{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:12:16Z","timestamp":1789686736396,"version":"4.0.1"},"reference-count":27,"publisher":"Pharmaceutical Society of Japan","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological & Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2015]]},"DOI":"10.1248\/bpb.b14-00847","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T18:05:40Z","timestamp":1430417140000},"page":"746-752","source":"Crossref","is-referenced-by-count":26,"title":["In a Methotrexate-Induced Model of Intestinal Mucositis, Olmesartan Reduced Inflammation and Induced Enteropathy Characterized by Severe Diarrhea, Weight Loss, and Reduced Sucrose Activity"],"prefix":"10.1248","volume":"38","author":[{"given":"Aurigena Antunes","family":"de Ara\u00fajo","sequence":"first","affiliation":[{"name":"Department of Biophysics and Pharmacology, Federal University of Rio Grande Norte (UFRN), Post Graduation Program Public Health\/Post Graduation Program in Pharmaceutical Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Brito","family":"Borba","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Henrique Destefani","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Medicine, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u00e1lia Cristina","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Medicine, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta\u00eds Suassuna","family":"Saldanha","sequence":"additional","affiliation":[{"name":"Department of Medicine, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thayse Emanuele Franklin","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Medicine, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldemara Ingrid","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo Fernandes","family":"de Ara\u00fajo J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Morphology, Post Graduation Program Health Science\/Post Graduation Program in Functional and Structural Biology, UFRN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Alamir I, Boukhettala N, Aziz M, Breuille D, Dechelotte P, Coeffier M. Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis. Clin. Exp. Immunol.<\/i>, 162<\/b>, 298\u2013305 (2010).","DOI":"10.1111\/j.1365-2249.2010.04220.x"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Duncan M, Grant G. Oral and intestinal mucositis-causes and possible treatments. Aliment. Pharmacol. Ther.<\/i>, 18<\/b>, 853\u2013874 (2003).","DOI":"10.1046\/j.1365-2036.2003.01784.x"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Stringer AM. Interaction between host cells and microbes in chemotherapy-induced mucositis. Nutrients<\/i>, 5<\/b>, 1488\u20131499 (2013).","DOI":"10.3390\/nu5051488"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) van Vliet MJ, Harmsen HJM, de Bont ESJM, Tissing WJE. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog.<\/i>, 6<\/b>, e1000879 (2010).","DOI":"10.1371\/journal.ppat.1000879"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Sezer A, Usta U, Cicin I. The effect of Saccharomyces boulardii<\/i> on reducing irinotecan-induced intestinal mucositis and diarrhea. Med. Oncol.<\/i>, 26<\/b>, 350\u2013357 (2009).","DOI":"10.1007\/s12032-008-9128-1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB. Perspectives on cancer therapy-induced mucosal injury\u2014Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer<\/i>, 100<\/b> (Suppl.), 1995\u20132025 (2004).","DOI":"10.1002\/cncr.20162"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Keefe DMK, Brealey J, Goland GJ, Cummins AG. Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut<\/i>, 47<\/b>, 632\u2013637 (2000).","DOI":"10.1136\/gut.47.5.632"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Gibson RJ, Bowen JM, Inglis MRB, Cummins AG, Keefe DMK. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J. Gastroenterol. Hepatol.<\/i>, 18<\/b>, 1095\u20131100 (2003).","DOI":"10.1046\/j.1440-1746.2003.03136.x"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DMK. Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother. Pharmacol.<\/i>, 62<\/b>, 33\u201341 (2008).","DOI":"10.1007\/s00280-007-0570-0"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Tooley KL, Howarth GS, Lymn KA, Lawrence A, Butler RN. Oral ingestion of streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats. Cancer Biol. Ther.<\/i>, 5<\/b>, 593\u2013600 (2006).","DOI":"10.4161\/cbt.5.6.2659"},{"key":"11","unstructured":"11) Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Annals of Oncology: Official Journal of the European Society for Medical Oncology\/ESMO<\/i>, 22<\/b> (Suppl. 6), 78\u201384 (2011)."