{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:37:48Z","timestamp":1781926668893,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"earmarked fund for China Agriculture Research System","award":["CARS-43-G-2"],"award-info":[{"award-number":["CARS-43-G-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>This study aimed to investigate the effects of arginine (Arg) or N-carbamylglutamate (NCG) on jejunum development, the global arginine bioavailability ratio (GABR), and stress-related indices in young rex rabbits. Forty-five litters of newborn rabbits with similar litter weights and sizes were randomly divided into five groups and fed a basal diet (con group), basal diet + 0.3% Arg (0.3% Arg group), basal diet + 0.6% Arg (0.6% Arg group), basal diet + 0.03% NCG (0.03% NCG group), or basal diet + 0.06% NCG (0.06% NCG group). After weaning at 35 days, eight healthy young rabbits with similar body weights were selected from each group and slaughtered on the 36th day. Serum and jejunum samples were collected for index analysis. Arg or NCG significantly affected the jejunum structure development in the young rabbits. The villus height (V) in the treatment groups was significantly higher than that in the con group (p &lt; 0.05) and was highly significantly improved in the 0.6% Arg group (p &lt; 0.01). The crypt depth (C) in 0.6% Arg and 0.06% NCG groups was significantly lower than that in the con, 0.3% Arg, and 0.03% NCG groups (p &lt; 0.05). Compared with the con group, the V\/C ratio was significantly increased in the treatment groups (p &lt; 0.05) and was excessively and significantly increased in the 0.6% Arg and 0.06% NCG groups (p &lt; 0.01). Compared with the con group, the Nitric-Oxide (NO) levels and inducible Nitric-Oxide Synthase (iNOS) activity in serum were significantly increased in the treatment groups. The NO levels in the jejunum were also increased in the treatment groups; however, there were no significant differences (p &gt; 0.05). The iNOS activity and mRNA expression in the jejunum of the 0.6% Arg and 0.06% NCG groups were significantly higher than those in the con group (p &lt; 0.05). Compared with the con group, the concentration of serum corticosterone in the 0.3% Arg, 0.6% Arg, and 0.06% NCG groups was significantly reduced. Adding Arg or NCG to the basal diet significantly increased the concentration and gene mRNA expression levels of heat shock protein 70 (HSP70) in the jejunum (p &lt; 0.05). The expression level in the 0.6% Arg and 0.06% NCG groups was significantly higher than that in the con group (p &lt; 0.01). At 36 days, Arg and NCG improved the GABR. In the 0.6% Arg group, the GABR was increased by 16.92%. The GABR was &lt;0.8 at the time of weaning. The Arg levels in the body did not meet the needs of the young animals. In the trial, Arg or NCG supplementation in the diet significantly increased iNOS activity and gene mRNA expression, promoting NO synthesis. Thus, it can improve jejunal morphological and structural development. Adding Arg or NCG increased HSP70 mRNA expression levels, enhanced intestinal stress tolerance, and improved intestinal health. During the lactation period, adding Arg or NCG increased the GABR, but the GABR was &lt;0.8 during weaning.<\/jats:p>","DOI":"10.3390\/ani15101354","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:47:15Z","timestamp":1746686835000},"page":"1354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Supplementation of Arginine or N-Carbamylglutamate Affects Jejunum Development, Global Arginine Bioavailability Ratio, and Stress-Related Indices in Young Rex Rabbits"],"prefix":"10.3390","volume":"15","author":[{"given":"Feng","family":"Qin","sequence":"first","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Longyan University, Longyan 364012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Shao","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"Key Laboratory of Crop and Livestock Integrated Farming, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.livsci.2006.09.005","article-title":"Review on the Interactions between Gut Microflora and Digestive Mucosal Immunity. Possible Ways to Improve the Health of Rabbits","volume":"107","author":"Boullier","year":"2007","journal-title":"Livest. Sci."},{"key":"ref_2","first-page":"15","article-title":"New Trends in Rabbit Feeding: Influence of Nutrition on intestinal health","volume":"6","author":"Badiola","year":"2008","journal-title":"Span. J. Agric. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zemzmi, J., R\u00f3denas, L., Blas, E., Najar, T., and Pascua, J.J. (2020). Characterisation and in Vitro Evaluation of Fenugreek (Trigonella foenum-graecum) Seed Gum as a Potential Prebiotic in Growing Rabbit Nutrition. Animals, 10.","DOI":"10.3390\/ani10061041"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00726-010-0538-y","article-title":"Dietary supplementation with L-arginine or N-carbamylglutamate enhances intestinal growth and heat shock protein-70 expression in weanling pigs fed a corn- and soybean meal-based diet","volume":"39","author":"Wu","year":"2010","journal-title":"Amino Acids"},{"key":"ref_5","first-page":"2783","article-title":"Effects of arginine on intestinal growth, tissue morphology and IL-2 gene expression in early weaned piglets","volume":"41","author":"Tan","year":"2008","journal-title":"Chin. Agric. