{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:28:53Z","timestamp":1784903333609,"version":"3.55.0"},"reference-count":39,"publisher":"Informa UK Limited","issue":"10","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The present study was designed to evaluate the hepatoprotective potential of \u03b1-lactalbumin (\u03b1LA) against dimethylnitrosamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in rats by the repeated administration of DMN (10\u00a0mg\/kg, i.p.) on three consecutive days per week for three weeks. The rats were maintained on either a standard AIN-93\u00a0M or \u03b1LA-enriched diet starting one week before the DMN injection until the termination of the experiment. The DMN treatment produced a progressive increase in the plasma markers (aspartate aminotransferase, alanine aminotransferase, total bililbin, hyarulonic acid, and matrix metalloproteinase-2) in 28\u00a0days after the first DMN injection. Dietary treatment with \u03b1LA significantly reduced the DMN-induced damage toward normalcy. N\uff27-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, significantly attenuated the hepatoprotective effect of \u03b1LA. These findings show that \u03b1LA has a marked suppressive effect on hepetic fibrosis through a nitric oxide-mediated mechanism.<\/jats:p>","DOI":"10.1080\/09168451.2017.1356215","type":"journal-article","created":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T10:04:43Z","timestamp":1501236283000},"page":"1941-1947","update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":15,"title":["Bovine milk-derived \u03b1-lactalbumin prevents hepatic fibrosis induced by dimethylnitrosamine via nitric oxide pathway in rats"],"prefix":"10.1080","volume":"81","author":[{"given":"Akika","family":"Fukawa","sequence":"first","affiliation":[{"name":"Food Science Research Labs, R&D Division, Meiji Co., Ltd., Odawara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orie","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Food Science Research Labs, R&D Division, Meiji Co., Ltd., Odawara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Food Science Research Labs, R&D Division, Meiji Co., Ltd., Odawara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Uchida","sequence":"additional","affiliation":[{"name":"Food Science Research Labs, R&D Division, Meiji Co., Ltd., Odawara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hosono","sequence":"additional","affiliation":[{"name":"College of Bioresource Sciences, Nihon University, Fujisawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"301","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"2021033114363121800_CIT0001","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"2021033114363121800_CIT0002","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20071570","article-title":"Liver fibrosis","volume":"411","author":"Wallace","year":"2008","journal-title":"Biochem J"},{"key":"2021033114363121800_CIT0003","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1056\/NEJM199306243282508","article-title":"Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies","volume":"328","author":"Friedman","year":"1993","journal-title":"N Eng J Med"},{"key":"2021033114363121800_CIT0004","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/BF02934504","article-title":"Molecular mechanisms of hepatic fibrosis and principles of therapy","volume":"32","author":"Friedman","year":"1997","journal-title":"J Gastroenterol"},{"key":"2021033114363121800_CIT0005","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1172\/JCI116769","article-title":"Activation-dependent contractility of rat hepatic lipocytes in culture and in vivo","volume":"92","author":"Rockey","year":"1993","journal-title":"J Clin Invest"},{"key":"2021033114363121800_CIT0006","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/S0016-5085(98)70487-1","article-title":"Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension","volume":"114","author":"Rockey","year":"1998","journal-title":"Gastroenterology"},{"key":"2021033114363121800_CIT0007","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1080\/10408690290825574","article-title":"Whey components: millennia of evolution create functionalities for mammalian nutrition: what we know and what we may be overlooking","volume":"42","author":"Walzem","year":"2002","journal-title":"Crit Rev Food Sci Nutr"},{"key":"2021033114363121800_CIT0008","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.nut.2010.04.002","article-title":"Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats","volume":"27","author":"Gad","year":"2011","journal-title":"Nutrition"},{"key":"2021033114363121800_CIT0009","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.3168\/jds.2010-3891","article-title":"Antioxidative effects of whey protein on peroxide-induced cytotoxicity","volume":"94","author":"Xu","year":"2011","journal-title":"J Dairy Sci"},{"key":"2021033114363121800_CIT0010","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1292\/jvms.08-0331","article-title":"Bacteriostatic activity of whey acidic