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Journal of Muscle Research and Cell Motility

, Volume 40, Issue 3–4, pp 291–297 | Cite as

Biotoxins in muscle regeneration research

  • Mohamed A. A. MahdyEmail author
Reviews

Abstract

Skeletal muscles are characterized by their unique regenerative capacity following injury due to the presence of muscle precursor cells, satellite cells. This characteristic allows researchers to study muscle regeneration using experimental injury models. These injury models should be stable and reproducible. Variety of injury models have been used, among which the intramuscular injection of myotoxic biotoxins is considered the most common and widespread method in muscle regeneration research. By using isolated biotoxins, researchers could induce acute muscle damage and regeneration in a controlled and reproducible manner. Therefore, it is considered an easy method for inducing muscle injury in order to understand the different mechanisms involved in muscle injuries and tissue response following injury. However, different toxins and venoms have different compositions and subsequently the possible effects of these toxins on skeletal muscle vary according to their composition. Moreover, regeneration of injured muscle by venoms and toxins varies according to the target of toxin or venom. Therefore, it is essential for researcher to be aware of the mechanism and possible target of toxin-induced injury. The current paper provides an overview of the biotoxins used in skeletal muscle research.

Keywords

Biotoxins Snake venom Muscle injury Regeneration 

Notes

Compliance with ethical standards

Conflict of interest

The author declare that he has no conflict of interest.

Ethical approval

The authors declare that this paper complies with ethical standards in publishing.

