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PubMed1999

Identification of bothrojaracin-like proteins in snake venoms from Bothrops species and Lachesis muta.

Bothrojaracin, a 27 kDa protein isolated from Bothrops jararaca venom, forms a non-covalent complex with thrombin, thus blocking its activity. We have previously identified a bothrojaracin-like protein in B. alternatus venom [Castro, H.C., Dutra, D.L.S., Oliveira-Carvalho, A.L., Zingali, R.B., 1998. Bothroalternin, an inhibitor of thrombin from the venom of Bothrops alternatus. Toxicon 36, 1903-1912]. In this report, we have examined snake venoms from six different Bothrops species (B. atrox, B. cotiara, B. jararacussu, B. moojeni and B. neuwiedi), from Lachesis muta and from Crotalus durissus terrificus for the presence of bothrojaracin-like proteins, which we define here as 27 kDa proteins that are immunologically related to bothrojaracin and that inhibit thrombin-induced platelet aggregation. The immunological analysis of these venoms by different techniques indicated the existence of at least one protein recognized by anti-bothrojaracin serum in all venoms tested. Bothrojaracin-like proteins were purified from all crude venoms, except for C. d. terrificus, by a single-step procedure using a thrombin affinity column (PPACK-thrombin-Sepharose). Retained material that inhibits thrombin-induced platelet aggregation was found in a different proportion in each species. Under non-reducing conditions, SDS-PAGE of this material revealed several bands between 20-60 kDa; only those bands corresponding to 27 kDa were recognized by anti-bothrojaracin serum. ELISA confirmed the greater bothrojaracin immunoreactivity of proteins present in B. atrox and B. cotiara as compared to other Bothrops species. Smaller amounts of proteins related to bothrojaracin were found in L. muta venom and were absent from the venom of C. d. terrificus. Our results thus suggest that bothrojaracin-like proteins are widely distributed among Bothrops genera.

Animals↗

PubMed1998

A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on Antivenom Therapy Research (REGATHER).

The therapeutic efficacy and the incidence of early antivenom reactions (EARs) were compared in a clinical trial performed in 79 patients bitten by Bothrops sp. in Urabá, Colombia. Patients were randomized into three groups according to the antivenom administered: A (n = 30, Butantan polyspecific, pepsin-digested Bothrops antivenom); B (n = 27, Butantan polyspecific, whole IgG Bothrops antivenom); and C (n = 22, Colombian commercial, monovalent, whole IgG Bothrops antivenom). The groups were comparable in all clinical and epidemiologic aspects; 33 patients had mild, 22 moderate, and 24 severe envenoming. At the doses used (two, four, and six vials [10 ml/vial] for mild, moderate, and severe envenomings, respectively) there were no differences between the antivenoms in restoring normal hemostatic parameters within 24 hr. The evolution of local envenoming was comparable in the three groups. Serum venom/antivenom kinetics determined by ELISA showed a complete clearance of venom levels 1 hr after treatment in mild/moderate envenomings. In severe cases, venom levels remained detectable up to 24 hr and recurrence of antigenemia was observed in some cases. Antivenom concentrations remained at high levels up to 24 hr of treatment. The incidence of EARs was significantly different in the groups: A (36.7%), B (11.1.%), and C (81.8%). There were no life-threatening anaphylactic reactions. We conclude that the efficacy of the three antivenoms was similar in neutralizing human Bothrops envenomings and that the production of whole IgG antivenoms by caprylic acid fractionation is a good alternative for reducing the incidence of EARs.

Adolescent↗

PubMed1997

[Neutralizing capacity of ++antiophidic sera against the venom of Bothrops moojeni (lance-headed viper)].

