Traces of Bothrops snake venoms in necrotic muscle preclude myotube formation in vitro

Velde, Andrea Carolina Van de; Fusco, Luciano; Echeverría, Silvina M; Sasovsky, Daniela J; Leiva, Laura; Gutiérrez, José Marı́a; Bustillo, Soledad

doi:10.1016/j.toxicon.2022.03.008

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Incomplete myotube formation was also evidenced in C2C12 myoblasts following exposure to murine muscle homogenates obtained from envenomed mice by the venom of Bothrops asper (the most medically important pit viper in Central America) 39 . The long-term presence of toxins in muscle during different stages of regeneration has been detected in previous studies with viper venoms, and this impedes the complete regeneration of the muscle 40 . Atrophy assays showed that the control myotubes were larger than the ones treated with venoms.…”

Section: Discussionmentioning

confidence: 82%

Differential effects of the venoms of Russell’s viper and Indian cobra on human myoblasts

Bin Haidar,

Almeida,

Williams

et al. 2024

Sci Rep

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Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell’s viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian ‘Big Four’ snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell’s viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell’s viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.

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Section: Discussionmentioning

confidence: 82%

Differential effects of the venoms of Russell’s viper and Indian cobra on human myoblasts

Bin Haidar,

Almeida,

Williams

et al. 2024

Sci Rep

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“…The action and temporal presence of these myotoxins must also be considered in this speculative view. Previous studies have shown the long-lasting presence of SVMP, which leads to continuous ECM degradation and haemorrhagic effects [ 11 , 52 ]. The temporal action of cardiotoxin is in line with the restoration of muscle architecture and complete removal of the signs of intramuscular bleeding [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Intramuscular Bleeding and Formation of Microthrombi during Skeletal Muscle Damage Caused by a Snake Venom Metalloprotease and a Cardiotoxin

Sonavane,

Almeida,

Rajan

et al. 2023

Toxins

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The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining the underlying mechanisms of muscle degeneration/regeneration following snakebites is critical to developing better strategies to tackle this issue. Here, we analysed intramuscular bleeding and thrombosis in muscle injuries induced by two different snake venom toxins (CAMP—Crotalus atrox metalloprotease (a PIII metalloprotease from the venom of this snake) and a three-finger toxin (CTX, a cardiotoxin from the venom of Naja pallida)). Classically, these toxins represent diverse scenarios characterised by persistent muscle damage (CAMP) and successful regeneration (CTX) following acute damage, as normally observed in envenomation by most vipers and some elapid snakes of Asian, Australasian, and African origin, respectively. Our immunohistochemical analysis confirmed that both CAMP and CTX induced extensive muscle destruction on day 5, although the effects of CTX were reversed over time. We identified the presence of fibrinogen and P-selectin exposure inside the damaged muscle sections, suggesting signs of bleeding and the formation of platelet aggregates/microthrombi in tissues, respectively. Intriguingly, CAMP causes integrin shedding but does not affect any blood clotting parameters, whereas CTX significantly extends the clotting time and has no impact on integrin shedding. The rates of fibrinogen clearance and reduction in microthrombi were greater in CTX-treated muscle compared to CAMP-treated muscle. Together, these findings reveal novel aspects of venom-induced muscle damage and highlight the relevance of haemostatic events such as bleeding and thrombosis for muscle regeneration and provide useful mechanistic insights for developing better therapeutic interventions.

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The anti-myotoxic effects and mechanisms of Sinonatrix annularis serum and a novel plasma metalloproteinase inhibitor towards Deinagkistrodon acutus envenomation

Fu,

Cao,

Tang

et al. 2023

Toxicology Letters

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Traces of Bothrops snake venoms in necrotic muscle preclude myotube formation in vitro

Cited by 3 publications

References 42 publications

Differential effects of the venoms of Russell’s viper and Indian cobra on human myoblasts

Differential effects of the venoms of Russell’s viper and Indian cobra on human myoblasts

Intramuscular Bleeding and Formation of Microthrombi during Skeletal Muscle Damage Caused by a Snake Venom Metalloprotease and a Cardiotoxin

The anti-myotoxic effects and mechanisms of Sinonatrix annularis serum and a novel plasma metalloproteinase inhibitor towards Deinagkistrodon acutus envenomation

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