Pretreatment With Citrulline Improves Gut Barrier After Intestinal Obstruction in Mice

Abstract

Background: Citrulline has been shown to be an important marker of gut function, regulator of protein metabolism, and precursor of arginine. The authors assessed the effects of citrulline on gut barrier integrity and bacterial translocation (BT) in mice undergoing intestinal obstruction. Methods: Mice were divided into 3 groups: sham, intestinal obstruction (IO), and citrulline (CIT). The CIT group received a diet containing 0.6% citrulline; the IO and sham groups were fed a standard chow diet. On the eighth day of treatment, all animals received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with ^99mTechnetium (^99mTc-DTPA) by gavage for the intestinal permeability study. Terminal ileum was ligated except the sham group, which only underwent laparotomy. After 4, 8, and 18 hours, blood was collected to determine radioactivity. Samples of ileum were removed 18 hours after intestinal obstruction for histological analysis. In another set of animals, BT was evaluated. Animals received 10⁸ CFU/mL of ^99mTc–Escherichia coli by gavage; 90 minutes later, they underwent ileum ligation. Intestinal fluid and serum were collected to measure sIgA and cytokines. Results: The CIT group presented decreased intestinal permeability and BT when compared with the IO group (P < .05). Histopathology showed that citrulline preserved the ileum mucosa. The sIgA concentration was higher in the CIT group (P < .05). The IO group presented the highest levels of interferon-γ (P < .05). Conclusions: Pretreatment with citrulline was able to preserve barrier integrity and also modulated the immune response that might have affected BT decrease.