{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:45:12Z","timestamp":1789854312594,"version":"4.0.1"},"reference-count":131,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Skeletal muscle regeneration after myonecrosis involves the activation, proliferation and fusion of myogenic cells, and a coordinated inflammatory response encompassing phagocytosis of necrotic cell debris, and the concerted synthesis of cytokines and growth factors. Myonecrosis often occurs in snakebite envenomings. In the case of venoms that cause myotoxicity without affecting the vasculature, such as those of many elapid snakes, regeneration proceeds successfully. In contrast, in envenomings by most viperid snakes, which affect the vasculature and extracellular matrix in addition to muscle fibers, regeneration is largely impaired and, therefore, the muscle mass is reduced and replaced by fibro-adipose tissue. This review discusses possible causes for such poor regenerative outcome including: (a) damage to muscle microvasculature, which causes tissue hypoxia and affects the inflammatory response and the timely removal of necrotic tissue; (b) damage to intramuscular nerves, which results in atrophy of regenerating fibers; (c) degradation of muscle cell basement membrane, compromising the spatial niche for proliferating myoblasts; (d) widespread degradation of the extracellular matrix; and (e) persistence of venom components in the damaged tissue, which may affect myogenic cells at critical points in the regenerative process. Understanding the causes of poor muscle regeneration may pave the way for the development of novel therapeutic interventions aimed at fostering the regenerative process in envenomed patients.<\/jats:p>","DOI":"10.3390\/toxins10050182","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T03:20:27Z","timestamp":1525317627000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Why is Skeletal Muscle Regeneration Impaired after Myonecrosis Induced by Viperid Snake Venoms?"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3081","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Guti\u00e9rrez","sequence":"first","affiliation":[{"name":"Instituto Clodomiro Picado, Facultad de Microbiolog\u00eda, Universidad de Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Escalante","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, Facultad de Microbiolog\u00eda, Universidad de Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala City 01012, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-8452","authenticated-orcid":false,"given":"Stefano","family":"Gastaldello","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-17177, Sweden"},{"name":"Precision Medicine Research Center, Binzhou Medical University, Laishan District, Guanhai Road 346, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Saravia-Otten","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala City 01012, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rucavado","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, Facultad de Microbiolog\u00eda, Universidad de Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0140-6736(09)61754-2","article-title":"Snake bite","volume":"375","author":"Warrell","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","unstructured":"Cardoso, J.L.C., Franca, F.O.D.S., Wen, F.H., Malaque, C.M.S., and Haddad Junior, V. (2009). Animais pe\u00e7onhentos no Brasil: Biologia, clinica e terap\u00eautica dos acidentes, S\u00e3o Paulo Sarvier."},{"key":"ref_4","unstructured":"Warrell, D.A. (1995). Clinical toxicology of snakebite in Africa and the Middle East\/Arabian peninsula. Handbook of Clinical Toxicology of Animal Venoms and Poisons, CRC Press."},{"key":"ref_5","unstructured":"Lamar, W.W, and Campbell, J.A. (2004). Snakebites in Central and South America: Epidemiology, clinical features, and clinical management. The Venomous Reptiles of the Western Hemisphere, Cornell University Press."},{"key":"ref_6","unstructured":"White, J. (1995). Clinical Toxicology of snakebite in Australia and New Guinea. Handbook of Clinical Toxicology of Animal Venoms and Poisons, CRC Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0041-0101(85)90367-8","article-title":"Myonecrosis, myoglobinuria and acute renal failure induced by south american rattlesnake (Crotalus durissus terrificus) envenomation in Brazil","volume":"23","author":"Cupo","year":"1985","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.toxicon.2009.07.001","article-title":"Epidemiological, clinical and therapeutic aspects of Bothrops asper bites","volume":"54","year":"2009","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.toxicon.2009.08.006","article-title":"Tissue pathology induced by snake venoms: How to understand a complex pattern of alterations from a systems biology perspective?","volume":"55","author":"Rucavado","year":"2010","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1586\/epr.11.61","article-title":"Proteomic tools against the neglected pathology of snake bite