{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:57:02Z","timestamp":1784599022222,"version":"3.55.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"A fund from the Department of Anesthesiology, University of Yamanashi"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background:<\/jats:title>\n                <jats:p>Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods:<\/jats:title>\n                <jats:p>Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5\u00a0m, 15\u00a0m, 30\u00a0m, and 60\u00a0m groups, where lactoferrin (1000\u00a0mg\/kg) was administered enterally 7.5, 15, 30, and 60\u00a0min, respectively, before perfusion; and a control group, where saline was administered 30\u00a0min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15\u00a0mg\/L and 100\u00a0mg\/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20\u00a0min prior to 15\u00a0min of no-flow ischemia with pacing, followed by 20\u00a0min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP\/dt max) 15\u00a0min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results:<\/jats:title>\n                <jats:p>The LV dP\/dt max 15\u00a0min after reperfusion in the E-LF 15 and 30\u00a0m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60\u00a0m group. In the second experiment, there were no significant differences in LV dP\/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion:<\/jats:title>\n                <jats:p>Cardioprotection was observed 15\u201330\u00a0min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-022-00619-w","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T09:03:22Z","timestamp":1665738202000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cardioprotective effects of enteral vs. parenteral lactoferrin administration on myocardial ischemia-reperfusion injury in a rat model of stunned myocardium"],"prefix":"10.1186","volume":"23","author":[{"given":"Keisuke","family":"Omiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Nakadate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Oguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamaki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"619_CR1","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1586\/14779072.2015.1070669","volume":"13","author":"A Binder","year":"2015","unstructured":"Binder A, Ali A, Chawla R, Aziz HA, Abbate A, Jovin IS. Myocardial protection from ischemia-reperfusion injury post coronary revascularization. Expert Rev Cardiovasc Ther. 2015;13:1045\u201357.","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"619_CR2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1177\/1089253211436350","volume":"16","author":"A Frank","year":"2012","unstructured":"Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T. Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth. 2012;16:123\u201332.","journal-title":"Semin Cardiothorac Vasc Anesth"},{"key":"619_CR3","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.jtcvs.2014.11.067","volume":"149","author":"K Maeda","year":"2015","unstructured":"Maeda K, Ruel M. Prevention of ischemia-reperfusion injury in cardiac surgery: therapeutic strategies targeting signaling pathways. J Thorac Cardiovasc Surg. 2015;149:910\u20131.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"619_CR4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1093\/bja\/aep141","volume":"103","author":"J Fr\u00e4ssdorf","year":"2009","unstructured":"Fr\u00e4ssdorf J, De Hert S, Schlack W. Anaesthesia and myocardial ischaemia\/reperfusion injury. Br J Anaesth. 2009;103:89\u201398.","journal-title":"Br J Anaesth"},{"key":"619_CR5","doi-asserted-by":"publisher","first-page":"536510","DOI":"10.1155\/2014\/536510","volume":"2014","author":"T Sato","year":"2014","unstructured":"Sato T, Sato H, Oguchi T, Fukushima H, Carvalho G, Lattermann R, et al. Insulin preconditioning elevates p-Akt and cardiac contractility after reperfusion in the isolated ischemic rat heart. Biomed Res Int. 2014;2014:536510.","journal-title":"Biomed Res Int"},{"key":"619_CR6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12933-017-0527-5","volume":"16","author":"Y Nakadate","year":"2017","unstructured":"Nakadate Y, Sato H, Oguchi T, Sato T, Kawakami A, Ishiyama T, et al. Glycemia and the cardioprotective effects of insulin preconditioning in the isolated rat heart. Cardiovasc Diabetol. 