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Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats
Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl(4))-induced liver injury and fibrosis. Liver...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722827/ https://www.ncbi.nlm.nih.gov/pubmed/35881285 http://dx.doi.org/10.1007/s11356-022-22051-7 |
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author | Amer, Maher A. Othman, Azza I. EL-Missiry, Mohamed A. Farag, Aya A. Amer, Maggie E. |
author_facet | Amer, Maher A. Othman, Azza I. EL-Missiry, Mohamed A. Farag, Aya A. Amer, Maggie E. |
author_sort | Amer, Maher A. |
collection | PubMed |
description | Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl(4))-induced liver injury and fibrosis. Liver fibrosis was induced by oral administration of CCl(4) three times a week for 5 and 9 weeks. PAs were daily administered in a dose of 500 mg/kg bw. Animals were divided into five groups: control groups, olive oil-treated group, Pas-treated group, CCl4-treated animals, and PAs + CCl4-treated rats. CCl4 and PAs were administered by gavage. Administration of CCl(4) caused a significant elevation in alanine aminotransferase and aspartate aminotransferase activities, the concentration of alpha-2-macroglobulin, and bilirubin concentration. In addition, the protein and apolipoprotein contents were significantly decreased in the serum of CCl4-treated rats. These results were accompanied by histopathological alterations and increased inflammation, apoptosis, and DNA damage. Treatment with PAs caused remarkable regression of fibrosis and alpha-2-macroglobulin with improvement in histological characteristics of the liver after 5 and 9 weeks of intoxication. PAs could also maintain redox balance, evidenced by the prevention of lipid peroxidation and mitigation of the decrease in antioxidants. Treatment of intoxicated rats with PAs resulted in a significant decline in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in serum. This is associated with a remarkable decrease in apoptosis of hepatic cells shown by decreased levels of Bax, caspase-3, and -9, with increased Bcl-2. The protective effect of PAs was also evident by protecting DNA integrity in the intoxicated rats. PAs suppressed hepatic fibrosis, improved liver function and structure via modulating the interdependence between oxidative stress, inflammation, apoptosis, and DNA integrity in CCl(4)-treated rats. |
format | Online Article Text |
id | pubmed-9722827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-97228272022-12-07 Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats Amer, Maher A. Othman, Azza I. EL-Missiry, Mohamed A. Farag, Aya A. Amer, Maggie E. Environ Sci Pollut Res Int Research Article Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl(4))-induced liver injury and fibrosis. Liver fibrosis was induced by oral administration of CCl(4) three times a week for 5 and 9 weeks. PAs were daily administered in a dose of 500 mg/kg bw. Animals were divided into five groups: control groups, olive oil-treated group, Pas-treated group, CCl4-treated animals, and PAs + CCl4-treated rats. CCl4 and PAs were administered by gavage. Administration of CCl(4) caused a significant elevation in alanine aminotransferase and aspartate aminotransferase activities, the concentration of alpha-2-macroglobulin, and bilirubin concentration. In addition, the protein and apolipoprotein contents were significantly decreased in the serum of CCl4-treated rats. These results were accompanied by histopathological alterations and increased inflammation, apoptosis, and DNA damage. Treatment with PAs caused remarkable regression of fibrosis and alpha-2-macroglobulin with improvement in histological characteristics of the liver after 5 and 9 weeks of intoxication. PAs could also maintain redox balance, evidenced by the prevention of lipid peroxidation and mitigation of the decrease in antioxidants. Treatment of intoxicated rats with PAs resulted in a significant decline in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in serum. This is associated with a remarkable decrease in apoptosis of hepatic cells shown by decreased levels of Bax, caspase-3, and -9, with increased Bcl-2. The protective effect of PAs was also evident by protecting DNA integrity in the intoxicated rats. PAs suppressed hepatic fibrosis, improved liver function and structure via modulating the interdependence between oxidative stress, inflammation, apoptosis, and DNA integrity in CCl(4)-treated rats. Springer Berlin Heidelberg 2022-07-26 2022 /pmc/articles/PMC9722827/ /pubmed/35881285 http://dx.doi.org/10.1007/s11356-022-22051-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Amer, Maher A. Othman, Azza I. EL-Missiry, Mohamed A. Farag, Aya A. Amer, Maggie E. Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title | Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title_full | Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title_fullStr | Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title_full_unstemmed | Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title_short | Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats |
title_sort | proanthocyanidins attenuated liver damage and suppressed fibrosis in ccl4-treated rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722827/ https://www.ncbi.nlm.nih.gov/pubmed/35881285 http://dx.doi.org/10.1007/s11356-022-22051-7 |
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