{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:28:10Z","timestamp":1760059690757,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\u2014FCT\/MCTES","award":["UIDP\/50006\/2020","2020.06502.BD","10.54499\/2020.06502.BD"],"award-info":[{"award-number":["UIDP\/50006\/2020","2020.06502.BD","10.54499\/2020.06502.BD"]}]},{"name":"FCT PhD scholarship","award":["UIDP\/50006\/2020","2020.06502.BD","10.54499\/2020.06502.BD"],"award-info":[{"award-number":["UIDP\/50006\/2020","2020.06502.BD","10.54499\/2020.06502.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastrointestinal (GI) complications are common in diabetes, but the role of the local renin-angiotensin-aldosterone system (RAAS) in gut remodeling remains unclear. This study examined histomorphometric alterations, oxidative stress, and systemic and tissue-specific angiotensin converting enzyme (ACE) and ACE2 activity in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats (n = 24) were assigned to control (CTRL), diabetic (STZ), and diabetic groups treated with losartan (STZ-LOS, 20 mg\/kg\/day) or finerenone (STZ-FIN, 10 mg\/kg\/day). After 14 days, gut samples were collected from the stomach, duodenum, jejunum, ileum, and colon for histology, glutathione measurements (GSH\/GSSG), and ACE\/ACE2 activity assessment. Diabetic rats exhibited increased GI wall thickness\u2014particularly in the mucosal and muscular layers\u2014elevated GSSG levels, and a reduced GSH\/GSSG ratio. Losartan prevented these changes, whereas finerenone did not produce a significant effect. Circulating ACE and ACE2 levels were elevated, but the ACE2\/ACE ratio remained unchanged. Locally, ACE activity increased across gut segments, whereas ACE2 remained stable, lowering the ACE2\/ACE ratio, particularly in the duodenum and jejunum. The Z-FHL\/h-HL ratio was above 1 across segments but decreased in these same regions (jejunum and duodenum). These findings highlight the protective role of losartan against diabetic GI remodeling via AT1R blockade and suggest complex, segment-specific RAAS regulation in diabetic gut pathology.<\/jats:p>","DOI":"10.3390\/ijms26136294","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Effects of Losartan and Finerenone on Diabetic Remodeling, Oxidative Stress and ACE Activity in the Gastrointestinal Tract of Streptozotocin-Induced Diabetic Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0585-3905","authenticated-orcid":false,"given":"Marisa","family":"Esteves-Monteiro","sequence":"first","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV@REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Immuno-Physiology and Pharmacology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal"}]},{"given":"Cl\u00e1udia","family":"Vitorino-Oliveira","sequence":"additional","affiliation":[{"name":"Institute for Health and Bioeconomy (i4HB), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal"},{"name":"Applied Molecular Biosciences Unit (UCIBIO), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5585-7446","authenticated-orcid":false,"given":"Joana","family":"Castanheira-Moreira","sequence":"additional","affiliation":[{"name":"Department of Immuno-Physiology and Pharmacology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"given":"Mariana","family":"Ferreira-Duarte","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV@REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-794X","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Dias-Pereira","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV@REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS-UP, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-2756","authenticated-orcid":false,"given":"Vera Marisa","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute for Health and Bioeconomy (i4HB), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal"},{"name":"Applied Molecular Biosciences Unit (UCIBIO), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-0613","authenticated-orcid":false,"given":"Manuela","family":"Morato","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV@REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-727X","authenticated-orcid":false,"given":"Margarida","family":"Duarte-Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV@REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Immuno-Physiology and Pharmacology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2016). 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