References

  1. Akpulat U, Onbasilar I, Kocaefe YC (2016) Tenotomy immobilization as a model to investigate skeletal muscle fibrosis (with emphasis on Secreted frizzled-related protein 2). Physiol Genomics 48:397–408PubMedGoogle Scholar
  2. Angulo Y, Lomonte B (2009) Biochemistry and toxicology of toxins purified from the venom of the snake Bothrops asper. Toxicon 54:949–957PubMedGoogle Scholar
  3. Baghdadi MB, Tajbakhsh S (2018) Regulation and phylogeny of skeletal muscle regeneration. Dev Biol 433:200–209PubMedGoogle Scholar
  4. Barbier J, Popoff MR, Molgo J (2004) Degeneration and regeneration of murine skeletal neuromuscular junctions after intramuscular injection with a sublethal dose of Clostridium sordellii lethal toxin. Infect Immun 72:3120–3128PubMedPubMedCentralGoogle Scholar
  5. Brin MF (1997) Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl 6:S146–S168PubMedGoogle Scholar
  6. Carlson B (2008) Muscle regeneration in animal models. In: Schiaffino S, Partridge T (eds) Skeletal muscle repair and regeneration, vol 3. Advances in muscle research. Springer, Dordrecht, pp 163–180Google Scholar
  7. Carlson BM (2014) The biology of long-term denervated skeletal muscle. Eur J Transl Myol 24:3293PubMedPubMedCentralGoogle Scholar
  8. Chan YS, Cheung RCF, Xia L, Wong JH, Ng TB, Chan WY (2016) Snake venom toxins: toxicity and medicinal applications. Appl Microbiol Biotechnol 100:6165–6181PubMedGoogle Scholar
  9. Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238PubMedGoogle Scholar
  10. Chen C-M, Stott NS, Smith HK (2002) Effects of botulinum toxin A injection and exercise on the growth of juvenile rat gastrocnemius muscle. J Appl Physiol 93:1437–1447PubMedGoogle Scholar
  11. Cull-Candy SG, Fohlman J, Gustavsson D, Lullmann-Rauch R, Thesleff S (1976) The effects of taipoxin and notexin on the function and fine structure of the murine neuromuscular junction. Neuroscience 1:175–180PubMedGoogle Scholar
  12. Czerwinska AM, Streminska W, Ciemerych MA, Grabowska I (2012) Mouse gastrocnemius muscle regeneration after mechanical or cardiotoxin injury. Folia Histochem Cytobiol 50:144–153PubMedGoogle Scholar
  13. Dixon RW, Harris JB (1996) Myotoxic activity of the toxic phospholipase, notexin, from the venom of the Australian tiger snake. J Neuropathol Exp Neurol 55:1230–1237PubMedGoogle Scholar
  14. Fathi B, Harvey AL, Rowan EG (2013) The effect of temperature on the effects of the phospholipase A(2) neurotoxins beta-bungarotoxin and taipoxin at the neuromuscular junction. Toxicon 70:86–89PubMedGoogle Scholar
  15. Ferreira MJ, Lima C, Lopes-Ferreira M (2014) Anti-inflammatory effect of Natterins, the major toxins from the Thalassophryne nattereri fish venom is dependent on TLR4/MyD88/PI3K signaling pathway. Toxicon 87:54–67PubMedGoogle Scholar
  16. Frick CG, Richtsfeld M, Sahani ND, Kaneki M, Blobner M, Martyn JA (2007) Long-term effects of botulinum toxin on neuromuscular function. Anesthesiology 106:1139–1146PubMedGoogle Scholar
  17. Fukada S, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, Ito T, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H (2010) Genetic background affects properties of satellite cells and mdx phenotypes. Am J Pathol 176:2414–2424PubMedPubMedCentralGoogle Scholar
  18. Garcia Denegri ME, Teibler GP, Marunak SL, Hernandez DR, Acosta OC, Leiva LC (2016) Efficient muscle regeneration after highly haemorrhagic Bothrops alternatus venom injection. Toxicon 122:167–175PubMedGoogle Scholar
  19. Gawade SP (2004) Snake venom neurotoxins: pharmacological classification. Toxin Rev 23:37–96Google Scholar
  20. Gordon T, Tyreman N, Raji MA (2011) The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci 31:5325PubMedPubMedCentralGoogle Scholar
  21. Grasa J, Pérez-Ruíz A, Muñoz MJ, Soteras F, Bobadilla Muñoz M, Baraibar Churio A, Prósper F, Calvo B (2018) A quantitative method for the detection of muscle functional active and passive behavior recovery in models of damage-regeneration. Proc IMechE L 0:1–10Google Scholar