protein (WAP)","volume":"72","author":"Iwamori","year":"2010","journal-title":"J Vet Med Sci"},{"key":"2021033114363121800_CIT0011","doi-asserted-by":"publisher","first-page":"748","DOI":"10.5114\/aoms.2010.17091","article-title":"The use of whey protein concentrate in management of chronic hepatitis C virus\u2014a pilot study","volume":"5","author":"Elattar","year":"2010","journal-title":"Arch Med Sci"},{"key":"2021033114363121800_CIT0012","first-page":"555","article-title":"Dietary whey protein protects against azoxymethane-induced colon tumors in male rats","volume":"10","author":"Hakkak","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2021033114363121800_CIT0013","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1038\/oby.2009.397","article-title":"The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals","volume":"18","author":"Pal","year":"2010","journal-title":"Obesity"},{"key":"2021033114363121800_CIT0014","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1017\/S0007114510005337","article-title":"A whey-based glutathione-enhancing diet decreases allergen-induced airway contraction in a guinea-pig model of asthma","volume":"105","author":"Kloek","year":"2011","journal-title":"Br J Nutr"},{"key":"2021033114363121800_CIT0015","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1271\/bbb.70.1281","article-title":"Hepatoprotective effects of whey protein on d-galactosamine-induced hepatitis and liver fibrosis in rats","volume":"70","author":"Kume","year":"2006","journal-title":"Biosci Biotechnol Biochem"},{"key":"2021033114363121800_CIT0016","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.clnu.2011.10.012","article-title":"A newly designed enteral formula containing whey peptides and fermented milk product protects mice against concanavalin A-induced hepatitis by suppressing overproduction of inflammatory cytokines","volume":"31","author":"Kume","year":"2012","journal-title":"Clin Nutr"},{"key":"2021033114363121800_CIT0017","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/j.nut.2014.02.005","article-title":"Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats","volume":"30","author":"Jobara","year":"2014","journal-title":"Nutrition"},{"key":"2021033114363121800_CIT0018","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1248\/bpb.32.366","article-title":"Novel functions of bovine milk-derived \u03b1-lactalbumin: anti-nociceptive and anti-inflammatory activity caused by inhibiting cyclooxygenase-2 and phospholipase A2","volume":"32","author":"Yamaguchi","year":"2009","journal-title":"Biol Pharm Bull"},{"key":"2021033114363121800_CIT0019","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1080\/09168451.2014.890034","article-title":"Bovine milk-derived \u03b1-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice","volume":"78","author":"Yamaguchi","year":"2014","journal-title":"Biosci Biotechnol Biochem"},{"key":"2021033114363121800_CIT0020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15436\/2377-0902.16.026","article-title":"Protection against dimethylbenz[a] anthracene-induced breast cancer in female rats by \u03b1-lactalbumin","volume":"3","author":"Roy","year":"2016","journal-title":"Int J Cancer Oncol"},{"key":"2021033114363121800_CIT0021","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1248\/bpb.b13-00762","article-title":"Chronic administration of bovine milk-derived \u03b1-lactalbumin improves glucose tolerance via enhancement of adiponectin in Goto-Kakizaki rats with type 2 diabetes","volume":"37","author":"Yamaguchi","year":"2014","journal-title":"Biol Pharm Bull"},{"key":"2021033114363121800_CIT0022","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3168\/jds.S0022-0302(07)71537-0","article-title":"Bovine \u03b1-lactalbumin stimulates mucus metabolism in gastric mucosa","volume":"90","author":"Ushida","year":"2007","journal-title":"J Dairy Sci"},{"key":"2021033114363121800_CIT0023","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s10787-006-1558-9","article-title":"\u03b1-Lactalbumin suppresses interleukin-6 release after intestinal ischemia\/reperfusion via nitric oxide in rats","volume":"15","author":"Yamaguchi","year":"2007","journal-title":"Inflammopharmacology"},{"key":"2021033114363121800_CIT0024","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1111\/hep.2008.38.issue-10","article-title":"Bezafibrate prevents hepatic stellate cell activation and fibrogenesis in a murine steatohepatitis model, and suppresses fibrogenic response induced by transforming growth factor-\u03b21 in a cultured stellate cell line","volume":"38","author":"Nakano","year":"2008","journal-title":"Hepatol Res"},{"key":"2021033114363121800_CIT0025","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0300-483X(90)90064-N","article-title":"Role of metabolism in dimethylnitrosamine-induced immunosuppression: a