hemorrhagic activity
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2022 ◽  
Vol 12 ◽  
Author(s):  
Pamella G. Gutierres ◽  
Diego R. Pereira ◽  
Nataly L. Vieira ◽  
Lilian F. Arantes ◽  
Nelson J. Silva ◽  
...  

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.


Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 803
Author(s):  
Bianca C. Zychar ◽  
Patrícia B. Clissa ◽  
Eneas Carvalho ◽  
Adilson S. Alves ◽  
Cristiani Baldo ◽  
...  

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from B. jararaca venom and BnP-1—a weakly hemorrhagic P1 SVMP from B. neuwiedi venom. Toxins (0.5 µg) or PBS (100 µL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.


Author(s):  
Achala Bhat ◽  
K. S. Rajesh ◽  
Reshma Raghavan

Cassia alata, commonly known as candle bush, ringworm bush is an extensively distributed plant of the family Leguminosea. It is an annual and occasionally biannual herb, flowering in the sunshine and humid areas, with an average height of 1 to 4m. Biological activity in plants has been claimed to be effective as antidiabetic, antimicrobial, antioxidant, anti-inflammatory, anti-allergic, antimicrobial, analgesic, anti-ulcer, antiviral, antidepressants, hepatoprotective, antimalarial, anthelmintic, cardiovascular, and anesthetic properties. The ethanolic extract of plant was subjected first time for neutralization of snake venom activity. Primary phytochemical screening shows the existence of alkaloid, steroids, phenols, flavonoids, and triterpenoids. Ethanolic extract of Cassia alata plants was tested for antivenom activity against Daboia russelii venom. Various dose levels of leaf extract 200 and 400mg/kg showed significant neutralization of hemorrhagic activity, and at 400mg/kg leaf extract showed significant necrotizing activity in rats.


2021 ◽  
Vol 41 (3) ◽  
pp. 234-240
Author(s):  
J.I Achika ◽  
R.G Ayo ◽  
A.O Oyewale ◽  
J.D Habila ◽  
P.Y Ofemile

Bulchhozia coriacea (Capparaceae) seeds are used in managing snake bite in Western Nigeria were investigated against Naja nigricollis (Spitting cobra) venom-induced hemolytic, hemorrhagic and fibrinolytic effects. This study was aimed at determining the antihaemolytic, antihaemorrhagic as well as antifibrinolytic effects of B. coriacea on N. nigricollis crude venom. Microwave-assisted extraction with hexane, chloroform, ethyl acetate, and methanol was carried out. Naja nigricollis venom-induced erythrocyte lysis (100 %) was significantly reduced to 18% by the chloroform fraction at 0.625 mg/mL. At the concentration of 0.625 mg/mL, the hexane, chloroform, ethyl acetate and methanol fractions administered in combination with the venom reduced percentage hemorrhagic activity to 23%, 17%, 49%, and 87%, respectively. In conclusion, Bulchhozia coriacea seed fractions exhibited significant antihaemolytic, antihaemorrhagic and antifibrinolytic activities against N. nigricollis crude venom and may beneficial as a pre-treatment the while victim is transferred to a healthcare facility to receive the definite treatment to ensure speedy recovery. Key words: Antihaemolytic, antihaemorrhagic, fibrinolytic, venom, Bulchhozia coriacea


2021 ◽  
pp. e00742
Author(s):  
S.O. Adeyemi ◽  
Rotimi Larayetan ◽  
Abayomi Ajayi ◽  
A.D. Onoja ◽  
Abdulrazaq Yahaya ◽  
...  

Author(s):  
B. I. Baggai ◽  
P. O. Yusuf ◽  
F. T. Alloh

Envenomation is a serious public health and occupational hazard in tropical and subtropical countries. Antivenom serum treatment has been related to extreme hypersensitivity, high cost, and inaccessibility. Consequently, therapeutic plants have been investigated to give an alternative treatment. The aim of this study was to evaluate the ability of the methanolic extract and fractions of Tamarindus indica seeds to neutralize the hemolytic, anticoagulant and hemorrhagic activities of Bitis arietans venom. The powdered form of Tamarindus indica seed was extracted using methanol. The methanol extract was further fractionated using butanol solvent. The aqueous fraction of the methanolic extract inhibited hemolysis caused by crude venom by 95.5%, while methanolic extract significantly reduced the anticoagulant time of crude venom to 10.2%. The in vivo hemorrhagic activity of the crude venom of Bitis arietans was neutralized by both the crude methanolic extract and the subsequent two fractions of Tamarindus indica seed. However, the crude methanolic extract was found to be the most active by reducing the hemorrhage diameter caused by crude venom to 39%. The findings of this present research work demonstrated a very good antivenom properties of the seeds of Tamarindus indica, which suggests that it could be a potential source of effective, and safe compounds with inhibitory activities against Bitis arietans envenomation.


