{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:51:08Z","timestamp":1782190268969,"version":"3.54.5"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertensive nephropathy (HN) with progressive renal damage is a common consequence of arterial hypertension (HTN). This study addresses the renoprotective attributes of the sodium-glucose cotransporter-2 inhibitor canagliflozin (Cana) and the dipeptidyl peptidase-4 inhibitor sitagliptin (Sita) on HN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-four adult male Wistar rats were categorized into four groups (six per group): control (CTRL), hypertensive nephropathy (HN); rats were given L-NAME (50 mg\/kg, i.p., once a day), HN + Cana; rats were given L-NAME injections alongside oral Cana 10 mg\/kg, and HN + Sita; rats were provided Sita 10 mg\/kg concurrently with L-NAME injection. All regimens were given once a day for five consecutive weeks. Various physiological, biochemical, molecular, and histological parameters were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Administration of Cana and Sita alleviated HN, as demonstrated by the notable improvements in renal functions, plasma angiotensin II, and systolic blood pressure. Additionally, a noticeable improvement in renal superoxide dismutase, malondialdehyde, NOD-like receptor family pyrin domain containing 3 inflammasome, interleukin (IL)-1\u03b2\/-10, caspase 1, advanced glycation end products (AGEs), and relative expression of receptors for AGEs and nicotinamide adenine dinucleotide phosphate oxidase 4 was detected. Substantial enhancement in the microscopic structure of renal tissues, attenuated renal fibrosis, and decreased immunoreactivity of BAX and tumor necrosis factor-\u03b1 highlighted these protective attributes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both Sita and Cana successfully attenuated HTN and subsequent HN, thereby restoring renal function; however, Sita\u2019s protective profile was more favorable. These results implied that Sita and Cana might provide renoprotective impacts for kidney damage triggered by HTN in rats. However, additional research to investigate their possible modes of action is necessary.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1885144","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:35:52Z","timestamp":1782189352000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The SGLT2i \u201ccanagliflozin\u201d and the DPP-4i \u201csitagliptin\u201d mitigate hypertensive nephropathy in adult male rats by modulating the Ang II\/RAGE\/Nox4\/NLRP3 cascade"],"prefix":"10.3389","volume":"17","author":[{"given":"Fatma E.","family":"Hassan","sequence":"first","affiliation":[{"name":"Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University","place":["Giza, Egypt"]},{"name":"Department of Physiology, General Medicine Practice Program, Batterjee Medical College","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Al-Zahraa Nabil","family":"Al-Shahed","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine for Girls, Al-Azhar University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Selmy","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamiaa Mohamed","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basant A.","family":"Aldreny","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120850","article-title":"LCZ696 (sacubitril\/valsartan) protects against cyclophosphamide-induced nephrotoxicity in adult male rats: Up-regulation of Apelin-13\/ACE2, miR-200, and down-regulation of TGF-\u03b2\/SMAD 2\/3 and miR-192","volume":"306","author":"Abbas","year":"2022","journal-title":"Life Sci."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121654","article-title":"Canagliflozin attenuates thioacetamide-induced liver injury through modulation of HMGB1\/RAGE\/TLR4 signaling pathways","volume":"322","author":"Abdelmageed","year":"2023","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ejphar.2013.10.033","article-title":"Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of L-NAME in rats: Role of GLP-1 and GLP-1 receptor","volume":"720","author":"Abd El Motteleb","year":"2013","journal-title":"Eur. 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