{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:39:02Z","timestamp":1772159942009,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T00:00:00Z","timestamp":1602979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID\u2010induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti\u2010inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30\u00a0mg\/kg of lansoprazole), SIL 5 (5\u00a0mg\/kg), SIL 25 (25\u00a0mg\/kg) and SIL 50 (50\u00a0mg\/kg). The animals were treated by gavage (a single dose) after 24\u00a0hours of fasting, and gastric lesions were performed after 30\u00a0minutes, with indomethacin (40\u00a0mg\/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose\u2010dependent gastroprotective effect against NSAID\u2010induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin\u2010induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.<\/jats:p>","DOI":"10.1111\/1440-1681.13414","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T22:17:02Z","timestamp":1601936222000},"page":"401-411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sildenafil attenuates nonsteroidal anti\u2010inflammatory\u2010induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms"],"prefix":"10.1111","volume":"48","author":[{"given":"Gisele","family":"Maziero Alves","sequence":"first","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-9401","authenticated-orcid":false,"given":"Rafaela","family":"Aires","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology Health Sciences Center Federal University of Espirito Santo (UFES) Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f4nica","family":"de Souza Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Zambom C\u00f4co","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Peters","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ar\u00edcia","family":"de Leone Evangelista Monteiro Assis","sequence":"additional","affiliation":[{"name":"Department of Morphology Health Sciences Center Federal University of Espirito Santo Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brena","family":"Ramos Athaydes","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences Department of Pharmaceutical Sciences Federal University of Espirito Santo Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Gobbi Amorim","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breno","family":"Valentim Nogueira","sequence":"additional","affiliation":[{"name":"Department of Morphology Health Sciences Center Federal University of Espirito Santo Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita C\u00e1ssia","family":"de Ribeiro Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences Department of Pharmaceutical Sciences Federal University of Espirito Santo Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"dos Santos Meyrelles","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology Health Sciences Center Federal University of Espirito Santo (UFES) Vitoria Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"Melo Costa Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"},{"name":"Federal Institute of Education, Science and Technology (IFES) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Prandi Campagnaro","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Physiology and Pharmacology Pharmaceutical Sciences Graduate Program Vila Velha University (UVV) Vila Velha Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cali.2015.06.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.03.054"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2018.10.057"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10068-018-0342-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12255"},{"key":"e_1_2_8_7_1","first-page":"255","article-title":"Gastrointestinal damage by non\u2010steroidal anti\u2010inflammatory drugs: updated clinical considerations","volume":"60","author":"Pellicano R","year":"2014","journal-title":"Minerva Gastroenterol Dietol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.20452\/pamw.2715","article-title":"New insight into the mechanisms of gastroduodenal injury induced by nonsteroidal anti\u2010inflammatory drugs: practical implications","volume":"125","author":"Kwiecien S","year":"2015","journal-title":"Pol Arch Med Wewn"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9514703"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2015.03.006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.02.070"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.117"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.7193"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9050521"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124653"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280490"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v5.i1.40"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.075"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706361"},{"key":"e_1_2_8_20_1","first-page":"179","article-title":"Sildenafil citrate protects against gastric mucosal damage induced by indomethacin in rats","volume":"17","author":"Moustafa YM","year":"2013","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2012"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.5772\/17640"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666180629111227"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2002000500003"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i45.17020"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2015.07.002"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00162-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-008-0266-2"},{"key":"e_1_2_8_29_1","first-page":"157","article-title":"Nonsteroidal anti\u2010inflammatory drugs (NSAID) sparing effects of glucosamine hydrochloride through N\u2010glycosylation inhibition; strategy to rescue stomach from NSAID damage","volume":"64","author":"Park SH","year":"2013","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.04.022"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-013-9594-y"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-35"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000485817"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2011.01268.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201017666151223123904"},{"key":"e_1_2_8_36_1","first-page":"47","article-title":"Sildenafil: an orally active type 5 cyclic GMP\u2010specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction","volume":"8","author":"Boolell M","year":"1996","journal-title":"Int J Impot Res"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707605"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-008-0646-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.08.013"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4257(01)00007-9"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201019666180625094704"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2005.05643.x"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706305"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122417"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24030622"},{"key":"e_1_2_8_46_1","first-page":"268","article-title":"The role of sildenafil citrate in the protection of gastric mucosa from nonsteroidal anti\u2010inflammatory drug\u2010induced damage","volume":"13","author":"Aydinli B","year":"2007","journal-title":"Ulus Travma Acil Cerrahi Derg"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00355.2012"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2002.012930"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt231"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-12-128"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2008.10.004"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2019.1572887"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.02.001"},{"key":"e_1_2_8_54_1","first-page":"265","article-title":"The production of acute gastric ulceration by indomethacin in the rat","volume":"4","author":"Djahanguiri B","year":"1969","journal-title":"Scand J Gastroenterol"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.02.049"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00572.x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.08.035"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.186"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-018-0182-7"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.06.032"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1440-1681.13414","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T10:40:02Z","timestamp":1723718402000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.13414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,18]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/1440-1681.13414"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.13414","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/1440-1681.13414\/v1\/review2","asserted-by":"object"}]},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,18]]},"assertion":[{"value":"2020-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}