{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:30:41Z","timestamp":1788543041766,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of Henan Province","award":["202102110131"],"award-info":[{"award-number":["202102110131"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515011200"],"award-info":[{"award-number":["2021A1515011200"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Foundation of Guangdong University of Petrochemical Technology","award":["2020rc026"],"award-info":[{"award-number":["2020rc026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The Maillard reaction between the lactose and milk proteins unavoidably occurs during the thermal treatment of milk. Although the impact of this reaction on protein nutrition and safety has been well-studied, whether a lactose glycation of milk proteins of the Maillard-type might affect the rats in their growth and intestinal morphology needs an investigation. In this study, caseinate and lactose-glycated caseinate were digested using pepsin and trypsin. Afterward, the resultant caseinate digest and glycated caseinate digest (lactose content of 13.5 g\/kg of protein) at 100, 200, and 400 mg\/kg body weight (BW)\/d were assessed for their effects on the female weaned Wistar rats in terms of daily body weight gain, intestinal morphology, digestive and brush-border enzyme activities, as well as serum chemical indices. The results showed that glycated caseinate digest always showed a weaker effect on rat than caseinate digest either at the 0\u20137 or 0\u201328 d feeding stage, and more importantly, at the highest dose of 400 mg\/kg BW\/d, it caused obvious adverse effect on the rats, reflected by lower values of these indices. Compared with caseinate digest, glycated caseinate digest in the rats caused 0.9\u201315.4% and 10.6\u201349.7% decreases in average daily gain of BW and small intestinal length, 1.1\u201321.5% and 2.3\u201333.3% decreases in villus height and the ratio of villus height to crypt depth of the small intestine, or 0.3\u201357.6% and 0.2\u201355.7% decreases in digestive and critical brush-border enzyme activities, respectively. In addition, when the rats were fed with glycated caseinate digest, some serum indices related to oxidative stress status were enhanced dose-dependently. Lactose glycation of the Maillard-type is thus considered as a negative event of the Maillard reaction on milk proteins because this reaction might impair protein benefits to the body.<\/jats:p>","DOI":"10.3390\/foods10092104","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T21:47:38Z","timestamp":1630964858000},"page":"2104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lactose Glycation of the Maillard-Type Impairs the Benefits of Caseinate Digest to the Weaned Rats for Intestinal Morphology and Serum Biochemistry"],"prefix":"10.3390","volume":"10","author":[{"given":"Xiao-Peng","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China"},{"name":"Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-5426","authenticated-orcid":false,"given":"Xin-Huai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China"},{"name":"School of Biology and Food Engineering, Guangdong University of Petrochemical Technology, Maoming 525000, China"},{"name":"Research Centre of Food Nutrition and Human Healthcare, Guangdong University of Petrochemical Technology, Maoming 525000, China"},{"name":"Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong University of Petrochemical Technology, Maoming 525000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/1541-4337.12178","article-title":"Blocked Lysine in dairy products: Formation, occurrence, analysis, and nutritional implications","volume":"15","author":"Mehta","year":"2016","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gasparini, A., Buhler, S., Faccini, A., Sforza, S., and Tedeschi, T. (2020). Thermally-induced lactosylation of whey proteins: Identification and synthesis of lactosylated \u03b2-lactoglobulin epitope. Molecules, 25.","DOI":"10.3390\/molecules25061294"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3168\/jds.S0022-0302(78)83611-X","article-title":"Interaction of lactose and proteins of skim milk during ultra-high-temperature processing","volume":"61","author":"Turner","year":"1978","journal-title":"J. Dairy Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e126368","DOI":"10.1016\/j.foodchem.2020.126368","article-title":"Maillard reaction products with furan ring, like furosine, cause kidney injury through triggering ferroptosis pathway","volume":"319","author":"Li","year":"2020","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.idairyj.2014.01.017","article-title":"Effect of lactosylation on plasmin-induced hydrolysis of \u03b2-casein","volume":"38","author":"Bhatt","year":"2014","journal-title":"Int. Dairy J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e103308","DOI":"10.1016\/j.jfca.2019.103308","article-title":"Lactose hydrolysis and protein fortification pose an increased risk for the formation of Maillard reaction products in UHT treated milk products","volume":"84","year":"2019","journal-title":"J. Food Compos. Anal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e106822","DOI":"10.1016\/j.foodhyd.2021.106822","article-title":"Utilization of sonication-glycation to improve the functional properties of ovalbumin: A high-resolution mass spectrometry study","volume":"119","author":"Yang","year":"2021","journal-title":"Food Hydrocoll."