In the production of current therapeutic antisera used in Argentina for Bothrops snakebite, the Bothrops moojeni venom is not used as immunogen, since this snake is not considered a serious public health problem. Accidents caused by this species have not been reported in this country even though Bothrops moojeni is not unfrequent in some regions of Misiones. Despite the high degree of immunological cross reactivity found among the Crotalinae venoms and, in this particular case, among the venoms from the Bothrops Genus, there exists a significant intraspecific variation in venom composition, particularly in specimens arising from different geographic regions. In this study, the antivenoms prepared at the Instituto Nacional de Producción de Biológicos A.N.L.I.S. Dr. Carlos G. Malbrán have been tested for their immunochemical cross reactivity and neutralizing ability of enzymatic and toxic activities of venom from Argentinian specimens of Bothrops moojeni from Misiones. Immunological cross-reactivity was tested by double-immunoprecipitation, immunoelectrophoresis, Western-blot and ELISA. Neutralizing ability of antivenoms against proteolytic, indirect hemolytic activity, procoagulant activity, he-morrhagic activity and necrotizing activity. The Lethal Dose 50 was 1.5 mg/kg body weight; this value is located in the range to those obtained with the venom from Brazilian specimens. It was observed that all the antivenoms exhibited a strong immunochemical cross reactivity and that they were able to neutralize in different degree both, enzymatic and toxic activities of B. moojeni venom. From these results, it can be assumed that the antivenom tested could be employed successfully in cases of B. moojeni snakebites.

Animals↗

PubMed1990

Enzyme-linked immunosorbent assay for the detection of Bothrops jararaca venom.

This study reports an enzyme-linked immunosorbent assay for detecting Bothrops jararaca venom in fluids, employing the sandwich method with biotin/avidin amplification. The assay exhibits high accuracy in correlating optical densities with venom concentrations (r = 0.98), high reproducibility, low background and limited cross-reactivity with venom from other snake genera. Nevertheless, it was unable to distinguish among venoms from different bothropic species. Using this method we evaluated the serum kinetics of Bothrops jararaca venom in C57BL/6 mice. High concentrations were found in serum just 15 min after injection (151 +/- 41 ng/ml; mean +/- S.D.), followed by a progressive fall (102 +/- 46, 74 +/- 39 and 50 +/- 22 ng/ml after 1, 3 and 6 hr respectively), being undetectable by 24 hr. Such serum kinetics indicates a pattern of a rapid absorption of venom from the inoculation site, followed by a slow and progressive drop in its serum levels. This ELISA was a reliable tool in the determination of Bothrops jararaca venom levels in mouse serum, and may become useful in other fields of bothropic venom research.

Animals↗

PubMed1991

Neutralization of myotoxic activity of Bothrops venoms by antisera to purified myotoxins and to crude venoms.

A phospholipase myotoxin (MOO-1) and a non-phospholipase myotoxin (JSU-5) were studied for their antigenic cross-reactivity and neutralization by different antisera. Antisera against JSU-5 and MOO-1 reacted equally with both myotoxins in ELISA assays. The specificity of these antisera was also similar, recognizing the same 14,000-18,000 mol. wt components in the venoms of Bothrops jararacussu, Bothrops moojeni, Bothrops neuwiedi and Bothrops pradoi. Using creatine kinase assays, JSU-5 myotoxicity was completely neutralized by B. jararacussu antivenom or anti-JSU-5 antibodies and partially neutralized by B. moojeni antivenom or anti-MOO-1 antibodies. MOO-1 myotoxicity was completely neutralized by antisera against JSU-5 and MOO-1 and B. jararacussu antivenom, and only partially neutralized by B. moojeni antivenom. B. jararacussu venom induced high titres of antibodies against purified myotoxins. This antiserum completely inhibited the myotoxicity of the homologous venom and significantly reduced the myotoxicity of the remaining myotoxin-containing venoms. It is suggested that B. jararacussu venom is a good immunogen to induce antibodies against myotoxins present in the venoms of the different species of Bothrops.

Animals↗

PubMed1995

Phospholipase A2 myotoxins from Bothrops snake venoms.