  22. Gutierrez JM, Ownby CL (2003) Skeletal muscle degeneration induced by venom phospholipases A2: insights into the mechanisms of local and systemic myotoxicity. Toxicon 42:915–931PubMedGoogle Scholar
  23. Gutierrez JM, Ownby CL, Odell GV (1984) Skeletal muscle regeneration after myonecrosis induced by crude venom and a myotoxin from the snake Bothrops asper (Fer-de-Lance). Toxicon 22:719–731PubMedGoogle Scholar
  24. Gutierrez JM, Arce V, Brenes F, Chaves F (1990) Changes in myofibrillar components after skeletal muscle necrosis induced by a myotoxin isolated from the venom of the snake Bothrops asper. Exp Mol Pathol 52:25–36PubMedGoogle Scholar
  25. Gutierrez JM, Escalante T, Hernandez R, Gastaldello S, Saravia-Otten P, Rucavado A (2018) Why is skeletal muscle regeneration impaired after myonecrosis induced by viperid snake venoms? Toxins (Basel) 10:182Google Scholar
  26. Gutiérrez JM, Rucavado A, Chaves F, Díaz C, Escalante T (2009) Experimental pathology of local tissue damage induced by Bothrops asper snake venom. Toxicon 54:958–975PubMedGoogle Scholar
  27. Hardy D, Besnard A, Latil M, Jouvion G, Briand D, Thepenier C, Pascal Q, Guguin A, Gayraud-Morel B, Cavaillon JM, Tajbakhsh S, Rocheteau P, Chretien F (2016) Comparative study of injury models for studying muscle regeneration in mice. PLoS ONE 11:e0147198PubMedPubMedCentralGoogle Scholar
  28. Harris JB (2003) Myotoxic phospholipases A2 and the regeneration of skeletal muscles. Toxicon 42:933–945PubMedGoogle Scholar
  29. Harris J (2009) Neuromuscular junction (NMJ): a target for natural and environmental toxins in humans, pp. 539–549Google Scholar
  30. Harris JB, Johnson MA, Karlsson E (1975) Pathological responses of rat skeletal muscle to a single subcutaneous injection of a toxin isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus. Clin Exp Pharmacol Physiol 2:383–404Google Scholar
  31. Harris JB, Grubb BD, Maltin CA, Dixon R (2000) The neurotoxicity of the venom phospholipases a2, notexin and taipoxin. Exp Neurol 161:517–526PubMedGoogle Scholar
  32. Harris JB, Vater R, Wilson M, Cullen MJ (2003) Muscle fibre breakdown in venom-induced muscle degeneration. J Anat 202:363–372PubMedPubMedCentralGoogle Scholar
  33. Hassan SM, Badawoud MH, Al-Hayani AA (2012) Structural alterations induced by botulinum toxin injection in juvenile versus adult rat muscle. Saudi Med J 33:17–23PubMedGoogle Scholar
  34. Hernández R, Cabalceta C, Saravia-Otten P, Chaves A, Gutiérrez JM, Rucavado A (2011) Poor regenerative outcome after skeletal muscle necrosis induced by Bothrops asper venom: alterations in microvasculature and nerves. PLoS ONE 6:e19834PubMedPubMedCentralGoogle Scholar
  35. Herrera C, Macêdo JKA, Feoli A, Escalante T, Rucavado A, Gutiérrez JM, Fox JW (2016a) 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:e0004599PubMedPubMedCentralGoogle Scholar
  36. Herrera C, Voisin M-B, Escalante T, Rucavado A, Nourshargh S, Gutiérrez JM (2016b) Effects of pi and piii snake venom haemorrhagic metalloproteinases on the microvasculature: a confocal microscopy study on the mouse cremaster muscle. PLoS ONE 11:e0168643PubMedPubMedCentralGoogle Scholar
  37. Horie M, Enomoto M, Shimoda M, Okawa A, Miyakawa S, Yagishita K (2014) Enhancement of satellite cell differentiation and functional recovery in injured skeletal muscle by hyperbaric oxygen treatment. J Appl Physiol (1985) 116:149–155Google Scholar
  38. Inagi K, Connor NP, Schultz E, Ford CN, Cook CH, Heisey DM (1999) Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx. Otolaryngol Head Neck Surg 120:876–883PubMedGoogle Scholar
  39. Järvinen TAH, Järvinen M, Kalimo H (2013) Regeneration of injured skeletal muscle after the injury. Muscles Ligaments Tendons J 3:337–345PubMedGoogle Scholar
