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Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis

(1) Background: Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the dam...

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Autores principales: Iqbal, Maryam, Shams, Sulaiman, Rafiq, Huma, Khan, Momin, Khan, Shahid, Sadique Khattak, Umer, Afridi, Sahib Gul, Bibi, Fehmida, Abdulkareem, Angham Abdulrhman, Naseer, Muhammad Imran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965641/
https://www.ncbi.nlm.nih.gov/pubmed/37259449
http://dx.doi.org/10.3390/ph16020306
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author Iqbal, Maryam
Shams, Sulaiman
Rafiq, Huma
Khan, Momin
Khan, Shahid
Sadique Khattak, Umer
Afridi, Sahib Gul
Bibi, Fehmida
Abdulkareem, Angham Abdulrhman
Naseer, Muhammad Imran
author_facet Iqbal, Maryam
Shams, Sulaiman
Rafiq, Huma
Khan, Momin
Khan, Shahid
Sadique Khattak, Umer
Afridi, Sahib Gul
Bibi, Fehmida
Abdulkareem, Angham Abdulrhman
Naseer, Muhammad Imran
author_sort Iqbal, Maryam
collection PubMed
description (1) Background: Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the damage site, thus affecting the healing process. The present study aimed to enhance the therapeutic potential of MSCs using combined therapy, along with the novel synthetic compounds of benzimidazol derivatives. (2) Methods: Eighteen compound series (benzimidazol derivatives) were screened against liver fibrosis using an in vitro CCl(4)-induced injury model on cultured hepatocytes. IC50 values were calculated on the bases of LDH assay and cell viability assay. (3) Results: Among the eighteen compounds, compounds (10), (14) and (18) were selected on the basis of IC50 value, and compound (10) was the most potent and had the lowest IC50 value in the LDH assay (8.399 [Formula: see text] 0.23 uM) and cell viability assay (4.73 [Formula: see text] 0.37 uM). Next, these compounds were combined with MSCs using an in vitro hepatocytes injury culture and in vivo rat fibrotic model. The effect of the MSCs + compounds treatment on injured hepatocytes was evaluated using LDH assay, cell viability assay, GSH assay and real-time PCR analysis and immuno-staining for caspase-3. Significant reductions in LDH level, caspase-3 and apoptotic marker genes were noted in MSCs + compounds-treated injured hepatocytes. In vivo data also showed the increased homing of the MSCs, along with compounds after transplantation. Real-time PCR analysis and TUNEL assay results also support our study. (4) Conclusions: It was concluded that compounds (10), (14) and (18) can be used in combination with MSCs to reduce liver fibrosis.
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spelling pubmed-99656412023-02-26 Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis Iqbal, Maryam Shams, Sulaiman Rafiq, Huma Khan, Momin Khan, Shahid Sadique Khattak, Umer Afridi, Sahib Gul Bibi, Fehmida Abdulkareem, Angham Abdulrhman Naseer, Muhammad Imran Pharmaceuticals (Basel) Article (1) Background: Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the damage site, thus affecting the healing process. The present study aimed to enhance the therapeutic potential of MSCs using combined therapy, along with the novel synthetic compounds of benzimidazol derivatives. (2) Methods: Eighteen compound series (benzimidazol derivatives) were screened against liver fibrosis using an in vitro CCl(4)-induced injury model on cultured hepatocytes. IC50 values were calculated on the bases of LDH assay and cell viability assay. (3) Results: Among the eighteen compounds, compounds (10), (14) and (18) were selected on the basis of IC50 value, and compound (10) was the most potent and had the lowest IC50 value in the LDH assay (8.399 [Formula: see text] 0.23 uM) and cell viability assay (4.73 [Formula: see text] 0.37 uM). Next, these compounds were combined with MSCs using an in vitro hepatocytes injury culture and in vivo rat fibrotic model. The effect of the MSCs + compounds treatment on injured hepatocytes was evaluated using LDH assay, cell viability assay, GSH assay and real-time PCR analysis and immuno-staining for caspase-3. Significant reductions in LDH level, caspase-3 and apoptotic marker genes were noted in MSCs + compounds-treated injured hepatocytes. In vivo data also showed the increased homing of the MSCs, along with compounds after transplantation. Real-time PCR analysis and TUNEL assay results also support our study. (4) Conclusions: It was concluded that compounds (10), (14) and (18) can be used in combination with MSCs to reduce liver fibrosis. MDPI 2023-02-15 /pmc/articles/PMC9965641/ /pubmed/37259449 http://dx.doi.org/10.3390/ph16020306 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iqbal, Maryam
Shams, Sulaiman
Rafiq, Huma
Khan, Momin
Khan, Shahid
Sadique Khattak, Umer
Afridi, Sahib Gul
Bibi, Fehmida
Abdulkareem, Angham Abdulrhman
Naseer, Muhammad Imran
Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title_full Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title_fullStr Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title_full_unstemmed Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title_short Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis
title_sort combinatorial therapeutic potential of stem cells and benzimidazol derivatives for the reduction of liver fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965641/
https://www.ncbi.nlm.nih.gov/pubmed/37259449
http://dx.doi.org/10.3390/ph16020306
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