Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise

Abstract

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO 2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial

“…Despite the well-known anti-inflammatory properties of glutamine ( 20 , 21 , 38 ), we generally did not observe significant changes in the plasma levels of inflammatory biomarkers after 60 days of glutamine supplementation. The only exceptions were the reductions in plasma levels of ITAC and MIF in the placebo group from day 0 to day 60, but these changes were not clinically significant.…”

“…Despite the potential beneficial effects of glutamine, including activating the immune response, stimulating protein anabolism, protecting the intestinal barrier function, promoting an anti-inflammatory response ( 14 - 21 ), and providing protection against oxidative stress ( 21 ), there is a limited number of studies involving glutamine supplementation in older adults ( 18 , 19 , 22 ). Additionally, there is a lack of investigations into the tolerability of this amino acid among the older adult population.…”

Exercise sustains the hallmarks of health

“…Intestinal barrier permeability is impaired under heat stress 67 and with strenuous exercise 68 due, in part, to visceral hypoperfusion during exercise. Of note, glutamine supplementation appears to attenuate intestinal permeability and maintain intestinal integrity in response to a 60-min treadmill run at 70% of VO 2max in an environmental chamber set at 30 °C with 40%–45% humidity.…”

“… 72 Moreover, training improves zonula occludens 1, occludin, claudin-2, and the intestinal peptide transporter-1 messenger RNA expression. 68 Thus, physical exercise has an ambiguous, context-dependent effect on intestinal barrier integrity.…”

Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients’ Survival: A Randomized Controlled Trial

“…L-alanyl L-glutamine dipeptide (DIP) is a water-soluble compound that is used for nutritional purposes where it acts locally in the gastrointestinal (GI) tract to keep the integrity of the mucosa and preserve the intestinal functions [ 1 ]. Consequently, the use of DIP may help in reducing the incidence of bacterial infections and inflammation of the intestine and preventing related symptoms, such as diarrhea [ 2 ].…”