{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:29:11Z","timestamp":1793852951110,"version":"4.6.1"},"reference-count":134,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office\u2014NKFIH","doi-asserted-by":"publisher","award":["K142273"],"award-info":[{"award-number":["K142273"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union, co-financed by the European Social Fund","award":["EFOP-3.6.2-16-2017-00009"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00009"]}],"id":[{"id":"https:\/\/ror.org\/048snh465","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017591","name":"Hungarian Diabetes Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017591","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Diabetic neuropathy is a frequent and disabling complication of diabetes, encompassing distal symmetric polyneuropathy and cardiovascular autonomic neuropathy, both associated with reduced quality of life and increased cardiovascular risk. Beyond its traditional interpretation as a direct consequence of chronic hyperglycaemia, oxidative stress has emerged as a central integrative mechanism linking metabolic overload, inflammation, mitochondrial dysfunction, and microvascular injury to progressive neural damage. These processes converge within the neurovascular unit, promoting a self-perpetuating cycle of axonal degeneration, impaired nerve perfusion and altered neuronal excitability. This narrative review synthesises experimental and clinical evidence on oxidative stress-related pathways implicated in diabetic neuropathy, including hyperglycaemia-activated metabolic routes, mitochondrial dysfunction, endoplasmic reticulum stress, and chronic inflammatory signalling. Classical antioxidant and mitochondrial-supportive interventions are evaluated alongside pleiotropic glucose-lowering agents, with particular emphasis on sodium\u2013glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, integrating mechanistic insights with biomarker and clinical outcome data. Conventional antioxidant strategies, such as \u03b1-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and N-acetylcysteine, show reproducible benefits on neuropathic symptoms and oxidative stress markers, but evidence for sustained structural or disease-modifying effects remains limited. In contrast, incretin-based therapies and sodium\u2013glucose cotransporter-2 inhibitors exert broader pleiotropic actions by attenuating oxidative and inflammatory signalling, improving mitochondrial homeostasis and endothelial function, with emerging evidence for modest but consistent neurophysiological and autonomic benefits. Overall, oxidative stress emerges as a key mechanistic hub in diabetic neuropathy. Future progress will depend on mechanism-aligned, neuropathy-specific clinical trials incorporating multidimensional endpoints and validated biomarkers.<\/jats:p>","DOI":"10.3390\/antiox15030367","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:26:38Z","timestamp":1773393998000},"page":"367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities"],"prefix":"10.3390","volume":"15","author":[{"given":"Ferenc","family":"Sztanek","sequence":"first","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3 Imre","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcell","family":"Herny\u00e1k","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Pet\u0151","sequence":"additional","affiliation":[{"name":"Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Third Department of Internal Medicine, Semmelweis Hospital of Borsod-Abauj-Zemplen County Central Hospital and University Teaching Hospital, H-3515 Miskolc, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5303-3082","authenticated-orcid":false,"given":"Hajnalka","family":"L\u0151rincz","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"Menyh\u00e1rt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra Marietta","family":"Balogh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-7350","authenticated-orcid":false,"given":"Attila Csaba","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, H-4028 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kempler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Paragh","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-9595","authenticated-orcid":false,"given":"Mariann","family":"Harangi","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary"},{"name":"HUN-REN-UD Vascular Pathophysiology Research Group, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41574-021-00496-z","article-title":"Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy","volume":"17","author":"Sloan","year":"2021","journal-title":"Nat. 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