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Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options...

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Autores principales: Abdelhamid, Amir Mohamed, Youssef, Mahmoud E., Cavalu, Simona, Mostafa-Hedeab, Gomaa, Youssef, Amal, Elazab, Sara T., Ibrahim, Samar, Allam, Shady, Elgharabawy, Rehab Mohamed, El-Ahwany, Eman, Amin, Noha A., Shata, Ahmed, Mohammed, Osama A., Ibrahim Abdeldaiem, Mahmoud Said, Alhowail, Ahmed, El-Saber Batiha, Gaber, El-Mahmoudy, Engy A., Attia, Maram, Allam, Alaa, Zaater, Mona Y., Osman, Mona M., Nader, Manar, Taha, Aya, Makarem, Nada Abul, Saber, Sameh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214041/
https://www.ncbi.nlm.nih.gov/pubmed/35754464
http://dx.doi.org/10.3389/fphar.2022.887233
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author Abdelhamid, Amir Mohamed
Youssef, Mahmoud E.
Cavalu, Simona
Mostafa-Hedeab, Gomaa
Youssef, Amal
Elazab, Sara T.
Ibrahim, Samar
Allam, Shady
Elgharabawy, Rehab Mohamed
El-Ahwany, Eman
Amin, Noha A.
Shata, Ahmed
Mohammed, Osama A.
Ibrahim Abdeldaiem, Mahmoud Said
Alhowail, Ahmed
El-Saber Batiha, Gaber
El-Mahmoudy, Engy A.
Attia, Maram
Allam, Alaa
Zaater, Mona Y.
Osman, Mona M.
Nader, Manar
Taha, Aya
Makarem, Nada Abul
Saber, Sameh
author_facet Abdelhamid, Amir Mohamed
Youssef, Mahmoud E.
Cavalu, Simona
Mostafa-Hedeab, Gomaa
Youssef, Amal
Elazab, Sara T.
Ibrahim, Samar
Allam, Shady
Elgharabawy, Rehab Mohamed
El-Ahwany, Eman
Amin, Noha A.
Shata, Ahmed
Mohammed, Osama A.
Ibrahim Abdeldaiem, Mahmoud Said
Alhowail, Ahmed
El-Saber Batiha, Gaber
El-Mahmoudy, Engy A.
Attia, Maram
Allam, Alaa
Zaater, Mona Y.
Osman, Mona M.
Nader, Manar
Taha, Aya
Makarem, Nada Abul
Saber, Sameh
author_sort Abdelhamid, Amir Mohamed
collection PubMed
description Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.
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spelling pubmed-92140412022-06-23 Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis Abdelhamid, Amir Mohamed Youssef, Mahmoud E. Cavalu, Simona Mostafa-Hedeab, Gomaa Youssef, Amal Elazab, Sara T. Ibrahim, Samar Allam, Shady Elgharabawy, Rehab Mohamed El-Ahwany, Eman Amin, Noha A. Shata, Ahmed Mohammed, Osama A. Ibrahim Abdeldaiem, Mahmoud Said Alhowail, Ahmed El-Saber Batiha, Gaber El-Mahmoudy, Engy A. Attia, Maram Allam, Alaa Zaater, Mona Y. Osman, Mona M. Nader, Manar Taha, Aya Makarem, Nada Abul Saber, Sameh Front Pharmacol Pharmacology Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC. Frontiers Media S.A. 2022-06-08 /pmc/articles/PMC9214041/ /pubmed/35754464 http://dx.doi.org/10.3389/fphar.2022.887233 Text en Copyright © 2022 Abdelhamid, Youssef, Cavalu, Mostafa-Hedeab, Youssef, Elazab, Ibrahim, Allam, Elgharabawy, El-Ahwany, Amin, Shata, Mohammed, Ibrahim Abdeldaiem, Alhowail, El-Saber Batiha, El-Mahmoudy, Attia, Allam, Zaater, Osman, Nader, Taha, Makarem and Saber. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Abdelhamid, Amir Mohamed
Youssef, Mahmoud E.
Cavalu, Simona
Mostafa-Hedeab, Gomaa
Youssef, Amal
Elazab, Sara T.
Ibrahim, Samar
Allam, Shady
Elgharabawy, Rehab Mohamed
El-Ahwany, Eman
Amin, Noha A.
Shata, Ahmed
Mohammed, Osama A.
Ibrahim Abdeldaiem, Mahmoud Said
Alhowail, Ahmed
El-Saber Batiha, Gaber
El-Mahmoudy, Engy A.
Attia, Maram
Allam, Alaa
Zaater, Mona Y.
Osman, Mona M.
Nader, Manar
Taha, Aya
Makarem, Nada Abul
Saber, Sameh
Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title_full Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title_fullStr Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title_full_unstemmed Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title_short Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis
title_sort carbocisteine as a modulator of nrf2/ho-1 and nfκb interplay in rats: new inspiration for the revival of an old drug for treating ulcerative colitis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214041/
https://www.ncbi.nlm.nih.gov/pubmed/35754464
http://dx.doi.org/10.3389/fphar.2022.887233
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