Toxicon ◽  
2020 ◽  
Vol 177 ◽  
pp. S55
Author(s):  
Erika Camacho ◽  
Alexandra Rucavado ◽  
Teresa Escalante ◽  
José María Gutiérrez ◽  
Kim Remans

2020 ◽  
Vol 73 (4) ◽  
pp. 277
Author(s):  
Narumi Aoki-Shioi ◽  
Cho Yeow Koh ◽  
R. Manjunatha Kini

Snakebites are a hazard in the tropical world. Although antivenom therapy is effective, it is beset with inherent drawbacks. A better understanding of the major components of snake venoms and their neutralisation will help in improving snakebite treatment. Snake venom metalloproteinases (SVMPs) are responsible for severe haemorrhage, the inhibition of coagulation and platelet aggregation, observed in the victims of snakebite envenoming. Inhibitors from various sources including medicinal plants, animal venoms, and sera are sought to block the pharmacological functions of SVMPs. In this review, we describe the interaction of natural inhibitors with SVMPs. To understand their inhibitory mechanisms, we focussed on the complex structures of these inhibitors and SVMPs. There are three distinct classes of inhibitors; namely, chelators, competitive inhibitors, and non-competitive inhibitors. A small number of inhibitors show their anti-hemorrhagic activity in invivo animal models in treatment mode, but most studies evaluate either invitro neutralisation of enzymatic activity or invivo effects in pre-incubation protocols. We propose the distinct strategies and limitations to design either broad-spectrum or highly selective SVMP inhibitors. The goal of designing broad-spectrum inhibitors against SVMPs capable of effective treatment of snakebites without toxicity has been elusive, probably because of the narrow molecular footprint of inhibitors against a large number of SVMPs with distinct molecular surfaces. Our ability to design highly selective inhibitors is limited by the lack of information of interactions between selective inhibitors and SVMPs. Comparisons of structures of hemorrhagic and non-hemorrhagic SVMPs revealed different distributions of electric charge on the surface of SVMPs, which may be exploited to design specific inhibitors. The specific inhibitors may also be useful to identify target molecules of the SVMPs and help to understand their mechanism of action.


2019 ◽  
Vol 67 (4) ◽  
Author(s):  
Silvana Marcussi ◽  
Lucilene Fernandes Silva ◽  
Mariana Aparecida Braga ◽  
Mariana Araújo Espósito ◽  
Pedro Henrique Souza Cesar

Snake venom are widely used as laboratory tools for studies of physiological, pharmacological and toxicological mechanisms. Venoms used here are rich sources of several classes of proteases that act on factors of the coagulation cascade, fibrinogenolysis and fibrinolysis, altering the hemostatic processes, and phospholipases A2 which are involved mainly in inflammatory and clotting processes since they act hydrolyzing membrane phospholipids and may result in the release of arachidonic acid whose structure is a precursor of eicosanoids by cyclooxygenase and lipoxygenase pathways. Natural products such as essential oils are made up of active ingredients with wide application in the food, pharmaceutical and cosmetic industries. Thus, in this study evaluate the essential oils from Mentha viridis and Mentha pulegium on coagulation, fibrinogenolysis and degradation of azocasein, induced by Bothrops sp and Lachesis muta muta venoms. These oils were achieved by hydrodistillation and presented, respectively, as the main constituents linalool (40.70%), carvone (13.52%) and α-terpinene (8.56%); pulegone (50.01%), menthol (31.90%) and menthone (16.56%). The essential oils were previously incubated with Bothrops alternatus venom, for two different times, plasma was added and timing. The M. pulegium and M. viridis oils in the volume of 0.30 μL (10 min of incubation) presented greater anticlotting potential. Meanwhile, 0.15 μL the M. pulegium oil presented proclotting activity. In 20 min of incubation, both oils presented anticlotting activity with 0.15 and 0.30 μL. At azocaseinolytic assay the oil from M. pulegium reduced the activity for all evaluated venoms. The highest inhibitions were 34.33% and 39.99% for 0.6 and 1.2 μL of oil, respectively; on activity induced by B. jararacussu, M. viridis with 0.6 and 1.2 μL reduced the activity in 40.93% and 57.72%, respectively. On B. moojeni, the same volumes were responsible for inhibitions of 74.67% and 47.4%, respectively. The fibrinogenolysis induced by B. moojeni venom was totally inhibited by both oils in the evaluated proportions. The results show the presence in oils of protease inhibitors, considering metalloproteases (mainly with thrombin-like and hemorrhagic activity) and serineproteases (actuating on clotting factors), as well as phospholipase A2­ inhibitors (involved in inflammation and clotting processes) of wide application in medical and biotechnology areas.  


