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Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats
Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The curren...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Associação Brasileira de Divulgação Científica
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609604/ https://www.ncbi.nlm.nih.gov/pubmed/28953991 http://dx.doi.org/10.1590/1414-431X20176665 |
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author | Murad, H.A. Gazzaz, Z.J. Ali, S.S. Ibraheem, M.S. |
author_facet | Murad, H.A. Gazzaz, Z.J. Ali, S.S. Ibraheem, M.S. |
author_sort | Murad, H.A. |
collection | PubMed |
description | Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg(−1)·day(−1)) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg(−1)·day(−1)) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower “off-rate” from angiotensin-II receptors. Clinical trials are recommended. |
format | Online Article Text |
id | pubmed-5609604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Associação Brasileira de Divulgação Científica |
record_format | MEDLINE/PubMed |
spelling | pubmed-56096042017-09-29 Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats Murad, H.A. Gazzaz, Z.J. Ali, S.S. Ibraheem, M.S. Braz J Med Biol Res Research Articles Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg(−1)·day(−1)) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg(−1)·day(−1)) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower “off-rate” from angiotensin-II receptors. Clinical trials are recommended. Associação Brasileira de Divulgação Científica 2017-09-21 /pmc/articles/PMC5609604/ /pubmed/28953991 http://dx.doi.org/10.1590/1414-431X20176665 Text en http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Murad, H.A. Gazzaz, Z.J. Ali, S.S. Ibraheem, M.S. Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title | Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title_full | Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title_fullStr | Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title_full_unstemmed | Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title_short | Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
title_sort | candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609604/ https://www.ncbi.nlm.nih.gov/pubmed/28953991 http://dx.doi.org/10.1590/1414-431X20176665 |
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