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Considerable heterogeneity and ontogenetic changes in venom composition have already been observed in different species of snakes within the Viperidae family. Since the venom of young and adult can cause distinct pathological effects and because the antivenom may be less effective in neutralizing envenoming by young snakes compared to adults, it is of paramount importance to understand the ontogenetic variation of snake venom. Thus, the present study aimed to analyze and compare the venom of Bothrops pauloensis snakes, searching for possible influences of ontogeny and sex in their biochemical and biological aspects. The venom of younger individuals was more complex in relation to high molecular mass proteins, with a greater abundance of metalloproteinases, while adults showed a greater abundance of medium and low molecular mass proteins, such as phospholipases A

Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained fromArtocarpus heterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2/CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3γ N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkin’s lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cells incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell lines sourced from non-Hodgkin’s lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM.

The venom of the Brazilian pit viper

Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from Artocarpusheterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2/CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3γ N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T-cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkin’s lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cell incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell-lines sourced from non-Hodgkin’s lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM.

Scorpionism is a relevant public health problem in several countries in tropical and subtropical regions. In Brazil, Tityus serrulatus sting can induce acute lung injury in part as a consequence of inflammation. Despite the occurrence of other scorpions of Tityus genus in Brazilian scorpiofauna, the knowledge regarding pulmonary alterations is related to T. serrulatus venom (Tsv). Here we studied, comparatively, the pathophysiological changes in the rat airways envenomed by Tsv or T. bahiensis venom (Tbv), since both scorpions are involved in human accidents but with severe envenomations occurring when victims are stung by T. serrulatus. After intravenous injection of the venoms (200 μg/kg), both were able to induce Evans blue extravasation (in 30 min) into airways and increased protein extravasation into lungs at 4 and 24 h, but the magnitude of such events was higher in Tsv group. Hemorrhage (in 60 min) in the lungs was higher in Tbv group, while IL-1β (at 1 h) and IL-6 (at 1 and 4 h) in lung homogenates were detected only in Tsv group. Four and 24 h after envenomation, myeloperoxidase activity in lung was equally augmented in the envenomed groups, as well as an increased in polymorphonuclear cell numbers in bronchoalveolar lavage fluid. At 4 h blood leukogram showed increased leukocyte values with the highest neutrophilia in Tsv group. The numbers of leukocytes and neutrophils remained higher than control at 24 h in Tsv and Tbv groups, and it was accompanied by lympho (envenomed groups) and monocytosis (Tsv group). In conclusion, although Tbv was capable of inducing acute lung injury and blood leukocyte mobilization, most of the evaluated parameters were more affected by the Tsv. These results could help to explain the pathophysiology of the scorpionism and the clinical data arguing toward the greatest severity associated with T. serrulatus stings.

