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      Ameliorative effect of water spinach, Ipomea aquatica (Convolvulaceae), against experimentally induced arsenic toxicity

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          Abstract

          Background

          Ipomea aquatica (Convolvulaceae) is traditionally used against Arsenic (As) poisoning in folk medicines in India. The present study was designed to explore the therapeutic role of aqueous extract of I. aquatica (AEIA) against As-intoxication.

          Methods

          AEIA was chemically standardized by spectroscopic and chromatographic analysis. The cytoprotective role of AEIA was measured on isolated murine hepatocytes. The effect on redox status were measured after incubating the hepatocytes with NaAsO 2 (10 μM) + AEIA (400 μg/ml). The protective effect of AEIA (400 μg/ml) in expressions of apoptotic proteins were estimated in vitro. The protective role of AEIA was measured by in vivo assay in mice. Haematological, biochemical, As bioaccumulation and histological parameters were evaluated to ensure the protective role of AEIA (100 mg/kg) against NaAsO 2 (10 mg/kg) intoxication.

          Results

          Phytochemical analysis revealed presence of substantial quantities of phenolics, flavonoids, saponins and ascorbic acid in AEIA. Incubation of murine hepatocytes with AEIA (0–400 μg/ml) + NaAsO 2 (10 μM) exerted a concentration dependent cytoprotective effect. Incubation of murine hepatocytes with NaAsO 2 (10 μM, ~ IC 50) induced apoptosis via augmenting oxidative stress. NaAsO 2 treated hepatocytes exhibited significantly (p < 0.01) enhanced levels of ROS production, lipid peroxidation and protein carbonylation with concomitant depletion of antioxidant enzymes (p < 0.05-0.01) and GSH (p < 0.01) levels. However, AEIA (400 μg/ml) + NaAsO 2 (10 μM) could significantly (p < 0.05-0.01) reinstate the aforementioned parameters to near-normal status. Besides, AEIA (400 μg/ml) could significantly counteract (p <0.05-0.01) ROS mediated alteration in the expressions of apoptotic proteins viz. Bcl-2, BAD, Cyt C, Apaf 1, caspases, Fas and Bid. In in vivo bioassay, NaAsO 2 (10 mg/kg) treatment in mice caused significantly (p < 0.05-0.01) elevated As bioaccumulation, ATP levels, DNA fragmentations and oxidative stress in the liver, kidney, heart, brain and testes along with alteration in cytoarchitecture of these organs. In addition, the serum biochemical and haematological parameters were significantly (p < 0.05-0.01) altered in the NaAsO 2-treated animals. However, concurrent administration of AEIA (100 mg/ml) could significantly reinstate the NaAsO 2-induced pathogenesis.

          Conclusion

          Presence of substantial quantities of dietary antioxidants within AEIA would be responsible for overall protective effect.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12967-015-0430-3) contains supplementary material, which is available to authorized users.

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          Most cited references43

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          Phenolic content and antioxidant activity of olive extracts

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            The effects of bioactive compounds from plant foods on mitochondrial function: a focus on apoptotic mechanisms.

            Mitochondria are essential organelles for cellular integrity and functionality maintenance and their imparement is implicated in the development of a wide range of diseases, including metabolic, cardiovascular, degenerative and hyperproliferative pathologies. The identification of different compounds able to interact with mitochondria for therapeutic purposes is currently becoming of primary importance. Indeed, it is well known that foods, particularly those of vegetable origin, present several constituents with beneficial effects on health. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds from plant foods affect mitochondria functionality in healthy and pathological in vitro and in vivo models, paying particular attention to the pathways involved in mitochondrial biogenesis and apoptosis.
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              Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes.

              The Apaf-1 apoptosome is a multi-subunit caspase-activating scaffold that is assembled in response to diverse forms of cellular stress that culminate in apoptosis. To date, most studies on apoptosome composition and function have used apoptosomes reassembled from recombinant or purified proteins. Thus, the precise composition of native apoptosomes remains unresolved. Here, we have used a one-step immunopurification approach to isolate catalytically active Apaf-1/caspase-9 apoptosomes, and have identified the major constituents of these complexes using mass spectrometry methods. Using this approach, we have also assessed the ability of putative apoptosome regulatory proteins, such as Smac/DIABLO and PHAPI, to regulate the activity of native apoptosomes. We show that Apaf-1, caspase-9, caspase-3 and XIAP are the major constituents of native apoptosomes and that cytochrome c is not stably associated with the active complex. We also demonstrate that the IAP-neutralizing protein Smac/DIABLO and the tumor-suppressor protein PHAPI can enhance the catalytic activity of apoptosome complexes in distinct ways. Surprisingly, PHAPI also enhanced the activity of purified caspase-3, suggesting that it may act as a co-factor for this protease.
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                Author and article information

                Contributors
                tarunkduaju@gmail.com
                s.dewanjee@yahoo.com
                moumita_gangopadhyay@yahoo.co.uk
                ritukhanra@yahoo.co.in
                ahirzia@gmail.com
                defeo@unisa.it
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                5 March 2015
                5 March 2015
                2015
                : 13
                : 81
                Affiliations
                [ ]Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032 India
                [ ]Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, 700064 India
                [ ]The Patent Office, Karachi, 74470 Pakistan
                [ ]Department of Pharmacy, University of Salerno, Fisciano, Salerno, 84084 Italy
                Article
                430
                10.1186/s12967-015-0430-3
                4359489
                25890105
                20a4a250-750b-4038-94ba-5369d5b7a23c
                © Dua et al.; licensee BioMed Central. 2015

                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 credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 January 2015
                : 6 February 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Medicine
                apoptosis,as toxicity,ipomea aquatica,naaso2,oxidative stress
                Medicine
                apoptosis, as toxicity, ipomea aquatica, naaso2, oxidative stress

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