2017;16:43.","journal-title":"Cardiovasc Diabetol"},{"key":"619_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.clnu.2005.02.002","volume":"24","author":"KC Fearon","year":"2005","unstructured":"Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005;24:466\u201377.","journal-title":"Clin Nutr"},{"key":"619_CR8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.clnu.2010.01.004","volume":"29","author":"KK Varadhan","year":"2010","unstructured":"Varadhan KK, Neal KR, Dejong CH, Fearon KC, Ljungqvist O, Lobo DN. The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr. 2010;29:434\u201340.","journal-title":"Clin Nutr"},{"key":"619_CR9","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1016\/j.jtcvs.2018.10.164","volume":"157","author":"JB Williams","year":"2019","unstructured":"Williams JB, McConnell G, Allender JE, Woltz P, Kane K, Smith PK, et al. One-year results from the first US-based enhanced recovery after cardiac surgery (ERAS Cardiac) program. J Thorac Cardiovasc Surg. 2019;157:1881\u20138.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"619_CR10","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1001\/jamasurg.2019.1153","volume":"154","author":"DT Engelman","year":"2019","unstructured":"Engelman DT, Ben Ali W, Williams JB, Perrault LP, Reddy VS, Arora RC, et al. Guidelines for perioperative care in cardiac surgery: enhanced recovery after surgery society recommendations. JAMA Surg. 2019;154:755\u201366.","journal-title":"JAMA Surg"},{"key":"619_CR11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1272\/jnms.84.224","volume":"84","author":"M Sagawa","year":"2017","unstructured":"Sagawa M, Yoshimatsu K, Yokomizo H, Yano Y, Okayama S, Usui T, et al. Worse preoperative status based on inflammation and host immunity is a risk factor for surgical site infections in colorectal cancer surgery. J Nippon Med Sch. 2017;84:224\u201330.","journal-title":"J Nippon Med Sch"},{"key":"619_CR12","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1007\/s00268-012-1590-4","volume":"36","author":"J Vigan\u00f2","year":"2012","unstructured":"Vigan\u00f2 J, Cereda E, Caccialanza R, Carini R, Cameletti B, Spampinato M, et al. Effects of preoperative oral carbohydrate supplementation on postoperative metabolic stress response of patients undergoing elective abdominal surgery. World J Surg. 2012;36:1738\u201343.","journal-title":"World J Surg"},{"key":"619_CR13","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1213\/ANE.0b013e318295e8d1","volume":"117","author":"S Tran","year":"2013","unstructured":"Tran S, Wolever TM, Errett LE, Ahn H, Mazer CD, Keith M. Preoperative carbohydrate loading in patients undergoing coronary artery bypass or spinal surgery. Anesth Analg. 2013;117:305\u201313.","journal-title":"Anesth Analg"},{"key":"619_CR14","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1097\/00000542-200207000-00030","volume":"97","author":"JG Laffey","year":"2002","unstructured":"Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97:215\u201352.","journal-title":"Anesthesiology"},{"key":"619_CR15","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0166-3542(01)00195-4","volume":"52","author":"BW van der Strate","year":"2001","unstructured":"van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res. 2001;52:225\u201339.","journal-title":"Antiviral Res"},{"key":"619_CR16","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.jiac.2014.08.003","volume":"20","author":"H Wakabayashi","year":"2014","unstructured":"Wakabayashi H, Oda H, Yamauchi K, Abe F. Lactoferrin for prevention of common viral infections. J Infect Chemother. 2014;20:666\u201371.","journal-title":"J Infect Chemother"},{"key":"619_CR17","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.ijantimicag.2008.07.020","volume":"33","author":"SA Gonz\u00e1lez-Ch\u00e1vez","year":"2009","unstructured":"Gonz\u00e1lez-Ch\u00e1vez SA, Ar\u00e9valo-Gallegos S, Rasc\u00f3n-Cruz Q. Lactoferrin: structure, function and applications. Int J Antimicrob Agents. 2009;33:e1\u20138.","journal-title":"Int J Antimicrob Agents"},{"key":"619_CR18","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.3390\/molecules24071323","volume":"24","author":"MS Lepanto","year":"2019","unstructured":"Lepanto MS, Rosa L, Paesano R, Valenti P, Cutone A. Lactoferrin in aseptic and septic inflammation. Molecules. 2019;24:1323.","journal-title":"Molecules"},{"key":"619_CR19","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000342633","volume":"49","author":"T Zhang","year":"2012","unstructured":"Zhang T, Wang Y, Ban R, Tong L, Qiao H, Lao H, et al. Oral administration of lactoferrin attenuates intestinal ischemia-reperfusion injury in rats. Eur Surg Res. 2012;49:99\u2013106.","journal-title":"Eur Surg Res"},{"key":"619_CR20","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1002\/acn3.138","volume":"1","author":"Y van de Looij","year":"2014","unstructured":"van de Looij Y, Ginet V, Chatagner A, Toulotte A, Somm E, H\u00fcppi PS, et al. Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain. Ann Clin Transl Neurol. 