O escorpionismo é importante assunto de saúde pública no Brasil e em vários países, sendo os escorpiões da família Buthidae envolvidos nos acidentes de importância médica. No Brasil, os principais escorpiões dessa família são do gênero Tityus, cujos representantes respondem pela maioria dos acidentes. Os Tityus serrulatus são os principais desencadeadores de acidentes graves no Brasil, quando edema pulmonar pode se instalar e está envolvido com o óbito. Assim, a maioria dos estudos é desenvolvida com sua peçonha, tendo sido demonstrado que desencadeia inflamação sistêmica e pulmonar, com leucocitose, edema e influxo leucocitário para os pulmões. Os escorpiões Rhopalurus rochai também pertencem à escorpiofauna brasileira e à família Buthidae; ocupando regiões de cerrado, pouco habitadas, não existem estudos epidemiológicos ou experimentais acerca da ação da sua peçonha no aparelho respiratório. Investigamos comparativamente a fisiopatologia do escorpionismo experimental em ratos machos, induzido pela administração intravenosa (iv) das peçonhas de T. serrulatus 200 µg/kg (pTs) e R. rochai 200 µg/kg (pRr 200) ou 400µg/kg (pRr 400); animais controles receberam NaCl 0,9% apirogênica iv em mesmo volume que as peçonhas. Foram avaliados parâmetros pulmonares como a permeabilidade vascular por extravasamento de azul de Evans (aE, 30 minutos) e proteínas (por Bradford) no lavado bronco-alveolar (LBA, 4 e 24 horas), hemorragia pela quantificação da cianometahemoglobina (60 minutos), influxo de leucócitos (4 e 24 horas) para os pulmões pela atividade da mieloperoxidase (MPO) e da N-acetil-β-D-glicosaminidase (NAG), e contagem no LBA, e produção de óxido nítrico (NO) nos pulmões pelo método de Griess modificado. Foram avaliadas também a mobilização de leucócitos para o sangue (contagem total e diferencial por microscopia) e produção do NO no coração. As peçonhas induziram aumento da permeabilidade vascular (30 minutos) no aparelho respiratório e acúmulo de proteínas nos pulmões após 24 horas, porém, ambos foram mais afetados pela pTs e só esta promoveu aumento da permeabilidade nos brônquios internos e pulmões, e acúmulo de proteínas em 4 horas. A hemorragia ocorreu nos brônquios internos e pulmão do grupo pTs. A atividade da MPO (4 e 24 horas) e NAG (24 horas), além da concentração de NO nos pulmões (4 e 24 horas), aumentou apenas no grupo pTs. No LBA houve aumento de leucócitos e células mononucleares (4 horas) no grupo pRr 400, enquanto o grupo pTs apresentou aumento de polimorfonucleares da 4ª a 24ª hora quando também ocorreu leucocitose. Alterações no leucograma ocorreram apenas no grupo pTs, com leucocitose, neutrofilia e linfopenia após 4; em 24 horas observou-se adicionalmente linfocitose e monocitose. No coração, apenas a pRr 400 promoveu diminuição de NO abaixo dos controles. Concluímos que a maioria das alterações avaliadas, ocorreram, e foram mais intensas com a pTs; a pRr não pode ser considerada atóxica, mas provavelmente é incapaz de induzir acidentes graves e morte. The scorpionism is a public health issue in Brazil and several other countries and the Buthidae’s family scorpions are involved in accidents medically relevant. In Brazil, the main scorpions of this family belong to Tityus genus, whose representatives account for most of the accidents. Severe envenomation is related mainly to Tityus serrulatus in Brazil, and pulmonary edema is involved in death; thus the majority of studies are developed with its venom. It was demonstrated that the venom from this triggers systemic and pulmonary inflammation, with pulmonary edema, leukocytosis and leukocyte migration to the lungs. The Rhopalurus rochai belong to Brazilian escorpiofauna and to Buthidae family as well; residing in regions of cerrado, poorly inhabited, therefore there are no epidemiological or experimental studies concerning its activity in the respiratory system. The study investigated comparatively the pathophysiology of experimental scorpionism in rats by intravenous (iv) administrations of T. serrulatus venom 200 µg/kg (Tsv) and R. rochai 200 µg/kg (Rrv 200) or 400 µg/kg (Rrv 400). Control group received NaCl 0,9% apyrogenic in the same volume as the venoms. We evaluated pulmonary parameter, such as vascular permeability by Evans blue extravasation (aE, 30 minutes) and proteins (by Bradford method) in bronchoalveolar lavage (BAL, 4 and 24 hours), hemorrhage by cyanomethemoglobin quantification (60 minutes), leukocytes mobilization (4 and 24 hours) to the lungs through the activity of myeloperoxidase (MPO) and N-acetil-β-D-glucosaminidase (NAG), leukocyte counts in BAL, and nitric oxide (NO) production in lung’s parenchyma by modified Griess method. We also evaluated leukocyte mobilization to peripheral blood (total and differential counts through microscopy) and quantified NO in cardiac tissue. Both venoms were able to induce aE extravasation in respiratory tract’s segments and protein accumulation after 24 hours, however both parameters were more affected by Tsv and only this promoted incresead aE in internal bronchi and lungs and protein accumulation in BAL at 4 hours. Hemorrhage occured in lower segments (internal bronchi and lung) only in Tsv group. The activity of MPO (4 and 24 hours), NAG (within 24 hours), and NO content in lungs (4 and 24 hours), were increased only in Tsv group. There was an increase of leukocytes and mononuclear cells in BAL (4 hours) in Rrv 400 group, while Tsv group showed a raise in polymorphonuclear cells, lasting up to the 24th hour (when leukocytosis also occured). Changes in leukogram were found only in Tsv group, with leukocytosis, neutrophilia and lymphopenia after 4 hours; after 24 hours, lymphocytosis and monocytosis also occured. Only Rrv 400 affected the heart, promoting a decrease on NO levels, below those found in NaCl group. We conclude that the majority of the evaluated parameters were more affected by Tsv; and Rrv although not atoxic, probably will not induce severe envenomations nor deaths.