Several myotoxins have been isolated from Bothrops snake venoms during the last 10 years. All of them are group II basic phospholipases A2, although some lack enzymatic activity (i.e. Lys-49 variants). These myotoxins appear as an antigenically related family of proteins occurring in many, but not all, Bothrops venoms, bearing a close structural and antigenic relationship to toxins found in other crotalid venoms of the genera Agkistrodon and Trimeresurus. Myotoxins are quantitatively important venom components in some Bothrops species. Intramuscular injection of Bothrops myotoxins leads to a rapid series of drastic degenerative events, probably initiated at the plasma membrane level, which culminate in a selective skeletal muscle necrosis. This in vivo specificity contrasts with the ability of myotoxins to lyse many types of cells in culture. Muscle damage, as well as cytolysis and liposome disruption, occur in conditions where phospholipase A2 activity is inhibited, although enzymatic activity might enhance myotoxin actions. A membrane receptor for Bothrops myotoxins has not been identified yet. A working hypothesis on the mechanism of action is proposed. Current evidence suggests that these toxins interact with biological membranes via a molecular region distinct from their known catalytic site. The active region is likely to be formed by a combination of basic and hydrophobic amino acid residues near the C-terminus of the protein, which allow electrostatic interaction and bilayer penetration. These events may lead to membrane destabilization and loss of selective permeability to ions such as calcium, both of which appear to be important mediators in the process of muscle necrosis.

Amino Acid Sequence↗

PubMed2005

Neutralization of four Peruvian Bothrops sp. snake venoms by polyvalent antivenoms produced in Perú and Costa Rica: preclinical assessment.

Envenomations after bites inflicted by snakes of the genus Bothrops constitute a public health hazard in Perú, and the intravenous administration of equine-derived antivenoms represents the only scientifically validated treatment. This study presents a preclinical assessment of the efficacy of two whole IgG antivenoms, prepared in Perú and Costa Rica, to neutralize the most relevant toxic effects induced by the venoms of Bothrops atrox, B. brazili, B. barnetti and B. pictus from Perú. Peruvian antivenom is produced by immunizing horses with Bothrops sp. venoms from this country, whereas the production of Costa Rican antivenom involves immunization with venoms from Central American snakes. The neutralization of lethal, hemorrhagic, edema-forming, myotoxic, coagulant and defibrinating activities was evaluated in assays involving incubation of venom and antivenom prior to testing. Both antivenoms were effective in the neutralization of these effects, with quantitative variations in the values of effective dose 50% depending on the effects being studied. Peruvian antivenom was more effective in the neutralization of lethality induced by B. atrox and B. barnetti venoms. However, Peruvian antivenom failed to neutralize coagulant activity of B. barnetti venom and edema-forming activity of B. brazili venom, whereas neutralization was achieved by Costa Rican antivenom. It is concluded that an extensive immunological cross-reactivity exists between Bothrops sp. venoms from Perú and Costa Rica, and that both antivenoms are effective in the neutralization of these four venoms in a rodent model of envenoming.

Animals↗

PubMed2005

Biological and immunological properties of the venom of Bothrops alcatraz, an endemic species of pitviper from Brazil.

Bothrops alcatraz is a new pitviper species derived from the Bothrops jararaca group, whose natural habitat is situated in Alcatrazes Archipelago, a group of marine islands near São Paulo State coast in Brazil. Herein, the biological and biochemical properties of venoms of four adult specimens of B. alcatraz were examined comparatively to a reference pool of Bothrops jararaca venom. Both venoms showed similar activities and electrophoretic patterns, but B. alcatraz venom showed three protein bands of molecular masses of 97, 80 and 38 kDa that were not present in B. jararaca reference venom. The i.p. median lethal dose of B. alcatraz venom ranged from 5.1 to 6.6 mg/kg, while it was 1.5 mg/kg for B. jararaca venom. The minimum hemorrhagic dose of B. jararaca venom was 0.63, whereas 2.28 mug/mouse for B. alcatraz venom. In contrast, B. alcatraz venom was more potent in regard to procoagulant and proteolytic activities. These differences were supported by western blotting and neutralization tests, employing commercial bothropic antivenom, which showed that hemorrhagic and lethal activities of B. alcatraz venom were less effectively inhibited than B. jararaca venom. Such results evidence that B. alcatraz shows quantitative and qualitative differences in venom composition in comparison with its B. jararaca relatives, which might represent an optimization of venom towards a specialized diet.

