/or gut ischemia-reperfusion injury commonly occur in the early stage after acute insults, leading to gut-derived sepsis as a result of gut barrier dysfunction [4][5][6][7][8][9][10] . In order to investigate the mechanism underlying intestinal barrier function damage and its potential interventional measures, burned patients and animal models of severe trauma were employed in our current experiments [6,[11][12][13][14][15] . MATERIALS AND METHODS Animal modelsAnimal models of severe trauma were replicated by hemorrhagic shock combined with endotoxin infusion. Male Wistar rats, weighing 190g-230g, were anaesthetized with intraperitoneal injection of 30g·L -1 barbitone sodium (35mg·kg -1 ), and the femoral artery and jugular vein were cannulated under aseptic conditions. The rats were then bled via the jugular vein catheter until a mean arterial pressure of 30-35 mmHg (4.6 kPa) was reached. At the end of shock, endotoxin (E.coliO55 B5, Sigma) was infused through tail vein at a dose of 2mg·kg -1 . A goat model of hemorrhagic shock combined with endotoxin challenge was established according to the previous report(n=20) [5] . Animals received E.coliO26 B6 endotoxin via portal vein 24h after the recovery from shock, and the dosage was 30 ng·kg -1 ·min -1, which was given in a continuous infusion lashing for 5d. Wistar rats were divided randomly into three groups: normal controls, early feeding with standard feed plase Gln 0.5g after scalding, and animals (except control group) sustained a 30% TBSA fullthickness scald covering the back and flanks [6] . Determination of plasma diamine oxidase in 21 burned patients (17 male and 4 female) at the age of 33±10 years, with burn area (64±21)%, and (35±20)% 0. Plasma DAO activity was determined on day 1, 3, 7, 14 and 21 postburn.Blood and intestinal DAO levels were tested according to our previous report [17] . Plasma lactate and Dlactate concentrations were determined by biochemical methods as described by Brandt et al [18] . Microassay for quantitation of endotoxin in blood was made with new PCA treatment...

Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

“…Lactadherin is crucially involved in reducing the incidence of RV-associated diarrhea and relevant diarrheal symptoms (4,14,15). Previous studies have demonstrated that breast milk contains lactadherin with a specific sequence, i.e., N'-Arg-Gly-Asp (RGD) crosslinked with integrin α V β 3 and α V β 5 , thus competitively inhibiting the RV combination with host cells (12,(14)(15)(16)(17). The results of the present study demonstrated that, following infection with RV, rats in the groups treated with lactadherin, LBRI and LARI, exhibited less severe diarrheal symptoms, as compared with the RVI group.…”

“…Specimens were subsequently rinsed three times with PBS for 5 min and developed using 3,3'-diaminobenzidine reagent (Wuhan Boster Biological Technology, Ltd., Wuhan, China). Hematoxylin counterstaining was performed and the specimens were mounted using the conventional method (12). Five fields of view were randomly selected and images of the intestinal mucosal layer were captured using a light microscope (magnification, x40).…”

Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock

“…In addition to the liver, intestine also contributes to the systemic inflammatory response and acute phase proteins expression [10] and this intestinal acute phase response may be influenced by protein malnutrition [11,12] . Although glutamine has traditionally been recognized as a nonessential amino acid, recent studies have demon-strated that glutamine plays a major role in the response to injury [13] , in the enterocyte oxidative metabolism [14] , and in the maintenance of the intestinal epithelium [15,16] . Glutamine supplementation may prevent gut mucosal damage and bacterial translocation in various experimental models of gut injury [13,17] .…”

“…Although glutamine has traditionally been recognized as a nonessential amino acid, recent studies have demon-strated that glutamine plays a major role in the response to injury [13] , in the enterocyte oxidative metabolism [14] , and in the maintenance of the intestinal epithelium [15,16] . Glutamine supplementation may prevent gut mucosal damage and bacterial translocation in various experimental models of gut injury [13,17] . Moreover, glutamine could with stand systemic [18] but also gut-associated [19,20] immune response, because glutamine is an important substrate for optimal lymphocyte [21] and macrophage [22] function.…”

Prevention and treatment of gastrointestinal dysfunction following severe burns: A summary of recent 30-year clinical experience

“…TNF-α content was measured by radioimmunoassay. The activity of diamine oxidase (DAO) in plasma was tested according to the previous report [7] .…”