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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9214041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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