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1023\/A:1024167428092","article-title":"Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome","volume":"48","author":"Sukhotnik","year":"2003","journal-title":"Dig. Dis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"G157","DOI":"10.1152\/ajpgi.00005.2001","article-title":"Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum","volume":"283","author":"Gookin","year":"2002","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1681S","DOI":"10.1093\/jn\/137.6.1681S","article-title":"Arginine and immunity","volume":"137","author":"Popovic","year":"2007","journal-title":"J. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1097\/01.WCB.0000059586.71206.F3","article-title":"Role of nitric oxide in cerebral blood flow abnormalities after traumatic brain injury","volume":"23","author":"Hlatky","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1016\/j.jacc.2009.02.036","article-title":"Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk","volume":"53","author":"Tang","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cardfail.2013.01.001","article-title":"Diminished global arginine bioavailability as a metabolic defect in chronic systolic heart failure","volume":"19","author":"Tang","year":"2013","journal-title":"J. Card. Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.atherosclerosis.2011.04.041","article-title":"Arginine bioavailability ratios are associated with cardiovascular mortality in patients referred to coronary angiography","volume":"218","author":"Sourij","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_13","first-page":"40","article-title":"Effects of N-carbamylglutamate or arginine on production performance of lactation doe and growth performance, antioxidant ability of weaning rabbit","volume":"49","author":"Zhang","year":"2017","journal-title":"Anim. Husb. Vet. Med."},{"key":"ref_14","unstructured":"NRC (1977). Nutrition Requirements of Rabbits. Report of the Committee on Animal Nutrition, National Academy Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jss.2004.07.004","article-title":"Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia in rat","volume":"122","author":"Sukhotnik","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_16","first-page":"504","article-title":"Protective role of arginine in gut barrier dysfunction induced by total parenteral nutrition","volume":"25","author":"Bao","year":"2007","journal-title":"J. Clin. Pediatr."},{"key":"ref_17","unstructured":"Sun, X.M. (2019). Effect of L-Arginine and N-Carbamylgluatmate on Small Intestinal Villi Development and Cecal Microbiota Composition of Young Rabbits. [Ph.D. Thesis, Jilin University]. (In Chinese)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s00726-013-1643-5","article-title":"Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs","volume":"46","author":"Yin","year":"2014","journal-title":"Amino Acids"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1017\/S000711451000365X","article-title":"Dietary L-arginine supplementation enhances intestinal development and expression of vascular endothelial growth factor in weanling piglets","volume":"105","author":"Yao","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00726-015-1921-5","article-title":"Safety of long-term dietary supplementation with L-arginine in pigs","volume":"47","author":"Hu","year":"2015","journal-title":"Amino Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jff.2018.11.019","article-title":"Arginine supplementation reduces colonic injury, inflammation and oxidative stress of DSS-induced colitis in mice","volume":"52","author":"Andrade","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.fsi.2014.11.030","article-title":"In vitro and in vivo protective effect of arginine against lipopolysaccharide induced inflammatory response in the intestine of juvenile Jian carp (Cyprinus carpio var. Jian)","volume":"42","author":"Jiang","year":"2015","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_23","first-page":"2035","article-title":"Effect of Arginine on Intestinal Health of Weaner Piglets and related Mechanisms","volume":"26","author":"Ren","year":"2014","journal-title":"Chin. J. Anim. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.aninu.2016.04.005","article-title":"Arginine, N-carbamylglutamate, and glutamine exert protective effects against oxidative stress in rat intestine","volume":"2","author":"Xiao","year":"2016","journal-title":"Anim. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00431-009-1036-7","article-title":"Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia","volume":"169","author":"Schwahn","year":"2010","journal-title":"Eur. J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11011-009-9155-4","article-title":"The first use of N-carbamylglutamate in a patient with decompensated maple syrup urine disease","volume":"24","author":"Ucar","year":"2009","journal-title":"Metab. Brain Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zeng, X.F., Huang, Z.M., Mao, X.B., Wang, J.J., Wu, G.Y., and Qiao, S.Y. (2012). N-carbamylglutamate enhances pregnancy outcome in rats through activation of the PI3K\/PKB\/mTOR signaling pathway. