Impairment of arginine metabolism in rats after massive intestinal resection: effect of parenteral nutrition supplemented with citrulline compared with arginine

Abstract

Arginine homoeostasis is impaired in short bowel syndrome, but its supplementation in short bowel syndrome patients remains controversial. Recently, we demonstrated the benefits of citrulline supplementation by the enteral route in resected rats. Since the first step in managing short bowel syndrome is to initiate total parenteral nutrition, we hypothesized that parenteral citrulline supplementation would be more appropriate in this situation than arginine supplementation. In the present study, 24 rats were assigned to four groups. The sham group underwent transection whereas the three other groups underwent resection (R) of 80% of the small intestine. All rats were then fed exclusively by total parenteral nutrition as follows: supplementation with citrulline (R+CIT), with arginine (R+ARG) or no supplementation (R). All of the rats received isocaloric and isonitrogenous nutrition for 4 days. Nitrogen balance was measured daily. Rats were then killed and the blood was collected and the intestinal mucosa and extensor digitorum longus muscle were removed for amino acid and protein analysis. Citrulline and arginine increased mucosal protein content in the ileum (compared with sham and R, P<0.05). However, only citrulline prevented extensor digitorum longus atrophy (R+CIT, 130+/-3 mg compared with R, 100+/-6 mg and R+ARG, 110+/-2 mg, P<0.05). In addition, arginine worsened nitrogen balance (R+ARG, 104+/-46 mg/72 h compared with R, 249+/-69 mg/72 h, P<0.05). Only citrulline was able to prevent muscle atrophy and it was achieved independently from any noticeable effect on the gut in particular because citrulline and arginine share the same effect on mucosal ileal protein content. These results suggest that citrulline should be considered as a potential supplement for total parenteral nutrition of short bowel syndrome patients.

Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies

“…Interestingly, we observed a positive correlation between plasma CIT concentration (but not muscle CIT concentration) and S6K1 phosphorylation. Similar results were obtained in a previous study (34) in a model of short bowel syndrome rats in which the increase in muscle weight was correlated with CIT concentration in plasma but not in muscle. These correlations suggest that the CIT effect could be direct on the muscle signaling pathway.…”

The Role of L‐Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation

“…In the Arg–/– group, significantly increased intestinal permeability was observed 8 hours after the IO, but the permeability values later returned to baseline. It is well established that arginine may improve mucosal morphometric aspects and increase enterocyte proliferation and the number and height of villi under stress situations such as trauma, ischemia, intestinal resection, or obstruction 5 , 28 , 38 – 40 . Pretreatment with arginine ameliorated inflammation, epithelial reactivity and mucin depletion in iNOS–/– mice 41 .…”

Effect of intestinal resections on arginine metabolism: practical implications for nutrition support

“…The results of enteral citrulline supplementation provide a strong rationale for using citrulline, and not arginine, to supplement SBS patients [34,35 ]. There are situations in which it may be useful to provide a patient with arginine or citrulline, the most obvious being massive intestinal resection where the main site of citrulline production is greatly reduced.…”

“…As the first step in managing SBS is to initiate parenteral nutrition, it can be hypothesized that parenteral citrulline supplementation would be more appropriate in this situation than arginine supplementation [35 ]. In this last study 24 rats were assigned to four groups as in the previous study.…”

“…One study has supplemented citrulline instead of arginine by the enteral route [34] whereas a second study used the parenteral route [35 ]. In the enteral complementation study, 24 rats were assigned to four groups, citrulline (1 g/kg/day), arginine (0.994 g/kg/day), controls, and shams.…”