{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:03:28Z","timestamp":1790363008720,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, driven by oxidative stress, inflammation, and microvascular dysfunction. Dapagliflozin, a selective inhibitor of sodium\u2013glucose cotransporter type 2 (SGLT2), is used in the treatment of type 2 diabetes and has pleiotropic antioxidant and anti-inflammatory effects. The aim of this study was to evaluate the neuroprotective effects of dapagliflozin in an experimental model of streptozotocin (STZ)-induced diabetic peripheral neuropathy in mice. C57BL\/6 mice were divided into three groups: control (DM\u2013), STZ-induced diabetes (DM+), and diabetes + dapagliflozin (DM + DAPA, 10 mg\/kg\/day, oral administration for 12 weeks). Clinical (glycemia, weight, diuresis), electrophysiological, and histopathological parameters were evaluated, and behavioral tests (Open Field, Von Frey, Hot Tail) were performed. Dapagliflozin significantly reduced hyperglycemia, limited weight loss and polyuria, and improved locomotor behavior and nociceptive sensitivity. Electrodiagnostically, the treatment increased the amplitude and reduced the duration of motor potentials, indicating improved nerve conduction. Histological analyses showed decreased hydroxynonenal (HNE) immunoreactivity, suggesting attenuation of oxidative stress, reduced perineural fibrogenesis, and maintained intraepidermal nerve fiber density. Dapagliflozin exerts significant neuroprotective effects in experimental diabetic peripheral neuropathy by reducing oxidative stress, inflammation, and fibrosis and maintaining the structural and functional integrity of peripheral nerves.<\/jats:p>","DOI":"10.3390\/ijms262412034","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy"],"prefix":"10.3390","volume":"26","author":[{"given":"Anca-Maria","family":"\u021auc\u0103","sequence":"first","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"},{"name":"Department of Neurology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Nicoleta","family":"Preda","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgic\u0103","family":"T\u00e2rtea","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"},{"name":"Department of Cardiology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0500-0312","authenticated-orcid":false,"given":"Diana-Ruxandra","family":"H\u0103d\u0103reanu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"\u021aieranu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Oltea","family":"Dan","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena-Anca","family":"T\u00e2rtea","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Gre\u0219i\u021b\u0103","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa Floriana Vasilica","family":"P\u00eer\u0219coveanu","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Sfredel","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-2298","authenticated-orcid":false,"given":"Smaranda Ioana","family":"Mitran","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes. 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