{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:49:22Z","timestamp":1791287362468,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Agriculture Research System of Ministry of Finance and Ministry of Agriculture and Rural Affairs","award":["CARS36"],"award-info":[{"award-number":["CARS36"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Weaning stress affects the health and performance of calves. L-glutamine (L-Gln) is commonly used as a functional antioxidant and energy supplement in the body. However, dietary L-Gln supplementation improving weaning stress of calves is unclear. Thus, we aimed to explore the effects of L-Gln (provided by rumen-protected L-Gln) on calves during weaning. Seventy-five Holstein calves (54.0 \u00b1 2.68 kg; 42 \u00b1 2.1 d of age) were assigned to five groups: no supplementation and L-Gln with 1%, 2%, 3%, and 4% dry matter daily intake (DMI) supplementation groups, respectively. The experiment lasted for 28 days (42\u201370 d of age of calves), and the calves were weaned at 15 d of experiment. DMI and body weekly weight of all calves were recorded. Blood samples of nine healthy calves with similar body weight were collected from each group at 0, 7, 14, 16, 18, 21, and 28 d of experiment for detecting serum L-Gln, glucose, insulin, urea nitrogen, D-lactate, cortisol, haptoglobin, interleukin-8, immunoglobulin (Ig) G, IgA, IgM, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde. At the end of the experiment, six healthy calves with similar body weight from each group were selected for slaughter and morphological analysis of small intestine tissue. The results showed that the L-Gln supplementation in the diets improved the negative effects of sudden weaning in calves. Furthermore, compared to the higher-level L-Gln supple-mentation (3 and 4% of DMI) groups, the dietary lower-level L-Gln supplementation (1 and 2% of DMI) had higher average daily gain, glutathione peroxidase and IgG concentration, and villus height\/crypt depth of the duodenum and jejunum, as well as lower cortisol, haptoglobin, and interleukin-8 concentration of weaned calves. These results provided effective reference for relieving the negative effects of calves during weaning.<\/jats:p>","DOI":"10.3390\/antiox11030542","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effect of Supplementing Different Levels of L-Glutamine on Holstein Calves during Weaning"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-0612","authenticated-orcid":false,"given":"Shuo","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Sunlon Livestock Development Co., Ltd., Beijing 100076, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanlin","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-9462","authenticated-orcid":false,"given":"Zhijun","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanliang","family":"Bi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2527\/1999.772323x","article-title":"Comparison of three weaning ages on cow-calf performance and steer carcass traits","volume":"77","author":"Myers","year":"1999","journal-title":"J. Anim. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Diao, Q., Zhang, R., and Fu, T. (2019). Review of Strategies to Promote Rumen Development in Calves. Animals, 9.","DOI":"10.3390\/ani9080490"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"933","DOI":"10.2527\/2005.834933x","article-title":"The effect of early weaning on feedlot performance and measures of stress in beef calves","volume":"83","author":"Arthington","year":"2005","journal-title":"J. Anim. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1751-0147-53-28","article-title":"Minimising the stress of weaning of beef calves: A review","volume":"53","author":"Ungerfeld","year":"2011","journal-title":"Acta Vet. Scand."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0301-6226(97)00057-2","article-title":"Factors influencing the structure and function of the small intestine in the weaned pig: A review","volume":"51","author":"Pluske","year":"1997","journal-title":"Livest. Prod. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, S., Ma, T., Zhao, G., Zhang, N., Tu, Y., Li, F., Cui, K., Bi, Y., Ding, H., and Diao, Q. (2019). Effect of Age and Weaning on Growth Performance, Rumen Fermentation, and Serum Parameters in Lambs Fed Starter with Limited Ewe-Lamb Interaction. Animals, 9.","DOI":"10.3390\/ani9100825"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/jn\/138.6.1025","article-title":"Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation","volume":"138","author":"Wang","year":"2008","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0022-4804(90)90080-L","article-title":"The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection","volume":"48","author":"Souba","year":"1990","journal-title":"J. Surg. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1177\/0148607198022004224","article-title":"Glutamine enhances gut glutathione production","volume":"22","author":"Cao","year":"1998","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"skab305","DOI":"10.1093\/jas\/skab305","article-title":"Combined supplementation of sodium humate and glutamine reduced diarrhea incidence of weaned calves by intestinal microbiota and metabolites changes","volume":"99","author":"Wang","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1056\/NEJMoa1212722","article-title":"A randomized trial of glutamine and antioxidants in critically ill patients","volume":"368","author":"Heyland","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1590\/S1519-99402014000400013","article-title":"Inclusion of glutamine associated with glutamic acid in the diet of piglets weaned at 21 days of age","volume":"15","author":"Teixeira","year":"2014","journal-title":"Rev. Bras. Saude E Prod. Anim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3945\/jn.115.224857","article-title":"L-Glutamine Enhances Tight Junction Integrity by Activating CaMK Kinase 2-AMP-Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells","volume":"146","author":"Wang","year":"2016","journal-title":"J. Nutr."},{"key":"ref_14","first-page":"365","article-title":"Effects of monosodium l glutamate on diet palatability and piglet performance during the suckling and weaning periods","volume":"50","author":"Gatel","year":"1990","journal-title":"Anim. Prod."},{"key":"ref_15","first-page":"E408","article-title":"Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets","volume":"273","author":"Reeds","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.dci.2006.03.003","article-title":"Glutamine supplementation influences immune development in the newly weaned piglet","volume":"30","author":"Johnson","year":"2006","journal-title":"Dev. Comp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1017\/S1751731119001800","article-title":"Review: The roles and functions of glutamine on intestinal health and performance of weaning pigs","volume":"13","author":"Ji","year":"2019","journal-title":"Animal"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.3168\/jds.2019-17529","article-title":"Effect of arginine or glutamine supplementation and milk feeding allowance on small intestine development in calves","volume":"103","author":"Khan","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1080\/09712119.2018.1436549","article-title":"Evaluation of milk replacer supplemented with lysine and methionine in combination with glutamate and glutamine in dairy calves","volume":"46","author":"Manzoni","year":"2018","journal-title":"J. Appl. Anim. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.3168\/jds.2021-21009","article-title":"Early step-down weaning of dairy calves from a high milk volume with glutamine supplementation","volume":"105","author":"Wickramasinghe","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/jpn.12002","article-title":"Effect of parenteral administration of glutamine on autophagy of liver cell and immune responses in weaned calves","volume":"97","author":"Hu","year":"2013","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"118457","DOI":"10.1016\/j.envpol.2021.118457","article-title":"Enzymatic probe sonication for quick extraction of total bisphenols from animal-derived foods: Applicability to occurrence and exposure assessment","volume":"292","author":"Xiao","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_23","unstructured":"NRC (2001). Nutrient Requirement of Dairy Cattle, National Academic Press."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1093\/ps\/86.9.1940","article-title":"The effect of supplemental glutamine on growth performance, development of the gastrointestinal tract, and humoral immune response of broilers","volume":"86","author":"Bartell","year":"2007","journal-title":"Poult. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100108","DOI":"10.1016\/j.animal.2020.100108","article-title":"Dietary supplementation with glutamine improves gastrointestinal barrier function and promotes compensatory growth of growth-retarded yaks","volume":"15","author":"Ma","year":"2021","journal-title":"Animal"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2460\/ajvr.1991.53.04.551","article-title":"Effect of initial restraint, weaning, and transport stress on baseline and ACTH-stimulated cortisol responses in beef calves of different genotypes","volume":"53","author":"Zavy","year":"1992","journal-title":"Am. J. Vet. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00580-012-1654-8","article-title":"Acute-phase proteins and oxidative stress biomarkers in water buffalo calves subjected to transportation stress","volume":"23","year":"2014","journal-title":"Comp. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.rvsc.2014.06.003","article-title":"Biomarker responses to weaning stress in beef calves","volume":"97","author":"McGee","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.5713\/ajas.2003.1770","article-title":"Effect of Dietary Glutamine Supplement on Performance and Intestinal Morphology of Weaned Pigs","volume":"16","author":"Lee","year":"2003","journal-title":"Asian Australas. J. Anim. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1093\/jn\/127.11.2253","article-title":"Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs","volume":"127","author":"Yoo","year":"1997","journal-title":"J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: Metabolism, functions, and nutrition","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1089\/ars.2010.3830","article-title":"The cystine\/cysteine cycle and GSH are independent and crucial antioxidant systems in malignant melanoma cells and represent druggable targets","volume":"15","author":"Castellani","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.freeradbiomed.2011.10.489","article-title":"Regulation of prostate cancer cell invasion by modulation of extra- and intracellular redox balance","volume":"52","author":"Chaiswing","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/abbi.2001.2739","article-title":"Molecular evolution and structure\u2014Function relationships of the superoxide dismutase gene families in angiosperms and their relationship to other eukaryotic and prokaryotic superoxide dismutases","volume":"399","author":"Fink","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sakai, O., Uchida, T., Roggia, M.F., Imai, H., Ueta, T., and Amano, S. (2015). Role of Glutathione Peroxidase 4 in Glutamate-Induced Oxytosis in the Retina. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130467"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ccell.2014.12.006","article-title":"Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth","volume":"27","author":"Jin","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/S0022-2828(95)90656-8","article-title":"Detection of oxidative stress in heart by estimating the dinitrophenylhydrazine derivative of malonaldehyde","volume":"27","author":"Cordis","year":"1995","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wu, M., Xiao, H., Ren, W., Yin, J., Tan, B., Liu, G., Li, L., Nyachoti, C.M., Xiong, X., and Wu, G. (2014). Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100591"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.fsi.2016.07.002","article-title":"Changes in integrity of the gill during histidine deficiency or excess due to depression of cellular anti-oxidative ability, induction of apoptosis, inflammation and impair of cell-cell tight junctions related to Nrf2, TOR and NF-\u03baB signaling in fish","volume":"56","author":"Jiang","year":"2016","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1084\/jem.193.11.1311","article-title":"CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade","volume":"193","author":"Taylor","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_41","first-page":"225","article-title":"Effect of protected-glutamine supplementation on performance, milk composition and some blood metabolites in fresh Holstein cows","volume":"19","author":"Nemati","year":"2018","journal-title":"Iran. J. Vet. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.3168\/jds.S0022-0302(06)72585-1","article-title":"Effect of postruminal glutamine supplementation on immune response and milk production in dairy cows","volume":"89","author":"Doepel","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/MOG.0b013e3283438dea","article-title":"Innate immunity in the small intestine","volume":"27","author":"Santaolalla","year":"2011","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.3168\/jds.S0022-0302(06)72236-6","article-title":"Supplementation of 1% L-glutamine to milk replacer does not overcome the growth depression in calves caused by soy protein concentrate","volume":"89","author":"Drackley","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7336","DOI":"10.3168\/jds.2012-5881","article-title":"Short communication: Glutamine increases autophagy of liver cells in weaned calves","volume":"95","author":"Hu","year":"2012","journal-title":"J. Dairy Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-animal-013020-020412","article-title":"Concepts and Consequences of a Core Gut Microbiota for Animal Growth and Development","volume":"10","author":"Perlman","year":"2021","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev-animal-021419-083952","article-title":"The Role of the Gut Microbiome in Cattle Production and Health: Driver or Passenger?","volume":"8","author":"Neves","year":"2020","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100316","DOI":"10.1016\/j.animal.2021.100316","article-title":"Review: The development of the gastrointestinal tract microbiota and intervention in neonatal ruminants","volume":"15","author":"Zhang","year":"2021","journal-title":"Animal"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6623","DOI":"10.1007\/s00253-020-10684-y","article-title":"Effects of dietary rumen-protected Lys levels on rumen fermentation and bacterial community composition in Holstein heifers","volume":"104","author":"Kong","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1038\/s41467-020-15652-8","article-title":"Stochasticity constrained by deterministic effects of diet and age drive rumen microbiome assembly dynamics","volume":"11","author":"Furman","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Abdelsattar, M.M., Zhuang, Y., Cui, K., Bi, Y., Haridy, M., and Zhang, N. (2022). Longitudinal investigations of anatomical and morphological development of the gastrointestinal tract in goats from colostrum to postweaning. J. Dairy Sci.","DOI":"10.3168\/jds.2021-21056"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10136","DOI":"10.3168\/jds.2020-18630","article-title":"Effects of rumen-protected methionine or methionine analogs in starter on plasma metabolites, growth, and efficiency of Holstein calves from 14 to 91 d of age","volume":"103","author":"Molano","year":"2020","journal-title":"J. Dairy Sci."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:35:36Z","timestamp":1760135736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,12]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["antiox11030542"],"URL":"https:\/\/doi.org\/10.3390\/antiox11030542","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,12]]}}}