envenoming","volume":"8","author":"Calvete","year":"2011","journal-title":"Expert Rev. Proteom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.toxicon.2003.11.005","article-title":"Skeletal muscle degeneration induced by venom phospholipases A 2: Insights into the mechanisms of local and systemic myotoxicity","volume":"42","author":"Ownby","year":"2003","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1007\/s00018-008-8113-3","article-title":"Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: Common aspects of their mechanisms of action","volume":"65","author":"Montecucco","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0041-0101(93)90376-T","article-title":"Cardiotoxin 1 from cobra (Naja naja atra) venom causes necrosis of skeletal muscle in vivo","volume":"31","author":"Ownby","year":"1993","journal-title":"Toxicon"},{"key":"ref_14","first-page":"149","article-title":"Isolation of myotoxic component from rattlesnake (Crotalus viridis viridis) venom. Electron microscopic analysis of muscle damage","volume":"85","author":"Ownby","year":"1976","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0300-9084(00)01163-9","article-title":"Snake venom metalloproteinases: Their role in the pathogenesis of local tissue damage","volume":"82","author":"Rucavado","year":"2000","journal-title":"Biochimie"},{"key":"ref_16","unstructured":"Schiafino, S., and Partridge, T. (2008). Skeletal Muscle Repair and Regeneration. Skeletal Muscle Repair and Regeneration, Springer."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1152\/physrev.00019.2003","article-title":"Cellular and molecular regulation of muscle regeneration","volume":"84","author":"Rudnicki","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"906","DOI":"10.2174\/138161210790883453","article-title":"Regeneration of Mammalian Skeletal Muscle: Basic Mechanisms and Clinical Implications","volume":"16","author":"Ciciliot","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","first-page":"779","article-title":"Muscle regeneration: Cellular and molecular events","volume":"23","author":"Karalaki","year":"2009","journal-title":"In Vivo"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bone.2015.02.028","article-title":"Molecular mechanisms of skeletal muscle development, regeneration, and osteogenic conversion","volume":"80","author":"Endo","year":"2015","journal-title":"Bone"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1152\/jappl.2001.91.2.534","article-title":"Myogenic satellite cells: Physiology to molecular biology","volume":"91","author":"Hawke","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ten Broek, R.W., Grefte, S., and Von den Hoff, J.W. (2010). Regulatory factors and cell populations involved in skeletal muscle regeneration. J. Cell. Physiol., 224.","DOI":"10.1002\/jcp.22127"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nri.2016.150","article-title":"Regulation of muscle growth and regeneration by the immune system","volume":"17","author":"Tidball","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tidball, J.G. (2008). Inflammation in Skeletal Muscle Regeneration. Skeletal Muscle Repair and Regeneration, Springer.","DOI":"10.1007\/978-1-4020-6768-6_12"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Juban, G., and Chazaud, B. (2017). Metabolic regulation of macrophages during tissue repair: Insights from skeletal muscle regeneration. FEBS Lett., 1\u201315.","DOI":"10.1002\/1873-3468.12703"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"491497","DOI":"10.1155\/2013\/491497","article-title":"Macrophage plasticity and the role of inflammation in skeletal muscle repair","volume":"2013","author":"Kharraz","year":"2013","journal-title":"Med. Inflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/art.27183","article-title":"Muscle resident macrophages control the immune cell reaction in a mouse model of notexin-induced myoinjury","volume":"62","author":"Brigitte","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.arr.2016.03.006","article-title":"Regenerative function of immune system: Modulation of muscle stem cells","volume":"27","author":"Saini","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1177\/002215540104900807","article-title":"The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(-\/-) and TNF-alpha(-\/-)\/LT-alpha(-\/-) mice","volume":"49","author":"Collins","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"C1183","DOI":"10.1152\/ajpcell.00568.2007","article-title":"Endogenous interferon-gamma is required for efficient skeletal muscle regeneration","volume":"294","author":"Cheng","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3389\/fimmu.2015.00212","article-title":"Anatomy of a Discovery: M1 and M2 Macrophages","volume":"6","author":"Mills","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Grounds, M.D. (2008). Complexity of Extracellular Matrix and Skeletal Muscle Regeneration. Skeletal Muscle Repair and Regeneration, Springer.","DOI":"10.1007\/978-1-4020-6768-6_13"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1242\/jcs.03158","article-title":"Multifunctional