Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Cavalu S.; Sharaf H.; Saber S.; Youssef M.E.; Abdelhamid A.M.; Mourad A.A.E.; Ibrahim S.; Allam S.; Elgharabawy R.M.; El-Ahwany E.; Amin N.A.; Shata A.; Eldegla M.; Atef M.; Aboraya M.; Mohamed M.; Anz N.; Elmotelb D.A.; Gabr F.; Elzablawy D.; Hamada M.; Yehia A.; Osama D.; Mohammed O.A.

Journal: FASEB Journal

Publisher: John Wiley and Sons Inc

Publication Date: 10 August 2022

Volume / Issue: Volume 36 / Issue 9

Article No.: e22496

ISSN: 8926638

DOI: 10.1096/fj.202200749R

Scopus: View on Scopus

PubMed: 35947115

Document Type: Article

Access: All Open Access; Hybrid Gold Open Access

Authors and Affiliations

Cavalu S., Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania; Sharaf H., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Youssef M.E., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Abdelhamid A.M., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Mourad A.A.E., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, Egypt; Ibrahim S., Department of Pharmacy Practice, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; Allam S., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt; Elgharabawy R.M., Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; El-Ahwany E., Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt; Amin N.A., Department of Haematology, Theodor Bilharz Research Institute, Giza, Egypt; Shata A., Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt, Department of Clinical Pharmacy, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Eldegla M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Atef M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Aboraya M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Mohamed M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Anz N., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Elmotelb D.A., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Gabr F., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Elzablawy D., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Hamada M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Yehia A., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Osama D., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Mohammed O.A., Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt, Department of Clinical Pharmacology, Faculty of medicine, Bisha University, Bisha, Saudi Arabia

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. 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-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory 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 mg/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-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 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-inflammatory, antioxidant, and antiapoptotic properties. © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Keywords

ambroxol hydrochloride; HO-1; NF-κB; Nrf2; oxidative stress; ulcerative colitis; Ambroxol; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Colitis, Ulcerative; Colon; Expectorants; Humans; NF-E2-Related Factor 2; NF-kappa B; Rats; acetic acid; catalase; heme oxygenase 1; immunoglobulin enhancer binding protein; interleukin 10; interleukin 6; myeloperoxidase; protein Bax; protein bcl 2; synaptotagmin I; transcription factor Nrf2; tumor necrosis factor; antiinflammatory agent; antioxidant; expectorant agent; animal experiment; animal model; animal tissue; antiinflammatory activity; antioxidant activity; Article; colon weight; controlled study; disease activity; drug megadose; enzyme activity; inflammation; male; morning dosage; NF kB signaling; nonhuman; rat; signal transduction; upregulation; animal; human

Citation Information

Scopus Citations: 44

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