Animals↗

PubMed2005

Purification and characterization of a hemorrhagic metalloproteinase from Bothrops lanceolatus (Fer-de-lance) snake venom.

Bothrops snake venoms contain metalloproteinases that contribute to the local effects seen after envenoming. In this work, a hemorrhagic metalloproteinase (BlaH1) was purified from the venom of the snake Bothrops lanceolatus by a combination of gel filtration, affinity (metal chelating) and hydrophobic interaction chromatographies. The hemorrhagin was homogeneous by SDS-PAGE and had a molecular mass of 28 kDa that was unaltered by treatment with beta-mercaptoethanol. BlaH1 gave a single band in immunoelectrophoresis and immunoblotting using commercial bothropic antivenom. BlaH1 had hemorrhagic, caseinolytic, fibrinogenolytic, collagenolytic and elastinolytic activities, but no phospholipase A(2) activity. The hemorrhagic and caseinolytic activities were inhibited by EDTA, indicating that they were metal ion-dependent. In contrast, aprotinin, benzamidine and PMSF did not affect these activities. The caseinolytic activity of BlaH1 had a pH optimum of 8.0 and was stable in solution at up to 40 degrees C; activity was completely lost at > or =70 degrees C. The hemorrhagic activity was neutralized by commercial bothropic antivenom. These properties suggest that this new hemorrhagin belongs to class P-I snake venom metalloproteinases.

Animals↗

PubMed2003

Structural and functional analysis of BmjMIP, a phospholipase A2 myotoxin inhibitor protein from Bothrops moojeni snake plasma.

A protein, which neutralizes the enzymatic, toxic, and pharmacological activities of various basic and acidic phospholipases A(2) from the venoms of Bothrops moojeni, Bothrops pirajai, and Bothrops jararacussu, was isolated from B. moojeni snake plasma by affinity chromatography using immobilized myotoxins on Sepharose gel. Biochemical characterization of this myotoxin inhibitor protein (BmjMIP) showed it to be an oligomeric glycoprotein with a M(r) of 23,000-25,000 for the monomeric subunit. BmjMIP was stable in the pH range from 4.0 to 12.0, between 4 and 80 degrees C, even after deglycosylation. The role of the carbohydrate moiety was investigated and found not to affect the in vitro function of the inhibitor. The corresponding 500bp cDNA obtained by RT-PCR from the liver of the snake encodes a mature protein of 166 amino acid residues including a 19 amino acid signal peptide. The primary structure of BmjMIP showed a high similarity with other snake phospholipase A(2) inhibitors (PLIs) in which the carbohydrate recognition domain (CRD) and the glycosylation site (Asn103) are conserved. Circular dichroism spectroscopy indicated that no significant alterations in the secondary structure of either the BmjMIP or the target protein occur upon their interaction. BmjMIP has a wide range of inhibitory properties against basic and acidic PLA(2)s from Bothrops venoms (anti-enzymatic, anti-myotoxic, anti-edema inducing, anti-cytotoxic, anti-bactericidal, and anti-lethal). However, the inhibitor showed a reduced ability to neutralize the biological activities of crotoxin B (CB), the PLA(2) homologue associated with crotapotin in Crotalus durissus terrificus snake venom. Finally, the purified PLA(2) inhibitor was shown to protect in vivo against the toxic and pharmacological effects of a homologous PLA(2) enzyme, suggesting that PLIs or a corresponding derived peptide may prove useful in the treatment of snakebite victims or, more importantly, in the treatment of the many human diseases in which these enzymes have been implicated.

Amino Acid Sequence↗

PubMed2000

Neutralizing potency of horse antibothropic Brazilian antivenom against Bothrops snake venoms from the Amazonian rain forest.

