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- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005)
- Serena Boccella, Andrea Maria Morace, Cristina Giorgio, Francesca Guida, Michela Perrone, Iolanda Manzo, Carmela Belardo, Meghan Jones, Sabatino Maione, Andrea Aramini, Marcello Allegretti, Livio Luongo, Laura Brandolini
- Diabetes Metab J. 2026;50(3):626-627. Published online April 30, 2026
- DOI: https://doi.org/10.4093/dmj.2026.0036
- 419 View
- 12 Download
- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005)
- Serena Boccella, Andrea Maria Morace, Cristina Giorgio, Francesca Guida, Michela Perrone, Iolanda Manzo, Carmela Belardo, Meghan Jones, Sabatino Maione, Andrea Aramini, Marcello Allegretti, Livio Luongo, Laura Brandolini
- Diabetes Metab J. 2025;49(6):1356-1357. Published online November 1, 2025
- DOI: https://doi.org/10.4093/dmj.2025.0927
- 1,745 View
- 24 Download
Original Article
- Basic and Translational Research
- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat
- Serena Boccella, Andrea Maria Morace, Cristina Giorgio, Francesca Guida, Michela Perrone, Iolanda Manzo, Carmela Belardo, Meghan Jones, Sabatino Maione, Andrea Aramini, Marcello Allegretti, Livio Luongo, Laura Brandolini
- Diabetes Metab J. 2025;49(5):990-1005. Published online March 12, 2025
- DOI: https://doi.org/10.4093/dmj.2024.0504
- 5,968 View
- 254 Download
- 7 Web of Science
- 3 Crossref
-
Abstract
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PubReader 
ePub - Background
The CXC motif chemokine ligand 8 (CXCL8)-CXC motif chemokine receptor 1/2 (CXCR1/2) axis has been implicated in type 1 diabetes mellitus (T1DM). Its actions on non-immune cells may also contribute to T1DM-associated complications, including painful diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR).
Methods
We assessed the efficacy of early (4–8 weeks) or late (8–12 weeks) daily ladarixin (LDX) for the treatment of streptozotocin (STZ)-induced T1DM and the related complications of DPN or DR in male rats.
Results
Early LDX mitigated STZ-induced dysmetabolism (i.e., blood glucose, insulin), inflammation in dorsal root ganglion/ sciatic nerve (interleukin-1β and tumor necrosis factor-α expression) and mechanical allodynia and thermal hyperalgesia, indicative of DPN. Moreover, vitreous citrullinated histone H3 (CitH3) and plasma GRO/CINC1 (CXCL8) increase were attenuated. Late LDX failed to reverse STZ-induced changes in metabolic parameters (i.e., blood glucose, insulin, C-peptide, pancreatic β-cell number and function). Strikingly, even in the absence of an effect on glycemic control, late LDX mitigated STZ-induced mechanical allodynia and thermal hyperalgesia and vitreous (CXCL8, CitH3) and retinal (CXCL8, CXCR1/2, myeloperoxidase, CitH3) inflammatory/pro-angiogenic (vascular endothelial growth factor, CD34) signs of DR.
Conclusion
These data confirm the efficacy of LDX in STZ-induced T1DM and provide evidence of a protective effect also against DPN and onset of DR which is independent of its effect on β-cell functionality preservation and glycemic control. -
Citations
Citations to this article as recorded by
- New pharmacological agents and emerging therapeutic targets for painful diabetic neuropathy
Theodoros Panou, Nikolaos Papanas, Peter Kempler
Frontiers in Endocrinology.2026;[Epub] CrossRef - Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes
Georgia Fousteri, Meghan Jones, Rubina Novelli, Serena Boccella, Laura Brandolini, Andrea Aramini, Paolo Pozzilli, Marcello Allegretti
Frontiers in Immunology.2025;[Epub] CrossRef - Ladarixin Potential over the Effects of IL-8 and of Serum from Patients with Abdominal Aortic Aneurysm on Human Aortic Cells
Lucia Spartano, Maria Lombardi, Vincenzo Ardita, Roberto Chiesa, Andrea Aramini, Marcello Allegretti, Domenico Baccellieri, Lidia De Filippis, Chiara Foglieni
Cells.2025; 14(21): 1713. CrossRef
- New pharmacological agents and emerging therapeutic targets for painful diabetic neuropathy
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