2014;1:955\u201367.","journal-title":"Ann Clin Transl Neurol"},{"key":"619_CR21","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3390\/ijms20030587","volume":"20","author":"H Li","year":"2019","unstructured":"Li H, Wang Y, Yang H, Liu L, Wang J, Zheng N. Lactoferrin induces the synthesis of vitamin B6 and protects HUVEC functions by activating PDXP and the PI3K\/AKT\/ERK1\/2 pathway. Int J Mol Sci. 2019;20:587.","journal-title":"Int J Mol Sci"},{"key":"619_CR22","doi-asserted-by":"publisher","first-page":"9753","DOI":"10.1038\/s41598-017-10351-9","volume":"7","author":"M Sakai","year":"2017","unstructured":"Sakai M, Matsushita T, Hoshino R, Ono H, Ikai K, Sakai T. Identification of the protective mechanisms of lactoferrin in the irradiated salivary gland. Sci Rep. 2017;7:9753.","journal-title":"Sci Rep"},{"key":"619_CR23","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.amjcard.2006.12.034","volume":"99","author":"H Ishii","year":"2007","unstructured":"Ishii H, Ichimiya S, Kanashiro M, Amano T, Ogawa Y, Mitsuhashi H, et al. Effect of intravenous nicorandil and preexisting angina pectoris on short- and long-term outcomes in patients with a first ST-segment elevation acute myocardial infarction. Am J Cardiol. 2007;99:1203\u20137.","journal-title":"Am J Cardiol"},{"key":"619_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1017\/S0007114510003259","volume":"105","author":"T Ono","year":"2011","unstructured":"Ono T, Morishita S, Fujisaki C, Ohdera M, Murakoshi M, Iida N, et al. Effects of pepsin and trypsin on the anti-adipogenic action of lactoferrin against pre-adipocytes derived from rat mesenteric fat. Br J Nutr. 2011;105:200\u201311.","journal-title":"Br J Nutr"},{"key":"619_CR25","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.yrtph.2008.07.003","volume":"52","author":"D Cerven","year":"2008","unstructured":"Cerven D, DeGeorge G, Bethell D. 28-day repeated dose oral toxicity of recombinant human holo-lactoferrin in rats. Regul Toxicol Pharmacol. 2008;52:174\u20139.","journal-title":"Regul Toxicol Pharmacol"},{"key":"619_CR26","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1113\/expphysiol.2003.026633","volume":"89","author":"T Takeuchi","year":"2004","unstructured":"Takeuchi T, Kitagawa H, Harada E. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats. Exp Physiol. 2004;89:263\u201370.","journal-title":"Exp Physiol"},{"key":"619_CR27","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1093\/jn\/131.8.2101","volume":"131","author":"FJ Troost","year":"2001","unstructured":"Troost FJ, Steijns J, Saris WH, Brummer RJ. Gastric digestion of bovine lactoferrin in vivo in adults. J Nutr. 2001;131:2101\u20134.","journal-title":"J Nutr"},{"key":"619_CR28","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s10534-008-9172-5","volume":"22","author":"P Mladenka","year":"2009","unstructured":"Mladenka P, Semeck\u00fd V, Bobrovov\u00e1 Z, Nachtigal P, V\u00e1vrov\u00e1 J, Holeckov\u00e1 M, et al. The effects of lactoferrin in a rat model of catecholamine cardiotoxicity. Biometals. 2009;22:353\u201361.","journal-title":"Biometals"},{"key":"619_CR29","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1023\/B:BIOM.0000027697.83706.32","volume":"17","author":"S Teraguchi","year":"2004","unstructured":"Teraguchi S, Wakabayashi H, Kuwata H, Yamauchi K, Tamura Y. Protection against infections by oral lactoferrin: evaluation in animal models. Biometals. 2004;17:231\u20134.","journal-title":"Biometals"},{"key":"619_CR30","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1097\/FJC.0b013e318287d526","volume":"61","author":"Y Ikeda","year":"2013","unstructured":"Ikeda Y, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Yoshida S, et al. Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia. J Cardiovasc Pharmacol. 2013;61:423\u20139.","journal-title":"J Cardiovasc Pharmacol"},{"key":"619_CR31","first-page":"1693","volume":"41","author":"G Chang","year":"2018","unstructured":"Chang G, Liu J, Qin S, Jiang Y, Zhang P, Yu H, et al. Cardioprotection by exenatide: a novel m3echanism via improving mitochondrial function involving the GLP-1 receptor\/cAMP\/PKA pathway. Int J Mol Med. 2018;41:1693\u2013703.","journal-title":"Int J Mol Med"},{"key":"619_CR32","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1093\/cvr\/cvs123","volume":"94","author":"S Ravassa","year":"2012","unstructured":"Ravassa S, Zudaire A, D\u00edez J. GLP-1 and cardioprotection: from bench to bedside. Cardiovasc Res. 2012;94:316\u201323.","journal-title":"Cardiovasc Res"},{"key":"619_CR33","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.atherosclerosis.2015.03.026","volume":"240","author":"T Inoue","year":"2015","unstructured":"Inoue T, Inoguchi T, Sonoda N, Hendarto H, Makimura H, Sasaki S, et al. GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats. Atherosclerosis. 