Neutralization of lethal toxicity (50% effective dose; ED(50)), hemorrhagic (minimum hemorrhagic dose; MHD) and hemolytic activity (PLA(2)) and levels of antibodies, measured by enzyme-linked immunosorbent assay (ELISA), were investigated to test the potency of horse antibothropic serum (ABS) against Bothrops venoms from the Amazonian rain forest. ABS neutralized the lethal activity with a potency (mg of venom neutralized per 1 ml of antivenom) of 5.5, 3.7, 1.6, 1.3 and 6.5, respectively, for B. jararaca (reference venom for assessing the ABS potency in Brazil), B. atrox, B. brazili, B. bilineatus smaragdinus and B. taeniatus venoms. The volume of antivenom (microl) that neutralized one MHD of B. jararaca, B. atrox, B. brazili, B. bilineatus smaragdinus and B. taeniatus venoms was 5, 7.71, 7.76, 8.3 and 5, respectively. ABS neutralized the PLA(2) activity with a potency of 6.2, 3.2, 1.4, 2.6 and 5 respectively, for B. jararaca, B. atrox, B. brazili, B. bilineatus smaragdinus and B. taeniatus venoms. ELISA reactivity of ABS against the separate venoms was found to be quite variable. The reactivity against B. jararaca venom was higher than against other Bothrops venoms. In conclusion, the assays described here suggest that Brazilian Bothrops polyspecific antivenom is not very efficient in neutralizing the effects of venom from some Amazonian Bothrops species.

Animals↗

PubMed1997

An enzyme-linked immunosorbent assay (ELISA) that discriminates between the venoms of Brazilian Bothrops species and Crotalus durissus.

Enzyme-linked immunosorbent assays (ELISAs) were developed to detect specific antigens from Bothrops sp. and Crotalus durissus snake venoms in Brazil. Cross-reactive immunoglobulins from hyperimmune horse anti-Bothrops and anti-Crotalus sera were removed by immunoaffinity chromatography. Specific IgGs for Bothrops sp. and C. durissus venom antigens were prepared and used to set up a sandwich-type ELISA. The specificity of the assay was demonstrated by its capacity to identify correctly the circulating antigens in mice experimentally inoculated with both venoms. Measurable absorbance signals were obtained with 5 ng of venom per assay. The ELISA was also used to identify circulating antigens in the sera of humans bitten by Bothrops sp. and C. durissus. These ELISAs could be valuable for clinicians and epidemiologists if they prove to have both the high sensitivity and specificity required for such tests.

Animals↗

PubMed1998

Bothrops sp. snake venoms: comparison of some biochemical and physicochemical properties and interference in platelet functions.

Procoagulant, proteolytic, phospholipase and platelet pro-aggregating and inhibiting activities were screened for pooled venoms of seven Bothrops species as well as Crotalus durissus terrificus and Lachesis muta snakes typical of the Brazilian territory. As reported by other authors, we also found that examination of the electrophoretic and gel filtration patterns of Bothrops snakes venoms could not be used for identification of the species of a given venom because of the lack of marked interspecific differences within the same genus. Our data indicated that B. cotiara, B. alternatus and B. atrox possess no platelet pro-aggregating activity, low inhibitory effect on platelet aggregation and very low or intermediate levels for the other activities. B. moojeni, B. neuwiedi and B. jararacussu whose venoms possess high procoagulant, platelet pro-aggregating and phospholipase activities are low in both proteolytic and platelet inhibitory activities. B. jararaca venom showed the highest inhibitory effect on platelet aggregation and very low platelet pro-aggregating activity. Compared with the Bothrops venoms studied, L. muta venom showed that highest proteolytic activity while C. d. terrificus venom presented remarkable high platelet pro-aggregating and phospholipase activities. In all venoms, proteolytic activity could be completely inhibited by EDTA (2 mM) alone. In contrast, the presence of phenylmethylsulfonyl fluoride (5 mM) inhibited partially the caseinolytic activity of all venoms, except that L. muta venom, which was almost completely blocked by this reagent. Altogether, these data confirm the presence of high levels of metalloproteinases in the venoms of Crotalinae snakes. Most of these enzymes are dependent of the availability of Ca2+, being much less the same concerning the presence of serine residues in their active sites. The data indicated that the presence and levels of procoagulant, azocaseinolytic and phospholipase A2 activities alone could not differentiated the species of the Bothrops venoms studied, particularly in the cases of B. jararaca, B. moojeni and B. atrox. However, the platelet inhibiting property of low doses of B. jararaca venom can be useful to differentiate it from B. moojeni venom. In the same way, the platelet pro-aggregating activity of high doses of B. jararaca venom may be used to distinguish it from B. atrox crude venom, otherwise very similar but incapable to activate platelets. In conclusion, our comparative screening of biological properties has indicated that platelet studies may serve as a tool to distinguish among venoms that otherwise behave biochemically in a very similar way. Although promising, the general applicability of platelet activation studies by snake venoms for classification or taxanomical purposes has yet to be extended to other family of snakes to be proven useful.

