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      Sicyos angulatus ameliorates acute liver injury by inhibiting oxidative stress via upregulation of anti-oxidant enzymes

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          ABSTRACT

          Objective: We aimed to investigate the effect of Sicyos angulatus (SA) ethanolic extracts as antioxidants and potential treatments for liver disease.

          Methods: To establish a mouse model of liver injury, C57BL/6 male mice were injected via the caudal vein with a single dose of concanavalin A (Con A, 15 mg kg −1). SA extracts were administered once by oral gavage 30 min before Con A injection.

          Results: In vitro studies showed that SA decreased tert-butyl hydroperoxide ( t-BHP)-induced reactive oxygen species (ROS) production. SA administration reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as hepatic ROS levels, in a dose-dependent manner. Moreover, SA increased the activities of the hepatic antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. Furthermore, SA treatment reduced pro-apoptotic protein levels. Con A-mediated cytosolic release of Smac/DIABLO and apoptosis-inducing factor (AIF), which are markers of necrosis, were dramatically decreased in HepG2 cells treated with SA.

          Conclusion: SA ameliorated liver injury and might be a good strategy for the treatment of liver injury.

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          Most cited references19

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          Hepatic T cells and liver tolerance.

          The T-cell biology of the liver is unlike that of any other organ. The local lymphocyte population is enriched in natural killer (NK) and NKT cells, which might have crucial roles in the recruitment of circulating T cells. A large macrophage population and the efficient trafficking of dendritic cells from sinusoidal blood to lymph promote antigen trapping and T-cell priming, but the local presentation of antigen causes T-cell inactivation, tolerance and apoptosis. These local mechanisms might result from the need to maintain immunological silence to harmless antigenic material in food. The overall bias of intrahepatic T-cell responses towards tolerance might account for the survival of liver allografts and for the persistence of some liver pathogens.
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            Concanavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor necrosis factor.

            Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of concanavalin A-induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On concanavalin A challenge, the cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-gamma were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-alpha antiserum protected them from concanavalin A-induced liver injury. Nude mice failed to release TNF-alpha or interleukin-2 after concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in concanavalin A-stimulated TNF-alpha release in vivo. After intravenous administration of fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence was found within the liver. In vitro, concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-alpha. These findings may explain the hepatotropic effect of concanavalin A. In conclusion, T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokine-mediated disorders and possibly to autoreactive hepatic processes.
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              Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system.

              Acute liver failure induced by acetaminophen (APAP) overdose is the main cause of drug-induced liver injury (DILI). Caffeic acid (CA) is a phenolic compound from many natural products. This study aims to investigate the protective mechanism of CA in APAP-induced liver injury. The results of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, liver glutathione (GSH) and reactive oxygen species (ROS) levels demonstrated the protection of CA against APAP-induced liver injury. Liver histological observation provided further evidences of CA-induced protection. CA was found to reverse the APAP-induced decreased cell viability in human normal liver L-02 cells and HepG2 cells. CA also reduced the increased cellular ROS level induced by APAP in hepatocytes. The results of luciferase assay and Western-blot analysis showed that CA increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of APAP. Nrf2 siRNA reduced the protection of CA against APAP-induced hepatotoxicity. CA also reversed the APAP-induced decreased mRNA and protein expression of heme oxygenase 1 (HO-1) and
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                Author and article information

                Journal
                Redox Rep
                Redox Rep
                YRER
                yrer20
                Redox Report : Communications in Free Radical Research
                Taylor & Francis
                1351-0002
                1743-2928
                2018
                14 November 2018
                : 23
                : 1
                : 206-212
                Affiliations
                [a ]Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Republic of Korea
                [b ]University of Science and Technology , Daejeon, Republic of Korea
                [c ]Department of Food and Nutrition, Chungnam National University , Daejeon, Republic of Korea
                [d ]Research Institute of Pharmaceutical Sciences, College of Pharmacy, Korea Bioactive Natural Material Bank, Seoul National University , Seoul, Republic of Korea
                Author notes
                [CONTACT ] Jung Hwan Hwang coccs99@ 123456kribb.re.kr Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), University of Science and Technology , 125 Gwahak-ro, Yuseong-gu, Daejeon34141, Republic of Korea
                Chul-Ho Lee chullee@ 123456kribb.re.kr Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), University of Science and Technology , 125 Gwahak-ro, Yuseong-gu, Daejeon34141, Republic of Korea
                Author information
                http://orcid.org/0000-0002-6996-5746
                Article
                1546986
                10.1080/13510002.2018.1546986
                6748690
                30426855
                a7d95bde-e18d-40e6-9073-403524d428d9
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 April 2018
                : 01 November 2018
                Page count
                Figures: 5, Tables: 0, Equations: 3, References: 31, Pages: 7
                Funding
                Funded by: National Research Foundation of Korea (NRF) 10.13039/501100003725
                Funded by: Korean government (MSIP)
                Award ID: 2016R1A2A1A05004858
                Funded by: KRIBB Research Initiative Program of the Republic of Korea
                This work was supported by a grant from the National Research Foundation of Korea (NRF) and the Korean government (MSIP) (2016R1A2A1A05004858), and the KRIBB Research Initiative Program of the Republic of Korea (KGS 1001814).
                Categories
                Research Article

                Inorganic & Bioinorganic chemistry
                antioxidants,apoptosis,reactive oxygen species,liver,oxidative stress,injury,enzyme,extracts

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