Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats

Dias, Lourdes; Rodrigues, Mariana Acedo Pitocco; Rennó, André L.; Stroka, Alessandra; Inoue, Bruna Ramos; Panunto, Patrícia Costa; Melgarejo, Anibal R.; Hyslop, Stephen

doi:10.1016/j.toxicon.2016.10.001

Cited by 14 publications

(10 citation statements)

References 66 publications

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“…Envenomation by Lachesis spp. is characterized by intense local pain, oedema and necrosis (Damico et al, 2006;Ferreira et al, 2009;Damico et al, 2012), systemic myotoxicity (Fuly et al, 2000;Fuly et al, 2003;Damico et al, 2006), renal failure (Damico et al, 2007), haemorrhage and coagulopathy (Sánchez et al, 1987;Sánchez et al, 1991;Sánchez et al, 1995;Fuly et al, 1997;Rucavado et al, 1999;Estêvão-Costa et al, 2000;Torres-Huaco et al, 2013), including severe cardiovascular disorders (Diniz and Oliveira, 1992;Giovanni-De-Simone et al, 1997;Dias et al, 2016a;Dias et al, 2016b). Such effects have been associated predominantly with the presence of phospholipases A 2 (PLA 2 ) (Cordeiro et al, 2015;Diniz-Sousa et al, 2018), metalloproteases (Cordeiro et al, 2018) and serine proteases (Wiezel et al, 2019), including biologically active peptides (Graham et al, 2005;Soares et al, 2005;Sanz et al, 2008;Pla et al, 2013;Pinheiro-Júnior et al, 2018), in these venoms.…”

Section: Introductionmentioning

confidence: 99%

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

et al. 2022

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Varespladib (VPL) was primarily developed to treat inflammatory disturbances associated with high levels of serum phospholipase A2 (PLA2). VPL has also demonstrated to be a potential antivenom support agent to prevent PLA2-dependent effects produced by snake venoms. In this study, we examined the action of VPL on the coagulant, haemorrhagic and enzymatic activities of Lachesis muta rhombeata (South-American bushmaster) venom. Conventional colorimetric enzymatic assays were performed for PLA2, caseinolytic and esterasic activities; in vitro coagulant activities for prothrombin time (PT) and activated partial thromboplastin time (aPTT) were performed in rat citrated plasma through a quick timer coagulometer, whereas the dimensions of haemorrhagic haloes obtained after i.d. injections of venom in Wistar rats were determined using ImageJ software. Venom (1 mg/ml) exhibited accentuated enzymatic activities for proteases and PLA2in vitro, with VPL abolishing the PLA2 activity from 0.01 mM; VPL did not affect caseinolytic and esterasic activities at any tested concentrations (0.001–1 mM). In rat citrated plasma in vitro, VPL (1 mM) alone efficiently prevented the venom (1 mg/ml)-induced procoagulant disorder associated to extrinsic (PT) pathway, whereas its association with a commercial antivenom successfully prevented changes in both intrinsic (aPTT) and extrinsic (PT) pathways; commercial antivenom by itself failed to avoid the procoagulant disorders by this venom. Venom (0.5 mg/kg)-induced hemorrhagic activity was slightly reduced by VPL (1 mM) alone or combined with antivenom (antivenom:venom ratio 1:3 ‘v/w’) in rats, with antivenom alone producing no protective action on this parameter. In conclusion, VPL does not inhibit other major enzymatic groups of L. m. rhombeata venom, with its high PLA2 antagonize activity efficaciously preventing the venom-induced coagulation disturbances.

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Section: Introductionmentioning

confidence: 99%

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

et al. 2022

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“…Few components have been purified from L. muta rhombeata venom until now, including a L-amino acid oxidase, PLA 2 , PLB, hyaluronidase, serine protease and BPPs [ 9 , 10 , 12 , 13 ]. Although there are studies about these components, little is known about some mechanisms induced by these proteins and peptides, especially in Lachesis envenomation, since its venom is difficult to obtain and is hard to keep bushmasters in captivity [ 5 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Purification and enzymatic characterization of a novel metalloprotease from Lachesis muta rhombeata snake venom

