Systemic skeletal muscle necrosis induced by crotoxin

Salvini, Tania F.; Amaral, André Capaldo; Miyabara, Elen Haruka; Turri, José Antonio Orellana; D’Anella, Pascal; Araújo, Heloísa Sobreiro Selistre de

doi:10.1016/s0041-0101(00)00245-2

Cited by 54 publications

(40 citation statements)

References 26 publications

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“…Furthermore, knockout mice for iNOS develop less muscle injury in a model of ischemia-reperfusion [35]. Regarding snake venoms, pre-treatment with L-NAME drastically abrogated the extent of myonecrosis induced by crotoxin [21], a highly potent neurotoxic and myotoxic phospholipase A 2 responsible of the paralysis and systemic myotoxicity characteristic of envenomations by the South American rattlesnake Crotalus durissus terrifi cus [36,37]. On these grounds, it was of interest to assess if NO plays a role in B. asper venom-induced local myonecrosis.…”

Section: Discussionmentioning

confidence: 99%

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

2006

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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.

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Section: Discussionmentioning

confidence: 99%

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

2006

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“…Graça et al (2006) submeteram quatro bovinos ao decúbito experimental por seis horas e verificaram, 18 horas após o início do decúbito, aumentos de creatinaquinase de aproximadamente 130 vezes os valores obtidos antes do início da contenção. Devemos lembrar que além da ação miotóxica, os animais de nosso experimento foram submetidos à contenção mecânica, punções venosas para coleta de sangue e permaneceram em decúbito por períodos que variaram entre 2 horas 10 minutos e 9 dias ou seja, os resultados obtidos em estudos ligados ao decúbito permanente em bovinos, indicam que os valores obtidos em nosso experimento não sugerem um quadro acentuado de necrose muscular, o que é confirmado pela ação seletiva da miotoxina sobre as fibras musculares, verificada histologicamente (Hudelson & Hudelson 1995b, Salvini et al 2001.…”

Section: Patologia Clínicaunclassified

Aspectos clínico-patológicos e laboratoriais do envenenamento crotálico experimental em bovinos

et al. 2008

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Pesq. Vet. Bras. 28(6):261-270, junho 2008 RESUMO.-Reproduziu-se experimentalmente o envenenamento crotálico, através da inoculação, por via subcutânea, do veneno de Crotalus durissus terrificus (cascavel sul-americana) em dez bovinos mestiços. Dois animais foram utilizados como controle. O bovino que recebeu dose de 0,03mg/kg de peso corporal, morreu 7h40min após a inoculação. A dose de 0,015mg/kg causou a morte em quatro de sete bovinos inoculados, enquanto os dois animais que receberam 0,0075mg/kg adoeceram discretamente e se recuperaram. Os sintomas tiveram início entre 1h30min e 13h45min após a inoculação. A evolução oscilou entre 5h25min e 45h para os animais que morreram e entre 33h15min e 17 dias entre os animais que se recuperaram. Os principais sinais nervosos observados foram diminuição da resposta aos estímulos Crotalus poisoning was experimentally reproduced by subcutaneous inoculation of Crotalus durissus terrificus (South American rattlesnake) venom into 10 clinically healthy mixed bred 12 to 36-month-old cattle, weighing 125 to 449 kg. Two animals were used as controls. The animal that received a dose of 0.03mg/kg body weight died 7h40min after inoculation. A 0.015mg/kg dose provoked death in 4 out of 7 young oxen. Two animals given 0.0075mg/kg became slightly sick and recovered. Onset of symptoms occurred from 1h30min to 13h45min after inoculation. The clinical course varied from 5h25min to 45h for animals that died, and from 33h15min to 17 days for animals that recovered. The main nervous signs observed were diminished response to external stimuli, hypotonic reflexes, dragging of the hooves, apathy, difficulties in moving around obstacles, ocular globe paralysis, lateral and sternal decubitus, and tongue paralysis. Adipsia and sometimes petechiae in the conjunctival and vaginal mucosa were observed. A slight to moderate increase in bleeding time was noted in 6 animals, and a moderate increase in partial thromboplastin time was found in 7 others. Moderate leukocytosis with neutrophilia, relative lymphopenia, eosinopenia, and monocytosis was found. There was a significant increase in creatine kinase serum levels of a ten-fold order. No significant alterations were revealed by urinalysis. Necropsy revealed minimal edema at the inoculation site, few petechiae and equimoses in the epicardium, omentum, biliary vesicle and bladder mucosa of some animals. Histopathological examination revealed necrosis (hyalinization) of groups or isolated myocytes in different muscles examined, both near and far from the inoculation site, in all animals. The diagnosis of Crotalus poisoning and its differentiation from diseases causing paralysis and muscular necrosis in cattle in Brazil are discussed.

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“…(c) Since calcineurin is involved in muscle fiber type determination (Chin et al, 1998), our results may reflect the different specificity of these PLA 2 s toward different fiber types. CTX and other neurotoxic PLA 2 myotoxins have preference for type I fibers (Harris et al, 1975;Salvini et al, 2001), whereas types I and II fibers present a similar susceptibility to a viperid Lys-49 myotoxic PLA 2 (Morini et al, 1998). From this perspective, the effect of calcineurin would not depend on activation of intracellular degenerative mechanisms, but instead would be related with fiber type determination.…”

Section: Discussionmentioning

confidence: 99%

“…PLA 2 myotoxins also have differences regarding their ability to induce local and systemic muscle damage (Gutierrez and Ownby, 2003). CTX is able to induce muscle damage not only in the injected muscle (local myotoxicity), but also in muscles remotely located (systemic myotoxicity) (Salvini et al, 2001). In contrast, Mt II and Mt III only induce local myotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…A well-characterized example of neurotoxic sPLA 2 myotoxin is crotoxin (CTX), a venom component of the South American rattlesnake Crotalus durissus terrificus (Hendon and Fraenkel-Conrat, 1971;Mebs and Ownby, 1990;Salvini et al, 2001). Among the non-neurotoxic sPLA 2 myotoxins, two different types are currently described: the "classical" Asp-49 PLA 2 s, which catalyze the hydrolysis of the ester Comparative Biochemistry and Physiology, Part C 143 (2006) 284 -294 www.elsevier.com/locate/cbpc bond in the sn-2 position of glycerophospholipids in a Ca 2+ dependent manner; and the "variant" Lys-49 PLA 2 s which have been described as devoid of enzymatic activity due to replacement of Asp-49 by Lys, together with other modifications in the calcium-binding loop (Lomonte et al, 2003b).…”

Section: Introductionmentioning

confidence: 99%

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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 &

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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.

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Systemic skeletal muscle necrosis induced by crotoxin

Cited by 54 publications

References 26 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

Aspectos clínico-patológicos e laboratoriais do envenenamento crotálico experimental em bovinos

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

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