{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:53:28Z","timestamp":1791928408671,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006472","name":"Grigore T. Popa University of Medicine and Pharmacy","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006472","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03hd30t45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Diabetic kidney disease is a common and serious complication of type 2 diabetes mellitus (T2DM) and represents a major contributor to chronic kidney disease (CKD) globally. While sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant renoprotective effects, the potential advantages of combining these agents with micronutrients such as zinc (Zn), known for its antioxidant, anti-inflammatory, and metabolic regulatory properties, have not been fully investigated. This study aimed to assess the effects of dapagliflozin (DAPA) and empagliflozin (EMPA), administered either alone or alongside Zn, in an experimental diabetes model. Methods: T2DM was induced in Sprague-Dawley rats through a high-fat diet (HFD) followed by a low dose of streptozotocin (STZ). Seven experimental groups were established: a control group, an untreated diabetic group, and treatment groups receiving DAPA, EMPA, or their combinations with Zn. Metabolic parameters, renal function, and histopathological alterations were assessed, while immunohistochemistry was used to evaluate the expression of inflammatory and fibrotic markers. Results: Diabetic rats exhibited sustained hyperglycemia, metabolic imbalance, and significant renal damage, accompanied by elevated levels of inflammatory and fibrotic markers. Treatment with SGLT2 inhibitors improved metabolic status, mitigated kidney injury, and reduced inflammatory marker expression. Zn association further potentiated these effects, with the most pronounced benefits observed when combined with EMPA. Conclusions: These findings suggest that SGLT2 inhibitors exert strong renoprotective effects in experimental diabetic nephropathy. Zn supplementation may amplify these benefits through its antioxidant and anti-inflammatory actions. The combination of EMPA and Zn demonstrated the greatest protective effect, highlighting the potential of multi-target therapeutic strategies in diabetic kidney disease.<\/jats:p>","DOI":"10.3390\/life16050793","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:32:28Z","timestamp":1779676348000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Zinc Potentiates the Renoprotective Effects of SGLT2 Inhibitors in Experimental Diabetes Mellitus in Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1603-8272","authenticated-orcid":false,"given":"Irina Claudia","family":"Anton","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-0296","authenticated-orcid":false,"given":"Carmen","family":"Solcan","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, Aleea Mihail Sadoveanu No. 3, 700490 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-3811","authenticated-orcid":false,"given":"Liliana","family":"Mititelu Tartau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-104X","authenticated-orcid":false,"given":"Cornelia","family":"Amalinei","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-2748","authenticated-orcid":false,"given":"Mihaela","family":"Poroch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-5395","authenticated-orcid":false,"given":"Vladimir","family":"Poroch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-5478","authenticated-orcid":false,"given":"Beatrice Rozalina","family":"Buca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-5782","authenticated-orcid":false,"given":"Cosmin-Gabriel","family":"Tartau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-3780","authenticated-orcid":false,"given":"Ana-Maria","family":"Pelin","sequence":"additional","affiliation":[{"name":"Department of Morphological and Functional Sciences, Dunarea de Jos University,  800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-1127","authenticated-orcid":false,"given":"Gina Eosefina","family":"Botnariu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii St. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"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 Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. 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