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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\u20138 weeks) or late (8\u201312 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-1\u03b2 and tumor necrosis factor-\u03b1 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 \u03b2-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 \u03b2-cell functionality preservation and glycemic control.<\/jats:p>","DOI":"10.4093\/dmj.2024.0504","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:50:53Z","timestamp":1741751453000},"page":"990-1005","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of CXCR1\/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in 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