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Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF\u2010\u03baB\/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti\u2010inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200\u2009mg\/kg\/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight\/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO\u20101 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF\u2010\u03baB signaling and its consequent target pro\u2010inflammatory mediators, IL\u20106 and TNF\u2010\u03b1. In contrast, IL\u201010 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti\u2010inflammatory, antioxidant, and antiapoptotic properties.<\/jats:p>","DOI":"10.1096\/fj.202200749r","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T11:00:05Z","timestamp":1660129205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Ambroxol, a mucolytic agent, boosts\n                    <scp>HO<\/scp>\n                    \u20101, suppresses\n                    <scp>NF\u2010\u03baB<\/scp>\n                    , and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7810-8925","authenticated-orcid":false,"given":"Simona","family":"Cavalu","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Pharmacy University of Oradea  Oradea Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Sharaf","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Delta University for Science and Technology  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-7851","authenticated-orcid":false,"given":"Sameh","family":"Saber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Delta University for Science and Technology  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud E.","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Delta University for Science and Technology  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8630-2872","authenticated-orcid":false,"given":"Amir Mohamed","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Delta University for Science and Technology  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A. 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