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High mobility group box 1 (HMGB\u20101) protein, which induces inflammation through the aberrant stimulation of the Toll\u2010like receptor 4 (TLR4)\/myeloid differentiation primary response protein (MyD88)\/nuclear factor kappa B (NF\u2010\u03baB) trajectory, could represent a molecular target for alleviating Tac\u2010induced renal damage. The present study aimed to investigate the potential protective role of the GLP\u20101 agonist, dulaglutide (Dula), against Tac\u2010induced nephrotoxicity in rats. Rats were administered Tac (5\u2009mg\/kg\/day) and vehicle or Dula (0.2\u2009mg\/kg once a week) for 14 days. Treatment with Dula reduced serum creatinine plus blood urea nitrogen and attenuated Tac\u2010induced renal histopathological changes. Dula treatment also hampered renal inflammation and restored redox homeostasis, as indicated by remarkably reduced tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), interleukin\u20101\u03b2 (IL\u20101\u03b2), malondialdehyde (MDA), and NADPH oxidase 1 levels alongside marked replenishment in reduced glutathione (GSH) content. These effects were mediated through the upregulation of miR\u201022 expression and the consequent inhibition of the HMGB\u20101\/TLR4\/MyD88\/NF\u2010\u03baB trajectory. Collectively, Dula has been demonstrated to protect rats against Tac\u2010induced nephrotoxicity by reducing inflammation, restoring redox homeostasis, and modulation of the miR\u201022\/HMGB\u20101\/TLR4\/MyD88\/NF\u2010\u03baB trajectory. Dula may be beneficial clinically in preventing Tac\u2010induced renal injury.<\/jats:p>","DOI":"10.1002\/ardp.202500023","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:28:46Z","timestamp":1744270126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus\u2010Induced Nephrotoxicity Through Targeting the miR\u201022\/HMGB\u20101\/TLR4\/MyD88\/NF\u2010\u03baB Trajectory"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-8525","authenticated-orcid":false,"given":"Rasha","family":"Abdelhady","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Fayoum University  Fayoum Egypt"},{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Egyptian Chinese University  Cairo 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