2015;240:250\u20139.","journal-title":"Atherosclerosis"},{"key":"619_CR34","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1139\/bcb-2016-0082","volume":"95","author":"Y Maekawa","year":"2017","unstructured":"Maekawa Y, Sugiyama A, Takeuchi T. Lactoferrin potentially facilitates glucose regulation and enhances the incretin effect. Biochem Cell Biol. 2017;95:155\u201361.","journal-title":"Biochem Cell Biol"},{"key":"619_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.15171\/jcvtr.2018.35","volume":"10","author":"S Nozari","year":"2018","unstructured":"Nozari S, Fathi Maroufi N, Nouri M, Paytakhti Oskouei M, Shiralizade J, Yekani F, et al. Decreasing serum homocysteine and hypocholesterolemic effects of Bovine lactoferrin in male rat fed with high-cholesterol diet. J Cardiovasc Thorac Res. 2018;10:203\u20138.","journal-title":"J Cardiovasc Thorac Res"},{"key":"619_CR36","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1271\/bbb.120817","volume":"77","author":"T Ono","year":"2013","unstructured":"Ono T, Fujisaki C, Ishihara Y, Ikoma K, Morishita S, Murakoshi M, et al. Potent lipolytic activity of lactoferrin in mature adipocytes. Biosci Biotechnol Biochem. 2013;77:566\u201371.","journal-title":"Biosci Biotechnol Biochem"},{"key":"619_CR37","doi-asserted-by":"publisher","first-page":"e0141378","DOI":"10.1371\/journal.pone.0141378","volume":"10","author":"K Ikoma-Seki","year":"2015","unstructured":"Ikoma-Seki K, Nakamura K, Morishita S, Ono T, Sugiyama K, Nishino H, et al. Role of LRP1 and ERK and cAMP signaling pathways in lactoferrin-induced lipolysis in mature rat adipocytes. PLoS ONE. 2015;10:e0141378.","journal-title":"PLoS ONE"},{"key":"619_CR38","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1089\/jir.2018.0102","volume":"38","author":"P \u017belechowska","year":"2018","unstructured":"\u017belechowska P, Koz\u0142owska E, Pastwi\u0144ska J, Agier J, Brzezi\u0144ska-B\u0142aszczyk E. Adipocytokine involvement in innate immune mechanisms. J Interferon Cytokine Res. 2018;38:527\u201338.","journal-title":"J Interferon Cytokine Res"},{"key":"619_CR39","doi-asserted-by":"publisher","first-page":"31","DOI":"10.5507\/bp.2017.002","volume":"161","author":"A Smekal","year":"2017","unstructured":"Smekal A, Vaclavik J. Adipokines and cardiovascular disease: a comprehensive review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161:31\u201340.","journal-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub"},{"key":"619_CR40","doi-asserted-by":"publisher","first-page":"E1436","DOI":"10.1152\/ajpendo.00445.2013","volume":"305","author":"Y Zhang","year":"2013","unstructured":"Zhang Y, Wang XL, Zhao J, Wang YJ, Lau WB, Yuan YX, et al. Adiponectin inhibits oxidative\/nitrative stress during myocardial ischemia and reperfusion via PKA signaling. Am J Physiol Endocrinol Metab. 2013;305:E1436\u201343.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"619_CR41","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1093\/cvr\/cvt118","volume":"99","author":"A Jenke","year":"2013","unstructured":"Jenke A, Wilk S, Poller W, Eriksson U, Valaperti A, Rauch BH, et al. Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury. Cardiovasc Res. 2013;99:422\u201331.","journal-title":"Cardiovasc Res"},{"key":"619_CR42","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.3390\/ijms18091985","volume":"18","author":"L Rosa","year":"2017","unstructured":"Rosa L, Cutone A, Lepanto MS, Paesano R, Valenti P. Lactoferrin: a natural glycoprotein involved in iron and inflammatory homeostasis. Int J Mol Sci. 2017;18:1985.","journal-title":"Int J Mol Sci"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-022-00619-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-022-00619-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-022-00619-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T10:07:19Z","timestamp":1665742039000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-022-00619-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["619"],"URL":"https:\/\/doi.org\/10.1186\/s40360-022-00619-w","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]},"assertion":[{"value":"22 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experiments were conducted in accordance with the National Institutes of Health (NIH) guidelines for the care and use of laboratory animals. This study was approved by the Ethics Committee on Animal Research of the University of Yamanashi (Protocol number A 2\u20138, 2020). This study was carried out in compliance with the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}