  40. Johnson B, Mastnjak R, Resnick IG (2001) Safety and health considerations for conducting work with biological toxins. Appl Biosaf 6:117–135Google Scholar
  41. Kim CS, Jang WS, Son IP, Nam SH, Kim YI, Park KY, Kim BJ, Kim MN (2013) Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle. Hum Exp Toxicol 32:914–920PubMedGoogle Scholar
  42. Kozlovac JP, Hawley RJ (2006) Biological toxins: safety and science. Biological Safety. American Society of Microbiology, Washington, DCGoogle Scholar
  43. Kumar TKS, Pandian SK, Srisailam S, Yu C (1998) Structure and function of snake venom cardiotoxins. J Toxicol 17:183–211Google Scholar
  44. Kuruppu S, Smith AI, Isbister GK, Hodgson WC (2008) Neurotoxins from Australo-Papuan elapids: a biochemical and pharmacological perspective. Crit Rev Toxicol 38:73–86PubMedGoogle Scholar
  45. Langone F, Cannata S, Fuoco C, Lettieri Barbato D, Testa S, Nardozza AP, Ciriolo MR, Castagnoli L, Gargioli C, Cesareni G (2014) Metformin protects skeletal muscle from cardiotoxin induced degeneration. PLoS ONE 9:e114018PubMedPubMedCentralGoogle Scholar
  46. Lapa AJ, Albuquerque EX, Daly J (1974) An electrophysiological study of the effects of D-tubocurarine, atropine, and alpha-bungarotoxin on the cholinergic receptor in innervated and chronically denervated mammalian skeletal muscles. Exp Neurol 43:375–398PubMedGoogle Scholar
  47. Lee AS, Anderson JE, Joya JE, Head SI, Pather N, Kee AJ, Gunning PW, Hardeman EC (2013) Aged skeletal muscle retains the ability to fully regenerate functional architecture. Bioarchitecture 3:25–37PubMedPubMedCentralGoogle Scholar
  48. Liu W, Liu Y, Lai X, Kuang S (2012) Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles. Dev Biol 361:27–38PubMedGoogle Scholar
  49. Lopes-Ferreira M, Barbaro KC, Cardoso DF, Moura-Da-Silva AM, Mota I (1998) Thalassophryne nattereri fish venom: biological and biochemical characterization and serum neutralization of its toxic activities. Toxicon 36:405–410PubMedGoogle Scholar
  50. Lopes-Ferreira M, Núñez J, Rucavado A, Farsky SHP, Lomonte B, Angulo Y, Da Silva AMm, Gutiérrez JM (2001) Skeletal muscle necrosis and regeneration after injection of Thalassophryne nattereri (niquim) fish venom in mice. Int J Exp Pathol 82:55–64PubMedPubMedCentralGoogle Scholar
  51. Lopes-Ferreira M, Grund LZ, Lima C (2014) Thalassophryne nattereri fish venom: from the envenoming to the understanding of the immune system. J Venom Anim Toxins Incl Trop Dis 20:35PubMedPubMedCentralGoogle Scholar
  52. Madaro L, Passafaro M, Sala D, Etxaniz U, Lugarini F, Proietti D, Alfonsi MV, Nicoletti C, Gatto S, De Bardi M, Rojas-Garcia R, Giordani L, Marinelli S, Pagliarini V, Sette C, Sacco A, Puri PL (2018) Denervation-activated STAT3-IL-6 signalling in fibro-adipogenic progenitors promotes myofibres atrophy and fibrosis. Nat Cell Biol 20:917–927PubMedPubMedCentralGoogle Scholar
  53. Mahdy M (2018) Glycerol-induced injury as a new model of muscle regeneration. Cell Tissue Res 374:233–241PubMedGoogle Scholar
  54. Mahdy M (2019) Skeletal muscle fibrosis: an overview. Cell Tissue Res 375:575–588PubMedGoogle Scholar
  55. Mahdy MA, Lei HY, Wakamatsu J-I, Hosaka YZ, Nishimura T (2015) Comparative study of muscle regeneration following cardiotoxin and glycerol injury. Ann Anat 202:18–27PubMedGoogle Scholar
  56. Mahdy MA, Warita K, Hosaka YZ (2016) Early ultrastructural events of skeletal muscle damage following cardiotoxin-induced injury and glycerol-induced injury. Micron 91:29–40PubMedGoogle Scholar
  57. Mahdy MAA, Warita K, Hosaka YZ (2018) Glycerol induces early fibrosis in regenerating rat skeletal muscles. J Vet Med Sci 80:1646–1649PubMedPubMedCentralGoogle Scholar
  58. Mebs D, Ownby CL (1990) Myotoxic components of snake venoms: their biochemical and biological activities. Pharmacol Ther 48:223–236PubMedGoogle Scholar