roles of MT1-MMP in myofiber formation and morphostatic maintenance of skeletal muscle","volume":"119","author":"Ohtake","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/mus.10529","article-title":"Matrix metalloproteinases and skeletal muscle: A brief review","volume":"29","author":"Carmeli","year":"2004","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/mus.20383","article-title":"Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation","volume":"32","author":"Lluri","year":"2005","journal-title":"Muscle Nerve"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"C529","DOI":"10.1152\/ajpcell.00051.2013","article-title":"Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration","volume":"305","author":"Lei","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2353\/ajpath.2009.080509","article-title":"Matrix Metalloproteinase-1 Promotes Muscle Cell Migration and Differentiation","volume":"174","author":"Wang","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10974-015-9414-4","article-title":"MMP-14 in skeletal muscle repair","volume":"36","author":"Snyman","year":"2015","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10555-006-7893-x","article-title":"Novel functions of TIMPs in cell signaling","volume":"25","author":"Chirco","year":"2006","journal-title":"Cancer Metastasis Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/ncb2015","article-title":"Muscle injury activates resident fibro\/adipogenic progenitors that facilitate myogenesis","volume":"12","author":"Joe","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1016\/j.yexcr.2010.05.035","article-title":"Regulation and dysregulation of fibrosis in skeletal muscle","volume":"316","author":"Serrano","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How Matrix Metalloproteinases Regulate Cell Behavior","volume":"17","author":"Sternlicht","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1083\/jcb.55.2.406","article-title":"Basal lamina: The scaffold for orderly cell replacement. Observations on regeneration of injured skeletal muscle fibers and capillaries","volume":"55","author":"Vracko","year":"1972","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Slater, C.R., and Schiaffino, S. (2008). Innervation of Regenerating Muscle. Skeletal Muscle Repair and Regeneration, Springer.","DOI":"10.1007\/978-1-4020-6768-6_14"},{"key":"ref_45","unstructured":"Fran\u00e7a, F.O.S., and M\u00e1laque, C.M. (2009). Acidente botr\u00f3pico. Animais Pe\u00e7onhentos no Brasil. Biologia, Cl\u00ednica e Terap\u00eautica dos Acidentes, Sarvier."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"White, J. (2010). Envenomation. Prevention and treatment in Australia. Handbook of Venoms and Toxins of Reptiles, CRC Press.","DOI":"10.1201\/9781420008661.sec4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.toxicon.2012.06.012","article-title":"Renal effects and injury induced by animal toxins","volume":"60","author":"Sitprija","year":"2012","journal-title":"Toxicon"},{"key":"ref_48","first-page":"323","article-title":"A histopathological study on arterial lesions caused by Habu (Trimeresurus flavoviridis) venom","volume":"37","author":"Homma","year":"1967","journal-title":"Jpn. J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.toxicon.2016.06.006","article-title":"Pathogenesis of dermonecrosis induced by venom of the spitting cobra, Naja nigricollis: An experimental study in mice","volume":"119","author":"Rivel","year":"2016","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/S0041-0101(02)00104-6","article-title":"Complications of Bothrops, Porthidium, and Bothriechis snakebites in Colombia. A clinical and epidemiological study of 39 cases attended in a university hospital","volume":"40","author":"Otero","year":"2002","journal-title":"Toxicon"},{"key":"ref_51","unstructured":"Dart, R.C., McNally, J.T., Spaite, D.W., and Gustafson, R. (1992). The sequelae of pitviper poisoning in the United States. Biology of the Pitvipers, Selva."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jayawardana, S., Gnanathasan, A., Arambepola, C., and Chang, T. (2016). Chronic Musculoskeletal Disabilities following Snake Envenoming in Sri Lanka: A Population-Based Study. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005103"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1440-1681.1978.tb00714.x","article-title":"Further observations on the pathological responses of rat skeletal muscle to toxins isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus","volume":"5","author":"Harris","year":"1978","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1476-5381.1982.tb09191.x","article-title":"Myotoxic activity of the crude venom and the principal neurotoxin, taipoxin, of the Australian taipan, Oxyuranus scutellatus","volume":"76","author":"Harris","year":"1982","journal-title":"Br. