Pathogenesis of myonecrosis induced by crude venom and a myotoxin of Bothrops asper

Gutiérrez, José Marı́a; Ownby, Charlotte L.; Odell, George V.

doi:10.1016/0014-4800(84)90054-6

Cited by 134 publications

(83 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Plasma CK activity increased drastically in mice pretreated with SS and then receiving an i. m. injection of B. asper venom, refl ecting a prominent myonecrotic process (Fig. 3A), as has been previously described [28]. No signifi cant variations in the plasma CK activity was observed in mice pretreated with either L-NAME, D-NAME or aminoguanidine, despite a trend of increment in myonecrosis in mice receiving L-NAME (Fig.…”

Section: Inhibition Of Venom-induced Local Effectssupporting

confidence: 78%

“…Previous studies had shown that other participants of the infl ammatory reaction, i. e. neutrophils, matrix metalloproteinases and the cytokines TNF-α, IL-1β and IL-6, are not directly involved in acute myonecrosis in a similar experimental model of B. asper envenomation [14,18,26]. Hence, local myonecrosis induced by this venom very likely depends on the direct toxic effects of myotoxic phospholipases A 2 [5,28] and hemorrhagic metalloproteinases [38,39]. The former infl ict muscle damage by directly affecting the integrity of skeletal muscle cell plasma membrane [7,28], whereas myonecrosis induced by hemorrhagic proteinases is likely to be secondary to the ischemia resultant in the tissue from the deleterious effects on blood supply [39].…”

Section: Discussionmentioning

confidence: 99%

“…Hence, local myonecrosis induced by this venom very likely depends on the direct toxic effects of myotoxic phospholipases A 2 [5,28] and hemorrhagic metalloproteinases [38,39]. The former infl ict muscle damage by directly affecting the integrity of skeletal muscle cell plasma membrane [7,28], whereas myonecrosis induced by hemorrhagic proteinases is likely to be secondary to the ischemia resultant in the tissue from the deleterious effects on blood supply [39]. It is necessary to carry out a more comprehensive assessment on the role of NO in myotoxicity induced by a variety of myotoxic proteins present in other snake and arthropod venoms.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

2006

View full text Add to dashboard Cite

Abstract.Objective: To assess the role of nitric oxide in the most relevant local and systemic manifestations in mice injected with the venom of the snake Bothrops asper. Mice were pretreated with nitric oxide synthase inhibitors, and the modifi cations of the pathological effects induced by the venom were tested. Results: Inhibition of NO synthesis did not affect acute local myonecrosis and hemorrhage in muscle tissue upon intramuscular injection of venom. Local footpad edema was reduced in mice pretreated with the NO synthase inhibitor L-NAME, and a reduction in the extent of infl ammatory infi ltrate in muscle tissue was observed after envenomation in mice pretreated with L-NAME and aminoguanidine. The most pronounced effect of NOS inhibition by L-NAME was an increment in the lethal activity of the venom, when injected by the intraperitoneal route. Conclusion: Nitric oxide does not seem to play a signifi cant role in the local acute pathological alterations (hemorrhage and myonecrosis) induced by B. asper venom in mice, although it contributes to edema and infl ammatory infi ltrate. Nitric oxide exerts a protective role in the systemic pathophysiological manifestations leading to lethality.

show abstract

Section: Inhibition Of Venom-induced Local Effectssupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

2006

View full text Add to dashboard Cite

show abstract

“…Suspensions of washed erythrocytes were prepared in phosphate-buffered saline (PBS) using standard procedures whereas the indirect hemolytic activity was assayed in a mixture containing venom or PLA 2 , hen egg-yolk lecithin and erythrocytes, essentially as described by Gutiérrez et al. (10). The relationship between venom concentration and hemolysis was investigated in sheep erythrocytes.…”

Section: Assay For Hemolytic Activitymentioning

confidence: 99%

In vitro hemolytic activity of Bothrops lanceolatus (fer-de-lance) venom

Martins¹,

Araújo²,

Bon³

et al. 2009

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

Bothrops lanceolatus venom contains a variety of enzymatic and biological activities. The present work investigated the hemolytic activity of this venom and its phospholipase A 2 (PLA 2 ). Bothrops lanceolatus venom (6.7 µg/mL) caused indirect hemolysis of cow, horse, rat and sheep erythrocytes, with horse erythrocytes being the most sensitive; no direct hemolysis was observed. Hemolysis in sheep erythrocytes was concentration-dependent (5-11.7 µg/mL) and markedly attenuated by heating the venom for 30 minutes at ≥ 40°C and by the PLA 2 inhibitor p-bromophenacyl bromide. An acidic PLA 2 (5 µg/mL) purified from B. lanceolatus venom also caused hemolysis. This PLA 2 showed immunoprecipitin lines with antivenom against B. lanceolatus, which suggests that the enzymatic and hemolytic activities of this enzyme may be neutralized during antivenom therapy. These results indicate that B. lanceolatus venom and its PLA 2 can cause hemolysis in vitro.

show abstract

“…myotoxic PLA 2 s in muscle cells is similar, including early cell membrane destruction (Gopalakrishnakone et al, 1984;Gutierrez et al, 1984) that leads to similar histological signals of lesion, specific intracellular pathways might also be activated, leading to different outcomes at the molecular level. These differential effects might explain differences in potency, site of action (muscle vs. nervous system) and extent of myotoxicity (local vs. systemic).…”

Section: Discussionmentioning

confidence: 99%

Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Miyabara¹,

Baptista²,

Lomonte³

et al. 2006

Comparative Biochemistry and Physiology Part C: Toxicology &

View full text Add to dashboard Cite

Previous studies have shown that calcineurin activity plays a critical role in the myotoxic activity induced by crotoxin (CTX), a group II phospholipase A 2 (PLA 2 ) with neurotoxic and myotoxic actions. In order to address whether calcineurin is also important for the activity of nonneurotoxic group II PLA 2 myotoxins we have compared the effects of calcineurin inhibition on the myotoxic capacity of CTX and the nonneurotoxic PLA 2 s, myotoxin II (Mt II) and myotoxin III (Mt III) from Bothrops asper venom. Rats were treated with cyclosporin A (CsA) or FK506, calcineurin inhibitors, and received an intramuscular injection of either CTX, Mt II or Mt III into the tibialis anterior. Animals were killed 24 h after injection of toxins. Tibialis anterior was removed and stored in liquid nitrogen. Myofibers in culture were also treated with CsA or FK506 and exposed to CTX, Mt II and Mt III. It was observed that, in contrast to CTX, CsA and FK506 do not attenuate myotoxic effects induced by both Mt II and Mt III in vivo and in vitro. The results of the present study suggest that calcineurin is not essential for the myotoxic activity of Mt II and Mt III, indicating that distinct intracellular pathways might be involved in myonecrosis induced by neurotoxic CTX and non-neurotoxic Bothrops sp. PLA 2 myotoxins. Alternatively, calcineurin dependent fast fiber type shift might render the muscle resistant to the action of CTX, without affecting its susceptibility to Bothrops sp. myotoxins.

show abstract

Pathogenesis of myonecrosis induced by crude venom and a myotoxin of Bothrops asper

Cited by 134 publications

References 18 publications

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

In vitro hemolytic activity of Bothrops lanceolatus (fer-de-lance) venom

Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Contact Info

Product

Resources

About