  59. Mohan SK, Yu C (2007) Structure function relationships of cobrotoxin from naja naja atra. Toxin Rev 26:99–122Google Scholar
  60. Montecucco C, Gutierrez JM, Lomonte B (2008) Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action. Cell Mol Life Sci 65:2897–2912PubMedGoogle Scholar
  61. Neto HS, Marques MJ (2005) Microvessel damage by B. jararacussu snake venom: pathogenesis and influence on muscle regeneration. Toxicon 46:814–819PubMedGoogle Scholar
  62. Ownby CL, Fletcher JE, Colberg TR (1993) Cardiotoxin 1 from cobra (Naja naja atra) venom causes necrosis of skeletal muscle in vivo. Toxicon 31:697–709PubMedGoogle Scholar
  63. Pessina P, Cabrera D, Morales MG, Riquelme CA, Gutierrez J, Serrano AL, Brandan E, Munoz-Canoves P (2014) Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne muscular dystrophy. Skelet Muscle 4:7PubMedPubMedCentralGoogle Scholar
  64. Pingel J, Nielsen MS, Lauridsen T, Rix K, Bech M, Alkjaer T, Andersen IT, Nielsen JB, Feidenhansl R (2017) Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures. Sci Rep 7:14746PubMedPubMedCentralGoogle Scholar
  65. Pitschmann V, Hon Z (2016) Military importance of natural toxins and their analogs. Molecules 21:556PubMedCentralGoogle Scholar
  66. Plant DR, Colarossi FE, Lynch GS (2006) Notexin causes greater myotoxic damage and slower functional repair in mouse skeletal muscles than bupivacaine. Muscle Nerve 34:577–585PubMedGoogle Scholar
  67. Ranawaka UK, Lalloo DG, de Silva HJ (2013) Neurotoxicity in snakebite—the limits of our knowledge. PLoS Negl Trop Dis 7:e2302PubMedPubMedCentralGoogle Scholar
  68. Rodrigues Ade C, Schmalbruch H (1995) Satellite cells and myonuclei in long-term denervated rat muscles. Anat Rec 243:430–437PubMedGoogle Scholar
  69. Sanes JR (2003) The basement membrane/basal lamina of skeletal muscle. J Biol Chem 278:12601–12604PubMedGoogle Scholar
  70. Segawa M, Fukada S-i, Yamamoto Y, Yahagi H, Kanematsu M, Sato M, Ito T, Uezumi A, Si Hayashi, Miyagoe-Suzuki Y, Si Takeda, Tsujikawa K, Yamamoto H (2008) Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis. Exp Cell Res 314:3232–3244PubMedGoogle Scholar
  71. Utkin YN (2015) Animal venom studies: current benefits and future developments. World J Biol Chem 6:28–33PubMedPubMedCentralGoogle Scholar
  72. Valencia AP, Iyer SR, Spangenburg EE, Gilotra MN, Lovering RM (2017) Impaired contractile function of the supraspinatus in the acute period following a rotator cuff tear. BMC Musculoskelet Disord 18:436PubMedPubMedCentralGoogle Scholar
  73. Warrell DA (2013) Animals hazardous to humans. In: Magill AJ, Hill DR, Solomon T, Ryan ET (eds) Hunter’s tropical medicine and emerging infectious disease, 9th edn. Saunders, London, pp 938–965Google Scholar
  74. Westerlund B, Nordlund P, Uhlin U, Eaker D, Eklund H (1992) The three-dimensional structure of notexin, a presynaptic neurotoxic phospholipase A2 at 2.0 Å resolution. FEBS Lett 301:159–164PubMedGoogle Scholar
  75. Wu P, Chawla A, Spinner RJ, Yu C, Yaszemski MJ, Windebank AJ, Wang H (2014) Key changes in denervated muscles and their impact on regeneration and reinnervation. Neural Regen Res 9:1796–1809PubMedPubMedCentralGoogle Scholar
  76. Yan Z, Choi S, Liu X, Zhang M, Schageman JJ, Lee SY, Hart R, Lin L, Thurmond FA, Williams RS (2003) Highly coordinated gene regulation in mouse skeletal muscle regeneration. J Biol Chem 278:8826–8836PubMedGoogle Scholar
  77. Yang CC (1999) Cobrotoxin: structure and function. J Nat Toxins 8:221–233PubMedGoogle Scholar
  78. Yee JSP, Nanling G, Afifiyan F, Donghui M, Siew Lay P, Armugam A, Jeyaseelan K (2004) Snake postsynaptic neurotoxins: gene structure, phylogeny and applications in research and therapy. Biochimie 86:137–149Google Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Anatomy and Embryology, Faculty of Veterinary MedicineSouth Valley UniversityQenaEgypt

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