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/BF00216429","article-title":"Regeneration of mammalian skeletal muscle following the injection of the snake-venom toxin, taipoxin","volume":"232","author":"Maltin","year":"1983","journal-title":"Cell Tissue Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.toxicon.2003.11.011","article-title":"Myotoxic phospholipases A2 and the regeneration of skeletal muscles","volume":"42","author":"Harris","year":"2003","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1113\/expphysiol.2013.077289","article-title":"Properties of regenerated mouse extensor digitorum longus muscle following notexin injury","volume":"99","author":"Head","year":"2014","journal-title":"Exp. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/0022-510X(74)90041-0","article-title":"Changes in motor end-plates resulting from muscle fibre necrosis and regeneration. A light and electron microscopic study of the effects of the depolarizing fraction (cardiotoxin) of Dendroaspis jamesoni venom","volume":"21","author":"Duchen","year":"1974","journal-title":"J. Neurol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hardy, D., Besnard, A., Latil, M., Jouvion, G., Briand, D., Th\u00e9penier, C., Pascal, Q., Guguin, A., Gayraud-Morel, B., and Cavaillon, J.M. (2016). Comparative Study of Injury Models for Studying Muscle Regeneration in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147198"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Guardiola, O., Andolfi, G., Tirone, M., Iavarone, F., Brunelli, S., and Minchiotti, G. (2017). Induction of Acute Skeletal Muscle Regeneration by Cardiotoxin Injection. J. Vis. Exp.","DOI":"10.3791\/54515-v"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/0041-0101(84)90155-7","article-title":"Skeletal muscle regeneration after myonecrosis induced by crude venom and a myotoxin from the snake Bothrops asper (Fer-de-Lance)","volume":"22","author":"Ownby","year":"1984","journal-title":"Toxicon"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, R., Cabalceta, C., Saravia-Otten, P., Chaves, A., Guti\u00e9rrez, J.M., and Rucavado, A. (2011). Poor regenerative outcome after skeletal muscle necrosis induced by Bothrops asper venom: Alterations in microvasculature and nerves. PLoS ONE, 6.","DOI":"10.1371\/annotation\/9caa2be8-b5e6-4553-8575-f0b575442172"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0014-4800(91)90002-F","article-title":"Skeletal muscle degeneration and regeneration after injection of bothropstoxin-II, a phospholipase A2 isolated from the venom of the snake Bothrops jararacussu","volume":"55","author":"Cintra","year":"1991","journal-title":"Exp. Mol. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/0041-0101(89)90040-8","article-title":"Myonecrosis induced in mice by a basic myotoxin isolated from the venom of the snake Bothrops nummifer (jumping viper) from Costa Rica","volume":"27","author":"Chaves","year":"1989","journal-title":"Toxicon"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/(SICI)1097-0185(19990401)254:4<521::AID-AR7>3.0.CO;2-8","article-title":"Long-term regeneration of fast and slow murine skeletal muscles after induced injury by ACL myotoxin isolated from Agkistrodon contortrix laticinctus (broad-banded copperhead) venom","volume":"254","author":"Salvini","year":"1999","journal-title":"Anat. Rec."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.toxicon.2008.04.177","article-title":"Radicicol improves regeneration of skeletal muscle previously damaged by crotoxin in mice","volume":"52","author":"Conte","year":"2008","journal-title":"Toxicon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0014-4800(90)90055-I","article-title":"Changes in myofibrillar components after skeletal muscle necrosis induced by a myotoxin isolated from the venom of the snake Bothrops asper","volume":"52","author":"Arce","year":"1990","journal-title":"Exp. Mol. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/09629350220131980","article-title":"Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snake Bothrops asper","volume":"11","author":"Rucavado","year":"2002","journal-title":"Med. Inflamm."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rucavado, A., Nicolau, C.A., Escalante, T., Kim, J., Herrera, C., Guti\u00e9rrez, J.M., and Fox, J.W. (2016). Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs\/TLR-4 Mediated Pathway. Toxins, 8.","DOI":"10.3390\/toxins8120349"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.toxicon.2008.12.025","article-title":"Insights of local tissue damage and regeneration induced by BnSP-7, a myotoxin isolated from Bothrops (neuwiedi) pauloensis snake venom","volume":"53","author":"Oliveira","year":"2009","journal-title":"Toxicon"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxicon.2009.03.019","article-title":"Inflammation induced by Bothrops asper venom","volume":"54","author":"Teixeira","year":"2009","journal-title":"Toxicon"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Herrera, C., Mac\u00eado, J.K.A., Feoli, A., Escalante, T., Rucavado, A., Guti\u00e9rrez, J.M., and Fox, J.W. (2016). Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004599"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/mus.23489","article-title":"Homogenates of skeletal muscle injected with snake venom inhibit myogenic differentiation in cell culture","volume":"47","author":"Robledo","year":"2013","journal-title":"Muscle Nerve"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/BF00216210","article-title":"Preliminary observations of satellite cells in undamaged fibres of the rat soleus muscle assaulted by a snake-venom toxin","volume":"230","author":"Harris","year":"1983","journal-title":"Cell Tissue Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0041-0101(97)00112-8","article-title":"Injury and recovery of fast and slow skeletal muscle fibers affected by ACL myotoxin isolated from Agkistrodon contortrix laticinctus (Broad-Banded copperhead) venom","volume":"36","author":"Morini","year":"1998","journal-title":"Toxicon"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.toxicon.2005.02.001","article-title":"Functional, cellular and molecular aspects of skeletal muscle recovery after injury induced by snake venom from Notechis scutatus scutatus","volume":"45","author":"Vignaud","year":"2005","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1768-322X.1988.tb00719.x","article-title":"Regeneration of muscles after cardiotoxin injury. I. Cytological aspects","volume":"62","author":"Couteaux","year":"1988","journal-title":"Biol. Cell"},{"key":"ref_78","first-page":"211","article-title":"Degenerative and regenerative changes in murine skeletal muscle after injection of venom from the snake Bothrops asper: A histochemical and immunocytochemical study","volume":"72","author":"Arce","year":"1991","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/S0041-0101(02)00166-6","article-title":"Acute local nerve lesions induced by Bothrops jararacussu snake venom","volume":"40","author":"Marques","year":"2002","journal-title":"Toxicon"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/0041-0101(84)90077-1","article-title":"Muscle necrosis and regeneration after envenomation by Bothrops jararacussu snake venom","volume":"22","author":"Queiroz","year":"1984","journal-title":"Toxicon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1590\/S0036-46651984000500004","article-title":"Histopathological changes caused by venom of urutu snake (Bothrops alternatus) in mouse skeletal muscle","volume":"26","author":"Queiroz","year":"1984","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_82","first-page":"257","article-title":"Muscular regeneration after myonecrosis induced by Bothrops jararacussu snake venom from Argentina","volume":"25","author":"Teibler","year":"2001","journal-title":"Biocell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.toxicon.2004.08.007","article-title":"Insights into the loss of muscle mass following B. jararacussu venom in mice","volume":"44","author":"Vomero","year":"2004","journal-title":"Toxicon"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jprot.2014.02.020","article-title":"Venomous snakes of Costa Rica: Biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics","volume":"105","author":"Lomonte","year":"2014","journal-title":"J. Proteomics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.jprot.2011.03.026","article-title":"Key events in microvascular damage induced by snake venom hemorrhagic metalloproteinases","volume":"74","author":"Escalante","year":"2011","journal-title":"J. Proteomics"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Escalante, T., Rucavado, A., Herrera, C., and Fox, J.W. (2016). A Comprehensive View of the Structural and Functional Alterations of Extracellular Matrix by Snake Venom Metalloproteinases (SVMPs): Novel Perspectives on the Pathophysiology of Envenoming. Toxins, 8.","DOI":"10.3390\/toxins8100304"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1038\/jid.2008.118","article-title":"Skin Pathology Induced by Snake Venom Metalloproteinase: Acute Damage, Revascularization, and Re-epithelization in a Mouse Ear Model","volume":"128","author":"Escalante","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1006\/exmp.1995.1042","article-title":"Local Tissue Damage Induced by BaP1, a Metalloproteinase Isolated from Bothrops asper (Terciopelo) Snake Venom","volume":"63","author":"Rucavado","year":"1995","journal-title":"Exp. Mol. Pathol."},{"key":"ref_89","first-page":"401","article-title":"Pathogenesis of hemorrhage induced by rattlesnake venom. An electron microscopic study","volume":"76","author":"Ownby","year":"1974","journal-title":"Am. J. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0041-0101(85)90158-8","article-title":"Pathological changes in muscle caused by haemorrhagic and proteolytic factors from Bothrops jararaca snake venom","volume":"23","author":"Queiroz","year":"1985","journal-title":"Toxicon"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Nagaraju, S., Kemparaju, K., and Girish, K. (2009). Hyaluronidases, a Neglected Class of Glycosidases from Snake Venom. Handbook of Venoms and Toxins of Reptiles, CRC Press.","DOI":"10.1201\/9781420008661.ch11"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.toxicon.2005.02.029","article-title":"Hemorrhage induced by snake venom metalloproteinases: Biochemical and biophysical mechanisms involved in microvessel damage","volume":"45","author":"Rucavado","year":"2005","journal-title":"Toxicon"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.toxicon.2005.08.013","article-title":"Microvessel damage by B. jararacussu snake venom: Pathogenesis and influence on muscle regeneration","volume":"46","author":"Marques","year":"2005","journal-title":"Toxicon"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1021\/pr900489m","article-title":"Wound exudate as a proteomic window to reveal different mechanisms of tissue damage by snake venom toxins","volume":"8","author":"Escalante","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Escalante, T., Ortiz, N., Rucavado, A., Sanchez, E.F., Richardson, M., Fox, J.W., and Guti\u00e9rrez, J.M. (2011). Role of collagens and perlecan in microvascular stability: Exploring the mechanism of capillary vessel damage by snake venom metalloproteinases. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028017"},{"key":"ref_96","first-page":"538","article-title":"Morphology of local tissue damage in experimental snake envenomation","volume":"52","author":"Homma","year":"1971","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0344-0338(11)81039-3","article-title":"Towards Understanding Skeletal Muscle Regeneration","volume":"187","author":"Grounds","year":"1991","journal-title":"Pathol. Res. Pract."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11010-013-1952-8","article-title":"Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration","volume":"390","author":"Chaillou","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/mus.10453","article-title":"Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom","volume":"28","author":"Teixeira","year":"2003","journal-title":"Muscle Nerve"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1006\/exmp.1995.1004","article-title":"Skeletal muscle necrosis and regeneration after injection of BaH1, a hemorrhagic metalloproteinase isolated from the venom of the snake Bothrops asper (Terciopelo)","volume":"62","author":"Romero","year":"1995","journal-title":"Exp. Mol. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9856","DOI":"10.1073\/pnas.92.21.9856","article-title":"Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C\/EBP alpha","volume":"92","author":"Hu","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0002-9440(10)63188-4","article-title":"Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: A key event in muscle fibrogenesis","volume":"164","author":"Li","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1021\/pr101208f","article-title":"Proteomics of wound exudate in snake venom-induced pathology: Search for biomarkers to assess tissue damage and therapeutic success","volume":"10","author":"Rucavado","year":"2011","journal-title":"J. Proteom. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"156","DOI":"10.7150\/ijbs.10283","article-title":"Effects of nitric oxide on notexin-induced muscle inflammatory responses","volume":"11","author":"Liu","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.toxicon.2006.05.008","article-title":"l-arginine enhances muscle regeneration after experimental envenomation by B. jararacussu: A future for nitric oxide-based therapy?","volume":"48","author":"Neto","year":"2006","journal-title":"Toxicon"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.toxicon.2009.04.006","article-title":"Treatment with an anti-inflammatory drug is detrimental for muscle regeneration at Bothrops jararacussu envenoming: An experimental study","volume":"54","author":"Vomero","year":"2009","journal-title":"Toxicon"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Lesault, P.-F., Theret, M., Magnan, M., Cuvellier, S., Niu, Y., Gherardi, R.K., Tremblay, J.P., Hittinger, L., and Chazaud, B. (2012). Macrophages improve survival, proliferation and migration of engrafted myogenic precursor cells into MDX skeletal muscle. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046698"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1080\/15287391003751729","article-title":"Nandrolone stimulates MyoD expression during muscle regeneration in the condition of myonecrosis induced by Bothrops jararacussu venom poisoning","volume":"73","author":"Gallacci","year":"2010","journal-title":"J. Toxicol. Environ. Health. A"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/gerona\/gls083","article-title":"Testosterone improves the regeneration of old and young mouse skeletal muscle","volume":"68","author":"Serra","year":"2013","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10439-013-0757-y","article-title":"Ultrasound modulates the inflammatory response and promotes muscle regeneration in injured muscles","volume":"41","author":"Nagata","year":"2013","journal-title":"Ann. Biomed. Eng."