Attrition of Hepatic Damage Inflicted by Angiotensin II with alpha-Tocopherol and beta-Carotene in Experimental Apolipoprotein E Knock-out Mice

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.

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Official URL: https://doi.org/10.1038/srep18300

Abstract

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.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Chronic Liver-Diseases; Oxidative Stress; Vitamin-E; Fibrosis; Cells; Steatohepatitis; Pathogenesis;Progression; Cirrhosis; System
Subjects: Q Science > Q Science (General)
T Technology > T Technology (General)
Depositing User: Mrs. Siti Mawarni Salim
Date Deposited: 28 Jul 2016 08:28
Last Modified: 10 Oct 2018 09:05
URI: http://eprints.um.edu.my/id/eprint/16159

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