Effects of arginine replacement with L-citrulline on the arginine/nitric oxide metabolism in chickens: An animal model without urea cycle

Abstract

Background This study examined the efficacy of L-citrulline supplementation on the arginine/nitric oxide metabolism, and intestinal functions of broilers during arginine deficiency. A total of 288 day-old Arbor Acre broilers were randomly assigned to either an arginine deficient basal diet (NC diet), NC diet + 0.50% L-arginine (PC diet), or NC diet + 0.50% L-citrulline (NCL diet). Production performance was recorded, and at 21 days old, chickens were euthanized for tissue collection. Results The dietary treatments did not affect the growth performance of broilers (P > 0.05), although NC diet increased the plasma alanine aminotransferase, urate, and several amino acids, except arginine (P < 0.05). In contrast, NCL diet elevated the arginine and ornithine concentration higher than NC diet, and it increased the plasma citrulline greater than the PC diet (P < 0.05). The nitric oxide concentration in the kidney and liver tissues, along with the plasma and liver eNOS activities were promoted by NCL diet higher than PC diet (P < 0.05). In the liver, the activities of arginase 1, ASS, and ASL, as well as, the gene expression of iNOS and OTC were induced by PC diet greater than NC diet (P < 0.05). In the kidney, the arginase 1, ASS and ASL enzymes were also increased by PC diet significantly higher than the NC and NCL diets. Comparatively, the kidney had higher abundance of nNOS, ASS, ARG2, and OTC genes than the liver tissue (P < 0.05). In addition, NCL diet upregulated (P < 0.05) the mRNA expression of intestinal nutrient transporters (EAAT3 and PEPT1), tight junction proteins (Claudin 1 and Occludin), and intestinal mucosal defense (MUC2 and pIgR). The intestinal morphology revealed that both PC and NCL diets improved (P < 0.05) the ileal VH/CD ratio and the jejunal VH and VH/CD ratio compared to the NC fed broilers. Conclusion This study revealed that NCL diet supported arginine metabolism, nitric oxide synthesis, and promoted the intestinal function of broilers. Thus, L-citrulline may serve as a partial arginine replacement in broiler's diet without detrimental impacts on the performance, arginine metabolism and gut health of chickens.

The Role of the L-Arginine–Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease

“…Investigation into the transport and signaling mechanisms of arginine [ 56 ] and identifying the genetic and metabolic bases of arginine auxotrophy [ 59 ], the physio-pathological role of arginine derivates, and the interaction or competition between the enzymes involved in arginine metabolism [ 60 , 61 , 62 ] could represent important elements for understanding the pathogenesis and progression of ADPKD. The present study provides new data regarding the role of L-arginine–nitric oxide molecular pathway disturbances in ADPKD.…”

Beyond protein synthesis: the emerging role of arginine in poultry nutrition and host-microbe interactions

“…Citrulline bypasses the hepatic metabolism and can be converted to arginine in the kidneys and released into the bloodstream ( El-Hattab et al, 2012 ). Hence, citrulline can be used for the de novo synthesis of arginine in poultry ( Uyanga et al, 2023 ). Several studies in human subjects highlight the therapeutic applications of citrulline in different conditions such as skeletal muscle atrophy ( Ham et al, 2015 ), metabolic syndrome ( Sailer et al, 2013 ), and urea cycle disorders ( Johnson, 2017 ).…”

“…However, the potential role of citrulline in poultry health and disease is not understood completely. Citrulline can be used to partially replace arginine in broiler diets without causing a detrimental effect on the growth performance and intestinal health of the birds ( Uyanga et al, 2023 ). Citrulline supplementation in poultry increases the activity of the NOS enzyme, improves antioxidant synthesis, reduces lipid peroxidation, and modulates the availability of the free amino acids arginine, ornithine, and citrulline ( Uyanga et al, 2020 ).…”

“…Ornithine can be converted to pyrroline-5carboxylate further converted to proline and hydroxyproline. Proline and its metabolites regulate gene expression, mTOR pathway (van Meijl et al, 2010), protein synthesis, cell survival, and scavenge free radicals (Kaul et al, 2008). Besides, hydroxyproline is required for the synthesize of glycine, glucose, and pyruvate and is known to scavenge free radicals (Phang et al, 2008).…”