2019 ◽  
Vol 47 ◽  
Author(s):  
Raissa Lopes Lima ◽  
Paulo Victor Braga ◽  
Nathálye Fernandes Pelegrini ◽  
Arlena Do Bom Parto Ferreira de Almeida ◽  
Adriane Jorge Mendonça ◽  
...  

Background: Snakebites occur frequently among humans and animals. In Brazil, about 23,000 cases of snakebite involving humans were recorded in 2016, 11% of them caused by venomous snakes. In the region of Cuiabá, capital of Mato Grosso, the highest occurrence is of snakes of the genus Bothrops (81%), followed by Crotalus (4%). Bothrops venom has proteolytic, coagulant and hemorrhagic effects, whereas Crotalus venom is neurotoxic, myotoxic and nephrotoxic. This paper reports on three cases of Bothrops snakebites in dogs treated at the Veterinary Hospital of the Federal University of Mato Grosso in 2017.Cases: Three dogs were treated showing clinical signs of snakebite, possibly by Bothrops, since their owners reported that these are the snakes most frequently found where they live. This information is consistent with the known geographic distribution of snakes of the genus Bothrops in the state of Mato Grosso, Brazil. In the first report (Case 11), the patient was bitten on two different occasions in a five-month interval, and died presumably due to anaphylactic shock caused by the venom injected by a second snakebite (Case 12). In both episodes, the animal presented a swollen face and neck, dyspnea and eye bleeding, and these signs were more severe in the second episode. Case 2 was a dog with severe neck and chest swelling and pain. The owner of this dog reported that he had taken his dog for a walk in the countryside, along with the dog of Case 1, and had returned home with both dogs about three hours before the consultation. Case 3 was a Rottweiler living at a small family farm located 67 km from Cuiabá. The animal presented with slight swelling and pain in the left forelimb, and puncture wounds on the lower limb. Neutrophilic leukocytosis was observed in cases 1 and 3.  In addition, Case 12 (the second episode of Case 1) presented with thrombocytopenia and increased prothrombin time and activated partial thromboplastin time. The dog of Case 2 presented no hematological or biochemical alteration. All the dogs received antivenom serum and supportive care.Discussion: Based on the clinical signs of local swelling with bleeding and absence of neurological signs, the snakebites were attributed to the genus Bothrops. In Case 12, blood clotting tests showed non-coagulation. The greater severity of Case 1, which culminated in death, was attributed to anaphylaxis due to prior exposure or the larger amount of venom than that injected in Case 2, since the two injuries were inflicted in the same environment on the same day, probably by the same snake. Neutrophilic leukocytosis may be indicative of an inflammatory reaction, while thrombocytopenia and clotting changes are associated with the hemorrhagic activity of Bothrops venom. Death by snakebite is directly linked to the amount of venom injected, the envenomation site, and the time between the bite and the beginning of treatment. This explains the moderate signs presented by Cases 2 and 3, whose injuries were inflicted on the neck and forelimb, unlike the dog of Case 1, which was bitten on the head on two occasions. It was concluded that Bothrops venom causes systemic and local alterations characterized by pain, swelling, necrosis and bleeding. Early access to antivenom treatment is essential to neutralize clinical signs and prevent worsening of systemic poisoning. The determining factor in snakebite deaths is the amount of injected venom and the time elapsed between the injury and the beginning of treatment.


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