Cordeiro

Coutinho

Wiezel

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundLachesis muta rhombeata (Lmr) is the largest venomous snake in Latin America and its venom contains mainly enzymatic components, such as serine and metalloproteases, L-amino acid oxidase and phospholipases A2. Metalloproteases comprise a large group of zinc-dependent proteases that cleave basement membrane components such as fibronectin, laminin and collagen type IV. These enzymes are responsible for local and systemic changes, including haemorrhage, myonecrosis and inflammation. This study aimed the isolation and enzymatic characterization of the first metalloprotease (Lmr-MP) from Lmr venom (LmrV).Methods and resultsLmr-MP was purified through two chromatographic steps and submitted to enzymatic characterization. It showed proteolytic activity on azocasein with maximum activity at pH 7.0–9.0. It was inhibited by EDTA (a metal chelator that removes zinc, which is essential for enzymatic activity) and no effect was observed with PMSF, iodoacetic acid or pepstatin (inhibitors of serine, cysteine and aspartyl proteases, respectively). Ca2+, Mg2+ and Ba2+ ions increased its activity, while Al3+, Cu2+, Ni2+ and Zn2+ inhibited it. Additionally, ZnCl2 showed a dose dependent inhibition of the enzyme. Lmr-MP activity was also evaluated upon chromogenic substrates for plasma kallikrein (S-2302), plasmin and streptokinase-activated plasminogen (S-2251) and Factor Xa (S-2222) showing the highest activity on S-2302. The activity in different solutions (5 mM or 50 mM ammonium bicarbonate, pH 7.8; 0.1% trifluoroacetic acid + 50% acetonitrile; phosphate buffer saline, pH 7.4; 50 mM sodium acetate, pH 4.0 or ammonium acetate pH 4.5) was also evaluated and the results showed that its activity was abolished at acidic pHs. Its molecular mass (22,858 Da) was determined by MALDI-TOF and about 90% of its primary structure was verified by high-resolution mass spectrometry using HCD and ETD fragmentations and database search against the sequence of closely related species. It is a novel enzyme which shared high identity with other snake venom metalloproteases (svMPs) belonging to the P-I group.ConclusionThe purification procedure achieved a novel pure highly active metalloprotease from LmrV. This new molecule can help to understand the metalloproteases mechanisms of action, the Lachesis envenoming, as well as to open new perspectives for its use as therapeutic tools.

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“…It should be noted that systemic administration of high PLA2 doses can cause disruptions in the structure of myocardial tissue [ 21 , 94 ] and its functioning, such as bradycardia and atrioventricular block [ 95 , 96 ]. Interestingly, some of the cardiotoxic effects observed in in vivo animal studies are due to disruptions in the composition of the internal medium of the organism [ 97 , 98 ]. PLA2s derived from the venoms of different snakes can differ significantly in their cardiotoxicity; e.g., PLA2s from O. hannah and N. nigricollis cause intracellular structural changes and contracture [ 94 , 96 , 99 ], in contrast to the PLA2 from the venom of N. naja atra that lacks cardiotoxicity [ 99 ].…”

Section: Snake Venoms: Composition and Propertiesmentioning

confidence: 99%

“…Acting on blood vessels, PLA2s usually exert a vasorelaxant effect that is independent of the endothelium and is partially mediated by an increase in cGMP in smooth muscle cells [ 18 , 19 ]. The PLA2 effects can be significantly weakened by suramin [ 100 ] and a phospholipase A2 inhibitor: p -bromophenacyl bromide [ 21 , 97 ]. As in the case of CTs, the PLA2 effects can be blocked by a high concentration of calcium ions, while calcium channel blockers are ineffective [ 19 , 96 ].…”

Section: Snake Venoms: Composition and Propertiesmentioning

confidence: 99%

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Аверин

Utkin

2021

Acta Naturae

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Snake venoms, as complex mixtures of peptides and proteins, affect various vital systems of the organism. One of the main targets of the toxic components from snake venoms is the cardiovascular system. Venom proteins and peptides can act in different ways, exhibiting either cardiotoxic or cardioprotective effects. The principal classes of these compounds are cobra cardiotoxins, phospholipases A2, and natriuretic, as well as bradykinin-potentiating peptides. There is another group of proteins capable of enhancing angiogenesis, which include, e.g., vascular endothelial growth factors possessing hypotensive and cardioprotective activities. Venom proteins and peptides exhibiting cardiotropic and vasoactive effects are promising candidates for the design of new drugs capable of preventing or constricting the development of pathological processes in cardiovascular diseases, which are currently the leading cause of death worldwide. For example, a bradykinin-potentiating peptide from Bothrops jararaca snake venom was the first snake venom compound used to create the widely used antihypertensive drugs captopril and enalapril. In this paper, we review the current state of research on snake venom components affecting the cardiovascular system and analyse the mechanisms of physiological action of these toxins and the prospects for their medical application.

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Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats

Cited by 14 publications

References 66 publications

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

Purification and enzymatic characterization of a novel metalloprotease from Lachesis muta rhombeata snake venom

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

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