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The animals received 20\u2009mg\/kg ED for 10 days and a single injection of 200\u2009mg\/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal\/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor\u2010alpha, and interleukin 6 (IL\u20106), decreased IL\u201010, and upregulated toll\u2010like receptor 4 (TLR\u20104), nuclear factor\u2010kappa B (NF\u2010\u03baB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR\u20104, NF\u2010\u03baB, JAK1, and STAT3 in CP\u2010induced rats. Treatment with ED upregulated ik\u03b2 kinase \u03b2, IL\u201010, nuclear factor\u2010erythroid 2 related factor 2 (Nrf2), and cytoglobin,\u00a0and boosted glutathione, superoxide dismutase, and glutathione S\u2010transferase. Molecular docking simulations revealed the ability of ED to bind TLR\u20104, NF\u2010\u03baB, JAK1, and STAT3. <jats:italic>In vitro<\/jats:italic>, ED increased the cytotoxic activity of CP against HeLa, Caco\u20102, and K562 cell lines. In conclusion, ED prevented CP\u2010induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR\u20104\/NF\u2010\u03baB, and JAK1\/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.<\/jats:p>","DOI":"10.1002\/jbt.22889","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T08:20:23Z","timestamp":1628842823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR\u20104\/NF\u2010\u03baB, and JAK1\/STAT3 signaling in cyclophosphamide\u2010intoxicated rats"],"prefix":"10.1002","volume":"35","author":[{"given":"Emad H. 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