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1590\/S0100-879X2012007500033","article-title":"Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom","volume":"45","author":"Tomaz","year":"2012","journal-title":"Br. J. Med. Biol. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s10103-011-1031-x","article-title":"GaAs 904-nm laser irradiation improves myofiber mass recovery during regeneration of skeletal muscle previously damaged by crotoxin","volume":"27","author":"Silva","year":"2012","journal-title":"Lasers Med. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1039\/c3pp50036e","article-title":"Effects of a low-level semiconductor gallium arsenide laser on local pathological alterations induced by Bothrops moojeni snake venom","volume":"12","author":"Bittencourt","year":"2013","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1177\/0363546508322886","article-title":"Improved Muscle Healing after Contusion Injury by the Inhibitory Effect of Suramin on Myostatin, a Negative Regulator of Muscle Growth","volume":"36","author":"Nozaki","year":"2008","journal-title":"Am. J. Sports Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Garg, K., Corona, B.T., and Walters, T.J. (2015). Therapeutic strategies for preventing skeletal muscle fibrosis after injury. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00087"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2217\/fca.14.76","article-title":"Mechanisms of myocardial ischemia-reperfusion injury and the cytoprotective role of minocycline: Scope and limitations","volume":"11","author":"Thind","year":"2015","journal-title":"Future Cardiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejphar.2010.03.059","article-title":"Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats","volume":"638","author":"Hu","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1017\/S0007114511002534","article-title":"Low-molecular-weight fucoidan regulates myogenic differentiation through the mitogen-activated protein kinase pathway in C2C12 cells","volume":"106","author":"Kim","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1124\/jpet.102.046144","article-title":"Low-Molecular-Weight Fucoidan Promotes Therapeutic Revascularization in a Rat Model of Critical Hindlimb Ischemia","volume":"305","author":"Luyt","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/SHK.0000000000000894","article-title":"Hydrogen Sulfide","volume":"48","author":"Jensen","year":"2017","journal-title":"Shock"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/bph.12869","article-title":"Hydrogen sulfide: Physiological properties and therapeutic potential in ischaemia","volume":"172","author":"Bos","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1177\/0363546516656823","article-title":"The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries","volume":"44","author":"Kobayashi","year":"2016","journal-title":"Am. J. Sports Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3727\/096368911X576045","article-title":"Losartan enhances the success of myoblast transplantation","volume":"21","author":"Fakhfakh","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.ajpath.2011.12.019","article-title":"Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy","volume":"180","author":"Rooney","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1016\/j.febslet.2015.10.004","article-title":"Laminin therapy for the promotion of muscle regeneration","volume":"589","author":"Riederer","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/bdrc.21005","article-title":"Biological approaches to improve skeletal muscle healing after injury and disease","volume":"96","author":"Gharaibeh","year":"2015","journal-title":"Birth Defects Res. C Embryo Today."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1111\/febs.12273","article-title":"Recent progress in satellite cell\/myoblast engraftment\u2014Relevance for therapy","volume":"280","author":"Briggs","year":"2013","journal-title":"FEBS J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"980","DOI":"10.2106\/JBJS.L.00266","article-title":"Use of an Antifibrotic Agent Improves the Effect of Platelet-Rich Plasma on Muscle Healing After Injury","volume":"95","author":"Terada","year":"2013","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Hamid, M.S.A., Yusof, A., and Mohamed Ali, M.R. (2014). Platelet-rich plasma (PRP) for acute muscle injury: A systematic review. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090538"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0041-0101(98)00145-7","article-title":"Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom","volume":"36","author":"Rojas","year":"1998","journal-title":"Toxicon"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/5\/182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:43Z","timestamp":1760194963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/5\/182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":131,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["toxins10050182"],"URL":"https:\/\/doi.org\/10.3390\/toxins10050182","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,1]]}}}