title: Attrition of Hepatic Damage Inflicted by Angiotensin II with α-Tocopherol and β-Carotene in Experimental Apolipoprotein E Knock-out Mice.
abstract: Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of α-tocopherol and β-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 α-tocopherol and β-carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe(-/-)mice by infusion of Angiotensin II followed by oral administration with α-tocopherol and β-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, α-tocopherol and β-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 β-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that α-tocopherol and β-carotene treatment has salubrious role in repairing hepatic pathology.
authors.affiliation: Center for Cellular and Molecular Biology (CCMB), Uppal Road, 500007, Hyderabad, India.|Department of Orthopedic Surgery, Tissue Engineering Group (TEG), National Orthopedics Center for Excellence in Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Gopal
authors.affiliation: Center for Cellular and Molecular Biology (CCMB), Uppal Road, 500007, Hyderabad, India.
authors.forename: Munusamy
authors.initials: M
authors.lastname: Gowtham
authors.affiliation: Center for Cellular and Molecular Biology (CCMB), Uppal Road, 500007, Hyderabad, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Sachin
authors.affiliation: Department of Bio-Medical Science, Faculty of Medicine, University of Malaya, 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Mani
authors.initials: M
authors.lastname: Ravishankar Ram
authors.affiliation: Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.affiliation: Department of Orthopedic Surgery, Tissue Engineering Group (TEG), National Orthopedics Center for Excellence in Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D017382:Reactive Oxygen Species; D019207:beta Carotene; D000804:Angiotensin II; D024502:alpha-Tocopherol