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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy

by
Anca-Maria Țucă
1,2,
Alexandra Nicoleta Preda
1,
Georgică Târtea
1,3,*,
Diana-Ruxandra Hădăreanu
3,
Eugen Țieranu
3,
Alexandra Oltea Dan
1,
Elena-Anca Târtea
2,
Andrei Greșiță
1,
Denisa Floriana Vasilica Pîrșcoveanu
2,
Veronica Sfredel
1 and
Smaranda Ioana Mitran
1
1
Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 2 Petru Rares Street, 200349 Craiova, Romania
2
Department of Neurology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania
3
Department of Cardiology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares St., 200349 Craiova, Romania
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(24), 12034; https://doi.org/10.3390/ijms262412034
Submission received: 11 November 2025 / Revised: 10 December 2025 / Accepted: 12 December 2025 / Published: 14 December 2025
(This article belongs to the Section Molecular Pharmacology)
Versions Notes

Abstract

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–glucose 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–), 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.
Keywords: dapagliflozin; diabetes mellitus; diabetic peripheral neuropathy; oxidative stress; neuroprotection dapagliflozin; diabetes mellitus; diabetic peripheral neuropathy; oxidative stress; neuroprotection

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MDPI and ACS Style

Țucă, A.-M.; Preda, A.N.; Târtea, G.; Hădăreanu, D.-R.; Țieranu, E.; Dan, A.O.; Târtea, E.-A.; Greșiță, A.; Pîrșcoveanu, D.F.V.; Sfredel, V.; et al. Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy. Int. J. Mol. Sci. 2025, 26, 12034. https://doi.org/10.3390/ijms262412034

AMA Style

Țucă A-M, Preda AN, Târtea G, Hădăreanu D-R, Țieranu E, Dan AO, Târtea E-A, Greșiță A, Pîrșcoveanu DFV, Sfredel V, et al. Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy. International Journal of Molecular Sciences. 2025; 26(24):12034. https://doi.org/10.3390/ijms262412034

Chicago/Turabian Style

Țucă, Anca-Maria, Alexandra Nicoleta Preda, Georgică Târtea, Diana-Ruxandra Hădăreanu, Eugen Țieranu, Alexandra Oltea Dan, Elena-Anca Târtea, Andrei Greșiță, Denisa Floriana Vasilica Pîrșcoveanu, Veronica Sfredel, and et al. 2025. "Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy" International Journal of Molecular Sciences 26, no. 24: 12034. https://doi.org/10.3390/ijms262412034

APA Style

Țucă, A.-M., Preda, A. N., Târtea, G., Hădăreanu, D.-R., Țieranu, E., Dan, A. O., Târtea, E.-A., Greșiță, A., Pîrșcoveanu, D. F. V., Sfredel, V., & Mitran, S. I. (2025). Dapagliflozin Preserves Peripheral Nerve Structure and Reduces Neuropathic Damage in Streptozotocin-Induced Diabetic Peripheral Neuropathy. International Journal of Molecular Sciences, 26(24), 12034. https://doi.org/10.3390/ijms262412034

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