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      An Appraisal of Antidotes’ Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements

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          Abstract

          Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette’s cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes’ effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist in vitro and in vivo with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote’s short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities’ approval.

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          Most cited references147

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          A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.

          Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non-protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors.
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            Suicide by intentional ingestion of pesticides: a continuing tragedy in developing countries.

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              2015 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 33rd Annual Report.

              This is the 33rd Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2015, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 9.52 [7.40, 13.6] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                26 March 2020
                April 2020
                : 25
                : 7
                : 1516
                Affiliations
                [1 ]Department of Biotechnology and Food Technology, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa
                [2 ]Department of Botany, Obafemi Awolowo University, Ile-Ife 220005, Nigeria
                [3 ]Department of Botany and Plant Biotechnology, University of Johannesburg, P.O. Box 524, Auckland Park APK 2006, South Africa
                Author notes
                [* ]Correspondence: sabius@ 123456dut.ac.za
                Author information
                https://orcid.org/0000-0003-4979-8968
                https://orcid.org/0000-0003-3820-2559
                https://orcid.org/0000-0001-7209-9220
                Article
                molecules-25-01516
                10.3390/molecules25071516
                7181008
                32225103
                41f9a2c4-934a-4288-b9c5-23296f6c4064
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 December 2019
                : 12 February 2020
                Categories
                Review

                antidotes,phyto-antidotes,poisons,secondary metabolites,snakebites,snake envenomation

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