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041192"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00726-006-0477-9","article-title":"Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences","volume":"33","author":"Blachier","year":"2007","journal-title":"Amino acids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00726-008-0148-0","article-title":"Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs","volume":"37","author":"Tan","year":"2009","journal-title":"Amino acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00726-008-0210-y","article-title":"Arginine metabolism and nutrition in growth, health and disease","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1111\/j.1476-5381.1994.tb14887.x","article-title":"Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors","volume":"111","author":"Laszlo","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0014-5793(95)00801-F","article-title":"Nitric oxide is involved in heat-induced HSP70 accumulation","volume":"370","author":"Iyu","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_33","first-page":"323","article-title":"Markers of acute stress in pigs","volume":"56","author":"Svoboda","year":"2007","journal-title":"Physiol. Res."},{"key":"ref_34","first-page":"81","article-title":"Effect of transport stress on behavior, serum corticosterone and nNOS expression in the SON of rats","volume":"21","author":"Yu","year":"2016","journal-title":"J. China Agric. Univ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0006-8993(93)91739-F","article-title":"Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro","volume":"605","author":"Costa","year":"1993","journal-title":"Brain Res."},{"key":"ref_36","unstructured":"Liu, Q.T. (2015). Study on the Effect of Growth Performance, Serum Physio-Biochemical Indices and Immune Performance on Growing-Finishing Pigs by Adding Cysteamine and N-Carbamylglutamic. [Ph.D. Thesis, Guangxi University]. (In Chinese)."},{"key":"ref_37","unstructured":"Zheng, P. (2010). The Study on Effects of Oxidative Stress and Mechanism on the Characteristics of Arginine Metabolism and Requirement in Piglets. [Ph.D. Thesis, Sichuan Agricultural University]. (In Chinese)."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1093\/jn\/132.9.2551","article-title":"Weaning affects the expression of heat shock proteins in different regions of the gastrointestinal tract of piglets","volume":"132","author":"David","year":"2002","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2006.07.028","article-title":"Role of heat shock proteins (molecular chaperones) in intestinal mucosal protection","volume":"348","author":"Otaka","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/pmic.200600715","article-title":"Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response","volume":"7","author":"Lenaerts","year":"2007","journal-title":"Proteomics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00726-009-0264-5","article-title":"Amino acids and gaseous signaling","volume":"37","author":"Li","year":"2009","journal-title":"Amino Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00726-008-0213-8","article-title":"Dietary arginine supplementation enhances antioxidative capacity and improves meat quality of finishing pigs","volume":"38","author":"Ma","year":"2010","journal-title":"Amino Acids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00726-009-0246-7","article-title":"High fat feeding and dietary L-arginine supplementation differentially regulate gene expression in rat white adipose tissue","volume":"37","author":"Jobgen","year":"2009","journal-title":"Amino Acids"},{"key":"ref_44","first-page":"141","article-title":"Global arginine bioavailability ratio is decreased in patients with major depressive disorder","volume":"229","author":"Tolmunen","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bbi.2015.10.015","article-title":"Global arginine bioavailability, a marker of nitric oxide synthetic capacity, is decreased in PTSD and correlated with symptom severity and markers of inflammation","volume":"52","author":"Bersani","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_46","first-page":"5965721","article-title":"Metabolites of the nitric oxide (NO) pathway are altered and indicative of reduced NO and arginine bioavailability in patients with cardiometabolic diseases complicated with chronic wounds of lower Extremities: Targeted Metabolomics Approach (LC-MS\/MS)","volume":"2019","author":"Fleszar","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31","DOI":"10.30548\/vascfail.3.2_31","article-title":"Decreased arginine bioavailability in patients with coronary artery disease in an outpatient setting","volume":"3","author":"Miyazaki","year":"2020","journal-title":"Vasc. Fail."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/10\/1354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:29:18Z","timestamp":1760030958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/10\/1354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ani15101354"],"URL":"https:\/\/doi.org\/10.3390\/ani15101354","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,8]]}}}