Protective effects of citrulline supplementation in ulcerative colitis rats

Abstract

It has been reported that supplementing certain amino acids has therapeutic effects on ulcerative colitis (UC). We intend to explore whether citrulline (Cit) supplementation has protective effects on UC. Fifteen male Wistar rats were divided into normal control group (NC group), UC group and UC+Cit group, with five rats in each group. The UC model was established by TNBS/ethanol method. Rats in UC+Cit group were intragastrically administered with Cit for 7 consecutive days after modeling. All rats were sacrificed after 7 days. Blood samples were collected to detect the number of monocytes. Colon tissues were taken for HE staining. Immunohistochemistry staining for CD68 and p-STAT3 were performed to detect the infiltration of monocytes and the phosphorylation of STAT3 in colon tissues. The concentrations of MCP-1, IL-6 and IL-17A and the protein expression of p-STAT3 in colon tissues were measured by ELISA and western blot methods, respectively. The body weight of UC group rats decreased significantly after 7 days (p<0.05). However, the weight loss of UC+Cit group rats was not statistically significant (p>0.05). The number of peripheral blood monocytes in UC+Cit group was significantly lower than that in UC group (p<0.05), and the infiltration of CD68-positive monocytes in the colon tissue of UC+Cit group was significantly reduced than that in UC group. The concentrations of MCP-1, IL-6 and IL-17A and the expression of p-STAT3 in colon tissues of UC+Cit group rats were significantly lower than those in UC group (both p<0.05). Our study suggests that Cit supplementation may be a potential therapy for UC.

Potential Implications of Citrulline and Quercetin on Gut Functioning of Monogastric Animals and Humans: A Comprehensive Review

“…Citrulline has been demonstrated as efficacious in IBD models typically induced as Crohn's disease or ulcerative colitis [88]. Using an ulcerative colitis model in rats, citrulline supplementation elicited protective effects in restoring body weight, and lowered the histopathology score and pro-inflammatory factors (MCP-1, IL-6, IL-17A, and p-STAT3) in colon tissues, possibly by improving the structural integrity and absorptive function of the intestine [135]. Citrulline is a reliable marker of intestinal malabsorption [136], and besides its role as a marker of enterocyte function, citrulline has been found to reflect gut dysbiosis induced by antibiotics [137].…”

Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature

“…Amino acids (AA) are important nutrients that are involved in key physiological functions, including protein synthesis, cell turnover, tissue repair, gluconeogenesis, wound healing, and immune response ( Cai et al, 2020 ). They act as essential precursors for various molecules and they exhibit metabolic and regulatory roles that are vital to the growth, development, health, and homeostasis of living organisms.…”

Metabolic effects of L‐citrulline in type 2 diabetes

“…112 In rodents, doses of 0.05, 163 0.2, 61 0.3, 170 0.4, 61 0.5, 155 0.6, 164,170 0.8, 61 0.9, 170-172 1, 155 5, 158 and 5.7 173 g/kg have been used for durations of 7, 158,170-172 14, 163 21, 61 28, 156,162 56, 169 63, 155,173 77, 155 and 105 164 days in male mice, 155,163,164,173 male rats. 61,155,156,158,[170][171][172] Literature indicates that doses as high as 15 g/day 92 and 5.7 g/kg 173 are well tolerated in humans and animals, respectively. In a clinical trial, Cit (15 g/day for 2 weeks) was used for restoring NO bioavailability of airways in obese subjects with asthma; some side effects, including mild to severe nausea (12%-41%), headache (17%-44%), lightheadedness (3%-20%), and diarrhea (13%) have been reported.…”

“…Thus, it has been suggested that the minimum and maximum effective doses of Cit for treating cardiometabolic disorders in humans are approximately 3 and 10 g/day, respectively 112 . In rodents, doses of 0.05, 163 0.2, 61 0.3, 170 0.4, 61 0.5, 155 0.6, 164,170 0.8, 61 0.9, 170–172 1, 155 5, 158 and 5.7 173 g/kg have been used for durations of 7, 158,170–172 14, 163 21, 61 28, 156,162 56, 169 63, 155,173 77, 155 and 105 164 days in male mice, 155,163,164,173 male rats 61,155,156,158,170–172 …”