Oral post-treatment supplementation with a combination of glutamine, citrulline, and antioxidant vitamins additively mitigates jejunal damage, oxidative stress, and inflammation in rats with intestinal ischemia and reperfusion

PLoS One. 2024 Feb 2;19(2):e0298334. doi: 10.1371/journal.pone.0298334. eCollection 2024.

Abstract

Introduction: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation.

Method: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls.

Results: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index.

Conclusion: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Citrulline / metabolism
  • Citrulline / pharmacology
  • Cytokines / metabolism
  • DNA / metabolism
  • Dietary Supplements
  • Glutamine / metabolism
  • Glutamine / pharmacology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Ischemia / complications
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Reperfusion Injury* / metabolism
  • Vitamins / pharmacology

Substances

  • Antioxidants
  • Vitamins
  • Glutamine
  • Citrulline
  • Cytokines
  • DNA

Grants and funding

This work is supported by the National Science Council of the Republic of China (NSC 98-2320-B-030-003-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.