Animals↗

PubMed1998

Geographic variations in the composition of myotoxins from Bothrops neuwiedi snake venoms: biochemical characterization and biological activity.

(1) Venom pools from Bothrops neuwiedi (Bn) and from two subspecies, namely Bothrops neuwiedi pauloensis (Bnp) and Bothrops neuwiedi urutu (Bnu), collected in the States of São Paulo (SP) and Minas Gerais (MG), Brazil, were electrophoretically examined. Basic toxins with different isoelectric points were identified in the venom collected in São Paulo (BnSP). These toxins were absent in the corresponding pools from Minas Gerais (BnMG, BnpMG and BnuMG). (2) BnSP, but not BnMG, BnpMG or BnuMG, showed two myotoxins (pI approximately equal to 8.6 and 8.8, respectively) which were isolated by ion-exchange chromatography on CM-Sepharose. (3) From BnMG, three myotoxic isoforms (pI approximately equal to 8.2 and M(r) = 13,600) were isolated by chromatography on CM-Sepharose followed by reversed-phase high-performance liquid chromatography. (4) The chemical and biological characterization of these toxins showed a high similarity with the Lys-49 myotoxins from other bothropic venoms. (5) Doses up to 5 LD50 (i.p.) of p-bromophenacyl bromide alkylated BnSP-7 caused a total loss of lethality in 18-22-g mice, thus indicating that the LD50 was increased by greater than 5-fold. At this dose myotoxicity was also not detectable, but the edematogenic activity on the rat paw apparently did not change.

Alkylation↗

PubMed2004

Cloning and identification of a complete cDNA coding for a bactericidal and antitumoral acidic phospholipase A2 from Bothrops jararacussu venom.

In order to better understand the function of acidic phospholipases A2 (PLA2s) from snake venoms, expressed sequence tags (ESTs) that code for acidic PLA2s were isolated from a cDNA library prepared from the poly(A)+ RNA of venomous glands of Bothrops jararacussu. The complete nucleotide sequence (366 bp), named BOJU-III, encodes the BthA-I-PLA2 precursor, which includes a signal peptide and the mature protein with 16 and 122 amino acid residues, respectively. Multiple comparison of both the nucleotide and respective deduced amino acid sequence with EST and protein sequences from databases revealed that the full-length cDNA identified (BOJU III--AY145836) is related to an acidic PLA2 sharing similarity, within the range 55-81%, with acidic phospholipases from snake venoms. Moreover, phylogenetic analysis of amino acid sequences of acidic PLA2s from several pit viper genera showed close evolutionary relationships among acidic PLA2s from Bothrops, Crotalus, and Trimeresurus. The molecular modeling showed structural similarity with other dimeric class II PLA2s from snake venoms. The native protein BthA-I-PLA2, a nontoxic acidic PLA2 directly isolated from Bothrops jararacussu snake venom, was purified and submitted to various bioassays. BthA-I-PLA2 displayed high catalytic activity and induced Ca2+-dependent liposome disruption. Edema induced by this PLA2 was inhibited by indomethacin and dexamethasone, thus suggesting involvement of the cyclo-oxygenase pathway. BthA-I-PLA2 showed anticoagulant activity upon human plasma and inhibited phospholipid-dependent platelet aggregation induced by collagen or ADP. In addition, it displayed bactericidal activity against Escherichia coli and Staphylococcus aureus and antitumoral effect upon breast adrenocarcinoma as well as upon human leukemia T and Erlich ascitic tumor. Following chemical modification with p-bromophenacyl bromide, total loss of the enzymatic and pharmacological activities were observed. This is the first report on the isolation and identification of a cDNA encoding a complete acidic PLA2 from Bothrops venom, exhibiting bactericidal and antitumoral effects.