},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Mire DE, Silfani TN, Pugsley MK. A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker. J. Cardiovasc. Pharmacol.<\/i>, 46<\/b>, 585\u2013593 (2005).","DOI":"10.1097\/01.fjc.0000180902.78230.fd"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Ara\u00fajo AA, Lopes de Souza G, Souza TO, de Castro Brito GA, Sab\u00f3ia Arag\u00e3o K, Xavier de Medeiros CA, Louren\u00e7o Y, do Socorro Costa Feitosa Alves M, Fernandes de Ara\u00fajo R Jr. Olmesartan decreases IL-1beta and TNF-alpha levels; downregulates MMP-2, MMP-9, COX-2, and RANKL; and upregulates OPG in experimental periodontitis. Naunyn Schmiedebergs Arch. Pharmacol.<\/i>, 386<\/b>, 875\u2013884 (2013).","DOI":"10.1007\/s00210-013-0886-8"},{"key":"14","unstructured":"14) Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, Yokoi T, Kamataki T. Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res.<\/i>, 56<\/b>, 3752\u20133757 (1996)."},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Souza MH, Troncon LE, Cunha FQ, Oliveira RB. Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats. Braz. J. Med. Biol. Res.<\/i>, 36<\/b>, 1383\u20131390 (2003).","DOI":"10.1590\/S0100-879X2003001000015"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ. Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Br. J. Pharmacol.<\/i>, 115<\/b>, 1265\u20131275 (1995).","DOI":"10.1111\/j.1476-5381.1995.tb15035.x"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Kendall C, Ionescu-Matiu I, Dreesman GR. Utilization of the biotin\/avidin system to amplify the sensitivity of the enzyme-linked immunosorbent assay (ELISA). J. Immunol. Methods<\/i>, 56<\/b>, 329\u2013339 (1983).","DOI":"10.1016\/S0022-1759(83)80022-2"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Kolli VK, Kanakasabapathy I, Faith M, Ramamoorthy H, Isaac B, Natarajan K, Abraham P. A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation. Cancer Chemother. Pharmacol.<\/i>, 71<\/b>, 1209\u20131218 (2013).","DOI":"10.1007\/s00280-013-2115-z"},{"key":"19","unstructured":"19) Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Annals of Oncology: Official Journal of the European Society for Medical Oncology\/ESMO<\/i>, 21<\/b> (Suppl. 5), 261\u2013265 (2010)."},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Soares PM, Lopes LO, Mota JM, Belarmino-Filho JN, Ribeiro RA, Souza MH. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats. Arq. Gastroenterol.<\/i>, 48<\/b>, 80\u201385 (2011).","DOI":"10.1590\/S0004-28032011000100016"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Tooley KL, Howarth GS, Butler RN. Mucositis and non-invasive markers of small intestinal function. Cancer Biol. Ther.<\/i>, 8<\/b>, 753\u2013758 (2009).","DOI":"10.4161\/cbt.8.9.8232"},{"key":"22","unstructured":"22) Sultani M, Stringer AM, Bowen JM, Gibson RJ. Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemother. Res. Pract.<\/i>, 2012<\/b>, 490804 (2012)."},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Pink IJ. Diarrhoea due to sucrase and isomaltase deficiency. Gut<\/i>, 8<\/b>, 373\u2013376 (1967).","DOI":"10.1136\/gut.8.4.373"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Gray GM, Santiago NA. Disaccharide absorption in normal and diseased human intestine. Gastroenterology<\/i>, 51<\/b>, 489\u2013498 (1966).","DOI":"10.1016\/S0016-5085(19)34364-1"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Rubio-Tapia A, Herman ML, Ludvigsson JF, Kelly DG, Mangan TF, Wu TT, Murray JA. Severe spruelike enteropathy associated with olmesartan. Mayo Clin. Proc.<\/i>, 87<\/b>, 732\u2013738 (2012).","DOI":"10.1016\/j.mayocp.2012.06.003"},{"key":"26","unstructured":"26) FDA. U.S.A. \u201cFDA Drug Safety Communication: FDA approves label changes to include intestinal problems (sprue-like enteropathy) linked to blood pressure medicine olmesartan medoxomil.\u201d U.S.A., 2013."},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Uil JJ, van Elburg RM, van Overbeek FM, Meyer JW, Mulder CJ, Heymans HS. Follow-up of treated coeliac patients: sugar absorption test and intestinal biopsies compared. Eur. J. Gastroenterol. Hepatol.<\/i>, 8<\/b>, 219\u2013223 (1996).","DOI":"10.1097\/00042737-199603000-00006"}],"container-title":["Biological & Pharmaceutical Bulletin","Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/38\/5\/38_b14-00847\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,24]],"date-time":"2019-08-24T06:59:37Z","timestamp":1566629977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/38\/5\/38_b14-00847\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b14-00847","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015]]}}}