Lonomia obliqua venomous secretion induces human platelet adhesion and aggregation.
ABSTRACT The caterpillar Lonomia obliqua is a venomous animal that causes numerous accidents, especially in southern Brazil, where it is considered a public health problem. The clinical manifestations include several haemostatic disturbances that lead to a hemorrhagic syndrome. Considering that platelets play a central role in hemostasis, in this work we investigate the effects of L. obliqua venomous secretion upon blood platelets responses in vitro. Results obtained shows that L. obliqua venom directly induces aggregation and ATP secretion in human washed platelets in a dose-dependent manner. Electron microscopy studies clearly showed that the venomous bristle extract was also able to produce direct platelets shape change and adhesion as well as activation and formation of platelet aggregates. Differently from other enzyme inhibitors, the venom-induced platelet aggregation was significatively inhibited by p-bromophenacyl bromide, a specific inhibitor of phospholipases A2. Additional experiments with different pharmacological antagonists indicate that the aggregation response triggered by the venom active components occurs through a calcium-dependent mechanism involving arachidonic acid metabolite(s) of the cyclooxygenase pathway and activation of phosphodiesterase 3A, an enzyme that leads to the consumption of intracellular cAMP content. It was additionally found that L. obliqua-induced platelet aggregation was independent of ADP release. Altogether, these findings are in line with the need for a better understanding of the complex hemorrhagic syndrome resulting from the envenomation caused by L. obliqua caterpillars, and can also give new insights into the management of its clinical profile.
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ABSTRACT: Lonomia obliqua envenomation is characterized by intense local inflammatory reaction, which, dependent on the severity of the case, is followed by severe clinical manifestations related to hemorrhagic disorders that can lead to fatal outcome. These effects were imputed to several toxins present in L. obliqua venom, which are responsible for procoagulant, anticoagulant as well as antithrombotic activities, being also able to interfere with vascular cells functions. In this work, the intravital microscopy analysis show that after administration of low doses of L. obliqua venom (1-3 μg/ml) on hamster cheek pouch, there was no alterations neither on arterioles or venules caliber nor in the vascular permeability up to 30 min. However, after 10 min in contact with venom occurred a clear activation in the vascular bed, characterized by an increase in leukocyte rolling and adhesion on endothelium of hamster cheek pouch venules. A confocal analysis of vascular beds, confirmed these results showing an increase in endothelial E-selectin and VCAM-1 expression. The effects of L. obliqua venom on human endothelial cell (EC) in vitro were also investigated. The treatment of EC with venom (1-3 μg/ml) did not affect cell viability. However, at concentrations as low as 3 μg/ml of L. obliqua venom modifies actin cytoskeleton dynamics, and increases focal adhesion contacts, inducing stress fiber formation, focal adhesion kinase (FAK) phosphorylation and its subsequent association to actin. These effects are followed by the activation of NF-κB pathway, a critical signaling in several events associated to vascular inflammation. Accordingly, L. obliqua venom leads to a significant increase in COX-2, NOS-2, HO-1, MMP-2 and MMP-9 expression. Taken together the data show that, even at low concentrations, L. obliqua venom can activate endothelial cells, which assume a pro-inflammatory profile, contributing for local effects and probably also for systemic disturbances due to its ability to modulate the properties of the vascular system.Toxicon 07/2012; 60(1):50-60. · 2.58 Impact Factor
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ABSTRACT: The clinical manifestations of Lonomia obliqua caterpillar envenomation are systemic hemorrhage and acute kidney injury. In an effort to better understand the physiopathological mechanisms of envenomation, a rat model was established to study systemic tissue damage during L. obliqua envenomation. An array of acute venom effects was characterized, including biochemical, hematological, histopathological, myotoxic and genotoxic alterations. Rapid increases in serum alanine and aspartate transaminases, γ-glutamyl transferase, lactate dehydrogenase, hemoglobin, bilirubin, creatinine, urea and uric acid were observed, indicating that intravascular hemolysis and liver and kidney damage had occurred. Treatment with a specific antivenom (antilonomic serum) for up to 2 h post-venom injection neutralized the biochemical alterations. However, treatment after 6 h post-venom injection failed to normalize all biochemical parameters, despite its efficacy in reversing coagulation dysfunction. The hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. The histopathological alterations were mainly related to hemorrhage and inflammation in the subcutaneous tissue, lung, heart and kidneys. Signs of congestion and hemosiderosis were evident in the spleen, and hemoglobin and/or myoglobin casts were also detected in the renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with the myocardial necrosis observed in vivo and confirmed the myotoxicity detected in vitro in isolated extensor digitorum longus muscles. Significant DNA damage was observed in the kidneys, heart, lung, liver and lymphocytes. The majority of the DNA lesions in the kidney were due to oxidative damage. The results presented here will aid in understanding the pathology underlying Lonomia's envenomation.Toxicon 08/2013; · 2.58 Impact Factor
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ABSTRACT: Erucism is a skin reaction to envenomation from certain poisonous caterpillar bristles. In Brazil, most reports of erucism provoked by Lonomia caterpillars are from the southern region. Most manifestations of erucism are local and include burning pain, itching, local hyperthermia and, rarely, blisters (benign symptoms with spontaneous regression in a few hours). General symptoms such as nausea and vomiting, headache, fever, myalgia, abdominal pain and conjunctivitis may also occur. Uncommon symptoms include arthritis, coagulation disorders (manifested as bruising and bleeding), intracerebral hemorrhage and acute renal failure, which comprise serious complications. The present study reports the case of 60-year-old patient from Rio de Janeiro state, Brazil, who came into contact with a caterpillar and developed, a few days later, chronic renal disease.Journal of Venomous Animals and Toxins including Tropical Diseases 01/2013; 19(1):14. · 0.43 Impact Factor