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yang, H., Zhang, Y., Zhou, F., Guo, J., Tang, J., Han, Y., Li, Z., and Fu, C. (2020). Preparation, bioactivities and applications in food industry of chitosan-based Maillard products: A review. Molecules, 26.","DOI":"10.3390\/molecules26010166"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3164\/jcbn.15-3","article-title":"Advanced glycation end-products: Modifiable environmental factors profoundly mediate insulin resistance","volume":"57","author":"Ottum","year":"2015","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2001049","DOI":"10.1002\/mnfr.202001049","article-title":"New advanced glycation end products observed in rat urine by untargeted metabolomics after feeding with heat-treated skimmed milk powder","volume":"65","author":"Zhou","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/mas.21378","article-title":"Non-enzymatic glycation and glycoxidation protein products in foods and diseases: An interconnected, complex scenario fully open to innovative proteomic studies","volume":"33","author":"Arena","year":"2014","journal-title":"Mass Spectrom. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1053\/j.arrt.2003.08.006","article-title":"Advanced glycation end products in uremia","volume":"10","author":"Henle","year":"2003","journal-title":"Adv. Ren. Replace Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1515\/cclm-2013-0174","article-title":"Glucosepane: A poorly understood advanced glycation end product of growing importance for diabetes and its complications","volume":"52","author":"Monnier","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.kint.2017.11.034","article-title":"Advanced glycation end products in the pathogenesis of chronic kidney disease","volume":"93","author":"Rabbani","year":"2018","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.1021\/acs.jafc.9b01324","article-title":"Effects of protein-derived amino acid modification products present in infant formula on metabolic function, oxidative stress, and intestinal permeability in cell models","volume":"67","author":"Chen","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: Regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1271\/bbb.90730","article-title":"Interaction between food substances and the intestinal epithelium","volume":"74","author":"Shimizu","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jfda.2016.12.003","article-title":"Multifunctions of dietary polyphenols in the regulation of intestinal inflammation","volume":"25","author":"Shimizu","year":"2017","journal-title":"J. Food Drug. Anal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1002\/jsfa.8084","article-title":"Using an enzymatic galactose assay to detect lactose glycation extents of caseinate and soybean protein isolate via the Maillard reaction","volume":"97","author":"Wang","year":"2017","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1039\/C8FO02607F","article-title":"Influence of the Maillard-type caseinate glycation with lactose on the intestinal barrier activity of the caseinate digest in IEC-6 cells","volume":"10","author":"Shi","year":"2019","journal-title":"Food Funct."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.3168\/jds.2016-12491","article-title":"Prior lactose glycation of caseinate via the Maillard reaction affects in vitro activities of the pepsin-trypsin digest toward intestinal epithelial cells","volume":"100","author":"Wang","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_22","unstructured":"AOAC International (2005). Official Methods of Analysis, AOAC International. [18th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.intimp.2017.09.009","article-title":"Anti-inflammatory effect of glucose-lysine Maillard reaction products on intestinal inflammation model in vivo","volume":"52","author":"Hong","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e103729","DOI":"10.1016\/j.jff.2019.103729","article-title":"Potential prebiotic activities of soybean peptides Maillard reaction products on modulating gut microbiota to alleviate aging-related disorders in D-galactose-induced ICR mice","volume":"65","author":"Zhang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/00006676-199305000-00016","article-title":"Simultaneous kinetic determinations of lipase, chymotrypsin, trypsin, elastase, and amylase on the same microtiter plate","volume":"8","author":"Beattie","year":"1993","journal-title":"Pancreas"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1203\/pdr.0b013e3180332c8d","article-title":"Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation","volume":"61","author":"Buccigrossi","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/ajcn\/24.10.1224","article-title":"Alkaline phosphatase and disaccharidase activities in the rat intestine from birth to weaning. I. Effect of diet on enzyme development","volume":"24","author":"Goldstein","year":"1971","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1002\/jsfa.9348","article-title":"Effects of dietary lysozyme levels on growth performance, intestinal morphology, immunity response and microbiota community of growing pigs","volume":"99","author":"Zou","year":"2019","journal-title":"J. Sci. Food Agric."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/1828051X.2020.1747953","article-title":"Effects of dietary supplemented of \u03b3-amino butyric acid on growth performance, blood biochemical indices and intestinal morphology of yellow-feathered broilers exposed to a high temperature environment","volume":"19","author":"Zhong","year":"2020","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3168\/jds.2020-19018","article-title":"Glycation sites and bioactivity of the lactose-glycated caseinate hydrolysate towards the lipopolysaccharide-injured rat intestinal epithelial cells","volume":"104","author":"Shi","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.foodchem.2015.03.038","article-title":"Effects of long-term consumption of standard diets including glucose-lysine model glycated compounds on the antioxidant status of adult rats","volume":"183","author":"Pastoriza","year":"2015","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.fct.2018.12.015","article-title":"Skim milk powder with high content of Maillard reaction products affect weight gain, organ development and intestinal inflammation in early life in rats","volume":"125","author":"Hillman","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2527\/jas.2014-7851","article-title":"Effect of low dosage of chito-oligosaccharide supplementation on intestinal morphology, immune response, antioxidant capacity, and barrier function in weaned piglets","volume":"93","author":"Xiong","year":"2015","journal-title":"J. Anim. