Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice
Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of alpha-tocopherol and beta-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the rol...
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Nature Research
2015
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| author | Gopal, K. Gowtham, M. Sachin, S. Ram, M.R. Shankar, E.M. Kamarul, Tunku |
| author_facet | Gopal, K. Gowtham, M. Sachin, S. Ram, M.R. Shankar, E.M. Kamarul, Tunku |
| author_sort | Gopal, K. |
| collection | UM |
| description | Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of alpha-tocopherol and beta-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the role of Angiotensin II on hepatic damage and if alpha-tocopherol and beta-carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe(-/-) mice by infusion of Angiotensin II followed by oral administration with alpha-tocopherol and beta-carotene-enriched diet for 60 days. Investigations showed fibrosis, kupffer cell hyperplasia, hepatocyte degeneration and hepatic cell apoptosis; sinusoidal dilatation along with haemorrhages; evidence of fluid accumulation; increased ROS level and increased AST and ALT activities. In addition, tPA and uPA were down-regulated due to 42-fold up-regulation of PAI-1. MMP-2, MMP-9, MMP-12, and M-CSF were down-regulated in Angiotensin II-treated animals. Notably, alpha-tocopherol and beta-carotene treatment controlled ROS, fibrosis, hepatocyte degeneration, kupffer cell hyperplasia, hepatocyte apoptosis, sinusoidal dilatation and fluid accumulation in the liver sinusoids, and liver enzyme levels. In addition, PAI-1, tPA and uPA expressions were markedly controlled by beta-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that alpha-tocopherol and beta-carotene treatment has salubrious role in repairing hepatic pathology. |
| first_indexed | 2024-03-06T05:40:23Z |
| format | Article |
| id | um.eprints-16159 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:40:23Z |
| publishDate | 2015 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | um.eprints-161592018-10-10T09:05:58Z http://eprints.um.edu.my/16159/ Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice Gopal, K. Gowtham, M. Sachin, S. Ram, M.R. Shankar, E.M. Kamarul, Tunku Q Science (General) T Technology (General) Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of alpha-tocopherol and beta-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the role of Angiotensin II on hepatic damage and if alpha-tocopherol and beta-carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe(-/-) mice by infusion of Angiotensin II followed by oral administration with alpha-tocopherol and beta-carotene-enriched diet for 60 days. Investigations showed fibrosis, kupffer cell hyperplasia, hepatocyte degeneration and hepatic cell apoptosis; sinusoidal dilatation along with haemorrhages; evidence of fluid accumulation; increased ROS level and increased AST and ALT activities. In addition, tPA and uPA were down-regulated due to 42-fold up-regulation of PAI-1. MMP-2, MMP-9, MMP-12, and M-CSF were down-regulated in Angiotensin II-treated animals. Notably, alpha-tocopherol and beta-carotene treatment controlled ROS, fibrosis, hepatocyte degeneration, kupffer cell hyperplasia, hepatocyte apoptosis, sinusoidal dilatation and fluid accumulation in the liver sinusoids, and liver enzyme levels. In addition, PAI-1, tPA and uPA expressions were markedly controlled by beta-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that alpha-tocopherol and beta-carotene treatment has salubrious role in repairing hepatic pathology. Nature Research 2015 Article PeerReviewed Gopal, K. and Gowtham, M. and Sachin, S. and Ram, M.R. and Shankar, E.M. and Kamarul, Tunku (2015) Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice. Scientific Reports, 5. p. 18300. ISSN 2045-2322, DOI https://doi.org/10.1038/srep18300 <https://doi.org/10.1038/srep18300>. https://doi.org/10.1038/srep18300 doi:10.1038/srep18300 |
| spellingShingle | Q Science (General) T Technology (General) Gopal, K. Gowtham, M. Sachin, S. Ram, M.R. Shankar, E.M. Kamarul, Tunku Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title | Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title_full | Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title_fullStr | Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title_full_unstemmed | Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title_short | Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice |
| title_sort | attrition of hepatic damage inflicted by angiotensin ii with alpha tocopherol and beta carotene in experimental apolipoprotein e knock out mice |
| topic | Q Science (General) T Technology (General) |
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