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Toxins 2018, 10(5), 182; https://doi.org/10.3390/toxins10050182

Why is Skeletal Muscle Regeneration Impaired after Myonecrosis Induced by Viperid Snake Venoms?

1
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501-2060, Costa Rica
2
Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala City 01012, Guatemala
3
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-17177, Sweden
4
Precision Medicine Research Center, Binzhou Medical University, Laishan District, Guanhai Road 346, Yantai 264003, China
*
Author to whom correspondence should be addressed.
Received: 29 March 2018 / Revised: 22 April 2018 / Accepted: 25 April 2018 / Published: 1 May 2018
(This article belongs to the Section Animal Venoms)
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Abstract

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. View Full-Text
Keywords: snake venom; myonecrosis; envenoming; muscle regeneration; vasculature; extracellular matrix; snake venom metalloproteinases; phospholipases A2 snake venom; myonecrosis; envenoming; muscle regeneration; vasculature; extracellular matrix; snake venom metalloproteinases; phospholipases A2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Gutiérrez, J.M.; Escalante, T.; Hernández, R.; Gastaldello, S.; Saravia-Otten, P.; Rucavado, A. Why is Skeletal Muscle Regeneration Impaired after Myonecrosis Induced by Viperid Snake Venoms? Toxins 2018, 10, 182.

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