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      Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

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          Abstract

          Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mortality is mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, and acute kidney injury, morbidity is caused by toxins that directly or indirectly destroy cells and degrade the extracellular matrix. These are referred to as ‘tissue-damaging toxins’ and have previously been classified in various ways, most of which are based on the tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, is primarily phenomenological and not mechanistic. In this review, we propose an alternative way of classifying cytotoxins based on their mechanistic effects rather than using a description that is organ- or tissue-based. The mechanisms of toxin-induced tissue damage and their clinical implications are discussed. This review contributes to our understanding of fundamental biological processes associated with snakebite envenoming, which may pave the way for a knowledge-based search for novel therapeutic options.

          Abstract

          The snake venom toxins responsible for tissue damage, their mechanisms of action and pathological effects are reviewed, together with the search of novel therapeutic alternatives to abrogate their effects

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          Most cited references206

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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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            The extracellular matrix at a glance.

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              Snakebite envenoming

              Snakebite envenoming is a neglected tropical disease that kills >100,000 people and maims >400,000 people every year. Impoverished populations living in the rural tropics are particularly vulnerable; snakebite envenoming perpetuates the cycle of poverty. Snake venoms are complex mixtures of proteins that exert a wide range of toxic actions. The high variability in snake venom composition is responsible for the various clinical manifestations in envenomings, ranging from local tissue damage to potentially life-threatening systemic effects. Intravenous administration of antivenom is the only specific treatment to counteract envenoming. Analgesics, ventilator support, fluid therapy, haemodialysis and antibiotic therapy are also used. Novel therapeutic alternatives based on recombinant antibody technologies and new toxin inhibitors are being explored. Confronting snakebite envenoming at a global level demands the implementation of an integrated intervention strategy involving the WHO, the research community, antivenom manufacturers, regulatory agencies, national and regional health authorities, professional health organizations, international funding agencies, advocacy groups and civil society institutions.
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                Author and article information

                Contributors
                jose.gutierrez@ucr.ac.cr
                j.kool@vu.nl
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                22 March 2024
                22 March 2024
                2024
                : 7
                : 358
                Affiliations
                [1 ]Naturalis Biodiversity Center, ( https://ror.org/0566bfb96) 2333 CR Leiden, The Netherlands
                [2 ]AIMMS, Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, ( https://ror.org/008xxew50) De Boelelaan 1085, 1081HV Amsterdam, The Netherlands
                [3 ]Centre for Analytical Sciences Amsterdam (CASA), 1098 XH Amsterdam, The Netherlands
                [4 ]Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, ( https://ror.org/03svjbs84) Pembroke Place, Liverpool, L3 5QA Liverpool, United Kingdom
                [5 ]Institute of Biology Leiden, Leiden University, ( https://ror.org/027bh9e22) Sylviusweg 72, 2333 BE Leiden, The Netherlands
                [6 ]Institute for Molecular Bioscience, The University of Queensland, St Lucia, ( https://ror.org/00rqy9422) Brisbane, Queensland Australia
                [7 ]Centre for Innovations in Peptide and Protein Science, The University of Queensland, St Lucia, ( https://ror.org/00rqy9422) Brisbane, Queensland Australia
                [8 ]Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, ( https://ror.org/02yzgww51) San José, 11501 Costa Rica
                [9 ]Present Address: Howard Hughes Medical Institute and Department of Biology, University of Maryland, ( https://ror.org/006w34k90) College Park, MD 20742 USA
                Author information
                http://orcid.org/0000-0002-5187-7342
                http://orcid.org/0000-0002-8035-4719
                http://orcid.org/0000-0001-8385-3081
                http://orcid.org/0000-0002-0011-5612
                Article
                6019
                10.1038/s42003-024-06019-6
                10960010
                38519650
                ad3ef8db-9f06-4b02-b061-d5f1420dab3e
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 August 2023
                : 7 March 2024
                Categories
                Review Article
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                © Springer Nature Limited 2024

                chronic inflammation,apoptosis
                chronic inflammation, apoptosis

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