Amino Acid Sequence↗

PubMed2002

Multiple cerebral infarctions following a snakebite by Bothrops caribbaeus.

Bothrops caribbaeus, a species of the Bothrops complex, is found only in the island of Saint Lucia, West Indies. Snakebite from this pitviper is very rare. We report the case of a healthy 32-year-old Saint Lucian man who developed multiple cerebral infarctions following envenoming by this snake. This patient developed signs and symptoms very similar to those observed in patients envenomed by Bothrops lanceolatus, a snake found only in Martinique, the neighbor island of Saint Lucia. This clinical presentation differs dramatically from coagulopathies and systemic bleeding observed with the Central and South American bothropic envenomings. The exact mechanism of this thrombogenic phenomenon, leading to a unique envenoming syndrome, remains unknown.

Adult↗

PubMed1991

The effect of myotoxins isolated from Bothrops snake venoms on multilamellar liposomes: relationship to phospholipase A2, anticoagulant and myotoxic activities.

The effect of four myotoxins isolated from Bothrops snake venoms on the release of peroxidase trapped in large multilamellar liposomes was studied and correlated to their phospholipase A2, myotoxic and anticoagulant activities. The four myotoxins affected negatively-charged liposomes in a dose-dependent way, having no effect on positively-charged liposomes. Conditions that inhibited phospholipase A2 activity, i.e., substitution of calcium by EDTA, reduced liposome-disrupting activity of Bothrops asper myotoxin I and Bothrops atrox myotoxin, both of which have high phospholipase A2 activity, but did not affect the action of B. asper myotoxin II and Bothrops moojeni myotoxin II, which have extremely low phospholipase A2 activity. However, all myotoxins disrupted to some extent negatively-charged liposomes under conditions where phospholipase A2 activity was abolished. Since these toxins behave as amphiphilic proteins in charge-shift electrophoresis, it is suggested that membrane-disorganization is at least partially due to a non-enzymatic penetration and alteration of bilayers. There was no strict correlation between liposome-disrupting activity and myotoxicity in vivo. Thus, although both effects probably depend on the toxins' ability to disturb membranes, it is likely that variation in complexity between skeletal muscle plasma membrane and liposome bilayers are the basis for this difference. The anticoagulant effect seems to depend on the ability of the toxins to enzymatically degrade phospholipids, since only B. asper myotoxin I and B. atrox myotoxin prolonged the plasma recalcification time.

Animals↗

PubMed1985

The anticoagulant effect of Bothrops castelnaudi snake venom (Castelnaud's pit viper).

An inhibitory effect of Bothrops castelnaudi venom was observed on the following systems: prothrombin time, activated partial thromboplastin time, thrombin time, thromboplastin generation time, activation of factor X by Russell's viper venom and Russell's viper venom activated factor X (factor Xa). This effect did not require previous incubation and was prevented by the addition of Bothrops-antivenom. The prolonged activated partial thromboplastin time was not shortened by increased phospholipid concentration (0.5-10 mg/ml), suggesting that the inhibitory effect is not due to an anti-phospholipid activity. No significant fibrinogenolytic activity was detected upon incubation of human fibrinogen with the venom, since physiological levels of thrombin-clottable material were still present. Compared to Bothrops jararaca venom, the proteolytic activity on casein and on azocoll was very low. Thrombin-induced clots of human plasma and fibrinogen were not lysed by the venom within 24 hr. The results indicate that the anticoagulant effect of Bothrops castelnaudi venom is exerted at least at two levels of the blood coagulation mechanism: (1) before prothrombin activation, by inhibiting factor X-activation and factor Xa activity; (2) by direct action on thrombin.

Animals↗