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      A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats

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          Abstract

          Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.

          Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.

          Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.

          Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.

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          Most cited references101

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          UCSF Chimera--a visualization system for exploratory research and analysis.

          The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/. Copyright 2004 Wiley Periodicals, Inc.
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            ROS function in redox signaling and oxidative stress.

            Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS also act as signaling molecules in the maintenance of physiological functions--a process termed redox biology. In this review we discuss the two faces of ROS--redox biology and oxidative stress--and their contribution to both physiological and pathological conditions. Redox biology involves a small increase in ROS levels that activates signaling pathways to initiate biological processes, while oxidative stress denotes high levels of ROS that result in damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis, given that the opposite effect is observed at low levels compared with that seen at high levels. Here, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Bioavailability of curcumin: problems and promises.

              Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                04 May 2023
                2023
                : 10
                : 1172403
                Affiliations
                [1] 1 Biochemistry Department , Faculty of Science , King Abdulaziz University , Jeddah, Saudi Arabia
                [2] 2 Department of Chemistry , Faculty of Science , Sohag University , Sohag, Egypt
                [3] 3 Ibn Sina National College for Medical Studies , Jeddah, Saudi Arabia
                [4] 4 Biochemistry Department , Faculty of Pharmacy , Beni Suef University , Beni Suef, Egypt
                [5] 5 Histology and Cell biology Department , Faculty of Medicine , Sohag University , Sohag, Egypt
                Author notes

                Edited by: Enis Kostallari, Mayo Clinic, United States

                Reviewed by: Yiling Li, The First Affiliated Hospital of China Medical University, China

                Jasim Khan, University of Alabama at Birmingham, United States

                *Correspondence: Maryam H. Al-Zahrani, mhsalzahrani@ 123456kau.edu.sa
                [ † ]

                ORCID: Maryam H. Al-Zahrani, orcid.org/0000-0002-1234-7947; Sahar M Gebril, orcid.org/0000-0002-8679-4897

                Article
                1172403
                10.3389/fmolb.2023.1172403
                10192634
                37214337
                cc51a2d0-56c8-4e2c-92c8-2e66446c61d2
                Copyright © 2023 Al-Zahrani, Balgoon, El-Sawi, Alshubaily, Jambi, Khojah, Baljoon, Alkhattabi, Baz, Alharbi, Ahmed, Abo elkhair, Ismael and Gebril.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 February 2023
                : 10 April 2023
                Categories
                Molecular Biosciences
                Original Research
                Custom metadata
                Molecular Diagnostics and Therapeutics

                t-2 toxin,hepatotoxicity,fibrosis,dna damage,apoptosis,curcumin,taurine,molecular docking

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