review","volume":"63","author":"Haggerty","year":"1990","journal-title":"Toxicology"},{"key":"2021033114363121800_CIT0026","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0300-483X(00)00352-8","article-title":"Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen","volume":"156","author":"George","year":"2001","journal-title":"Toxicology"},{"key":"2021033114363121800_CIT0027","doi-asserted-by":"publisher","first-page":"3281","DOI":"10.3168\/jds.2013-7505","article-title":"Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting stellate cell activation","volume":"97","author":"Tung","year":"2014","journal-title":"J Dairy Sci"},{"key":"2021033114363121800_CIT0028","doi-asserted-by":"publisher","first-page":"369","DOI":"10.4162\/nrp.2010.4.5.369","article-title":"Effect of dietary supplementation of grape skin and seeds on liver fibrosis induced by dimethylnitrosamine in rats","volume":"4","author":"Shin","year":"2010","journal-title":"Nutr Res Pract"},{"key":"2021033114363121800_CIT0029","doi-asserted-by":"publisher","first-page":"6142","DOI":"10.3748\/wjg.v12.i38.6142","article-title":"An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine-induced chronic liver injury model in rats","volume":"12","author":"Shin","year":"2006","journal-title":"World J Gastroenterol"},{"key":"2021033114363121800_CIT0030","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1248\/bpb.b15-00328","article-title":"Reduction of dimethylnitrosamine-induced liver fibrosis by the novel gene regulator PI polyamide targeting transforming growth factor \u03b21 gene","volume":"38","author":"Inami","year":"2015","journal-title":"Biol Pharm Bull"},{"key":"2021033114363121800_CIT0031","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/0168-8278(95)80068-9","article-title":"Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats","volume":"23","author":"Nagase","year":"1995","journal-title":"J Hepatol"},{"key":"2021033114363121800_CIT0032","first-page":"599","article-title":"Effect of the nitric oxide donor and the nitric oxide synthase inhibitor on the liver of rats with chronic hepatitis induced by dimethylnitrosamine","volume":"56","author":"Lukivskaya","year":"2004","journal-title":"Pol J Pharmacol"},{"key":"2021033114363121800_CIT0033","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.toxrep.2014.09.001","article-title":"Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow","volume":"1","author":"Amirtharaj","year":"2014","journal-title":"Toxicol Rep"},{"key":"2021033114363121800_CIT0034","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1053\/j.gastro.2003.08.030","article-title":"Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice","volume":"125","author":"McKim","year":"2003","journal-title":"Gastroenterology"},{"key":"2021033114363121800_CIT0035","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1093\/nar\/24.12.2236","article-title":"Inhibition of NF-\u03baB DNA binding by nitric oxide","volume":"24","author":"Matthews","year":"1996","journal-title":"Nucleic Acids Res"},{"key":"2021033114363121800_CIT0036","doi-asserted-by":"publisher","first-page":"14214","DOI":"10.1074\/jbc.270.23.14214","article-title":"Induction and stabilization of I\u03baB\u03b1 by nitric oxide mediates inhibition of NF-\u03baB","volume":"270","author":"Peng","year":"1995","journal-title":"J Biol Chem"},{"key":"2021033114363121800_CIT0037","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cbi.2006.08.021","article-title":"Antiangiogenic effect of lygodium flexuosum against N-nitrosodiethylamine-induced hepatotoxicity in rats","volume":"164","author":"Wills","year":"2006","journal-title":"Chem Biol Interact"},{"key":"2021033114363121800_CIT0038","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1271\/bbb.100599","article-title":"Suppression by fucoidan of liver fibrogenesis via the TGF-\u03b2\/Smad pathway in protecting against oxidative stress","volume":"75","author":"Hong","year":"2011","journal-title":"Biosci Biotechnol Biochem"},{"key":"2021033114363121800_CIT0039","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/jf048626m","article-title":"Preparation of antioxidant enzymatic hydrolysates from \u03b1-lactalbumin and \u03b2-lactoglobulin. Identification of active peptides by HPLC-MS\/MS","volume":"53","author":"Hernandez-Ledesma","year":"2005","journal-title":"J Agric Food Chem"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/81\/10\/1941\/36838528\/bbb1941.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bbb\/article-pdf\/81\/10\/1941\/36838528\/bbb1941.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T11:52:28Z","timestamp":1654602748000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/81\/10\/1941\/5938098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,3]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10,3]]},"published-print":{"date-parts":[[2017,10,3]]}},"URL":"https:\/\/doi.org\/10.1080\/09168451.2017.1356215","relation":{},"ISSN":["0916-8451","1347-6947"],"issn-type":[{"value":"0916-8451","type":"print"},{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,10,3]]},"published":{"date-parts":[[2017,10,3]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=tbbb20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2017-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}