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.3382\/ps.2013-03366","article-title":"Effects of a probiotic, Enterococcus faecium, on growth performance, intestinal morphology, immune response, and fecal microflora in broiler chickens challenged with Escherichia coli K88","volume":"92","author":"Cao","year":"2013","journal-title":"Poultry Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6","DOI":"10.14737\/journal.jahp\/2015\/3.1.6.13","article-title":"Flavonoids: Health promoting phytochemicals for animal production-a review","volume":"3","author":"Kamboh","year":"2015","journal-title":"J. Anim. Health Prod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/ajcn\/55.1.299s","article-title":"Physiology and pathophysiology of intestinal absorption","volume":"55","author":"Caspary","year":"1992","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/ps\/76.12.1738","article-title":"Jejunal glucose uptake and oxygen consumption in turkey poults selected for rapid growth","volume":"76","author":"Fan","year":"1997","journal-title":"Poul. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1111\/ijfs.13817","article-title":"Accumulation and effects of dietary advanced glycation end products on the gastrointestinal tract in rats","volume":"53","author":"Yuan","year":"2018","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"164","DOI":"10.17221\/473\/2012-CJFS","article-title":"Maillard product consumption and nitrogen digestibility in young and adult rats","volume":"32","author":"Seiquer","year":"2014","journal-title":"Czech J. Food Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.anifeedsci.2017.11.008","article-title":"Effects of \u03b1-galactosidase supplementation on nutrient digestibility, growth performance, intestinal morphology and digestive enzyme activities in weaned piglets","volume":"236","author":"Shang","year":"2018","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, H., Li, S.S., Fang, S.L., Yang, X.J., and Feng, J. (2018). Betaine improves intestinal functions by enhancing digestive enzymes, ameliorating intestinal morphology, and enriching intestinal microbiota in high-salt stressed rats. Nutrients, 10.","DOI":"10.3390\/nu10070907"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1021\/jf00078a020","article-title":"Effect of Maillard reaction products on protein digestion. Studies on pure compounds","volume":"35","author":"Oste","year":"1987","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/star.201100176","article-title":"Effect of Maillard reaction products prepared from glucose-glycine model systems on starch digestibility","volume":"64","author":"Chung","year":"2012","journal-title":"Starch"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e734513","DOI":"10.1016\/j.aquaculture.2019.734513","article-title":"Effects of glucose-glycine melanoidins on the digestive trypsin-like activity of the rainbow trout oncorhynchus mykiss","volume":"516","author":"Serrano","year":"2019","journal-title":"Aquaculture"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.clnu.2017.03.019","article-title":"Dietary intake of advanced glycation end products is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study","volume":"37","author":"Scheijen","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3109\/09637486.2015.1137889","article-title":"Dietary consumption of advanced glycation end products and risk of metabolic syndrome","volume":"67","author":"Angoorani","year":"2016","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.aquaculture.2018.04.003","article-title":"High stocking density alters growth performance, blood biochemistry, intestinal histology, and muscle quality of channel catfish Ictalurus punctatus","volume":"492","author":"Refaey","year":"2018","journal-title":"Aquaculture"},{"key":"ref_48","first-page":"292","article-title":"Cannabis sativa (Marijuana) alters blood chemistry and the cytoarchitecture of some organs in Sprague Dawley rat models","volume":"16","author":"Abey","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.dsx.2018.11.008","article-title":"The effects of vitamin D supplementation on lipid profiles and oxidative indices among diabetic nephropathy patients with marginal vitamin D status","volume":"13","author":"Barzegari","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e734942","DOI":"10.1016\/j.aquaculture.2020.734942","article-title":"Effects of antioxidant supplementation (nano-selenium, vitamin C and E) on growth performance, blood biochemistry, immune status and body composition of rainbow trout (Oncorhynchus mykiss) under sub-lethal ammonia exposure","volume":"521","author":"Harsij","year":"2020","journal-title":"Aquaculture"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.3382\/ps\/pew227","article-title":"Blood biochemistry, thyroid hormones, and performance in broilers with ascites caused by caffeine","volume":"95","author":"Kamely","year":"2016","journal-title":"Poult. Sci."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/10\/9\/2104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:57:26Z","timestamp":1760165846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/10\/9\/2104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["foods10092104"],"URL":"https:\/\/doi.org\/10.3390\/foods10092104","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]}}}