Mast Cells Modulate the Immune Response and Redox Status of the Gastrointestinal Tract in Induced Venom Pathogenesis.

The pathogenesis of Androctonus autralis hector (Aah) scorpion venom involved cellular and molecular mechanisms resulting in multi-organ dysfunction. However, little is reported about the effects of venom on the gastrointestinal axis. Mast cells (MCs) are known to play a crucial role in modulating immune response of the gut. This study aims to investigate the involvement of this cell type in venom-induced gastric and intestinal disorders in a time course (3 and 24h). The obtained results revealed that Aah scorpion venom induced inflammatory cell infiltration as shown by the increase of the myeloperoxidase and eosinophil peroxidase activities. Overexpression of the c-kit receptor (CD117) severely imbalanced the redox status with depletion of antioxidant systemic accompanied by gastrointestinal tissue damage. Moreover, an increased level of lactate dehydrogenase in the serum was correlated with tissue injuries. Pharmacological inhibition of MCs targeting tyrosine kinase (TK) reduces the generation of reactive oxygen species and normalizes catalase, and gluthation S-transferase activities to their physiological levels. In addition, histopathological alterations were restored after pretreatment with c-kit receptor inhibitor associated with a considerable reduction of MC density. Interestingly, obtained results indicate that MCs might be involved in gastric modulation and intestinal inflammation through c-kit signaling following sub-cutaneous Aah venom injection.

Involvement of Toll-like Receptor 4 in Neutrophil-Mediated Inflammation, Oxidative Stress and Tissue Damage Induced by Scorpion Venom.

Systemic inflammatory response and generation of oxidative stress are known to contribute to scorpion venom-induced tissue damage. TLR receptors might represent a link between oxidative stress and inflammation; we therefore investigated whether or not TLR4 is involved in venom-induced immunopathology. The obtained results showed that pharmacological targeting of TLR4 with the selective inhibitor TAK-242 (Resatorvid) prevents the inflammatory response induced by subcutaneous administration of Androctonus australis hector (Aah) venom, as revealed by a significant decrease of neutrophil cell count in peripheral blood associated with significant decline of neutrophil degranulation and sequestration to the lung, liver, and kidney tissues. Moreover, TAK-242 administration inhibited nitrite levels increase in serum, malondialdehyde (MDA), and protein carbonyl tissue contents concomitantly with a significant increase of catalase activity and reduced glutathione (GSH) level in tissue homogenates. Furthermore, venom-induced increases in serum levels of organ dysfunction markers (lactate deshydrogenase, aminotransferase ALT and AST, creatinine and urea) were also significantly suppressed by pre-treatment with TLR4 inhibitor, concordantly with a remarkable improvement in the histological features in lung and liver tissues. The results of the present study indicate the potential role of TLR4 in venom-induced immunopathology and show the in vivo requirement of TLR4 signaling in mediating venom-induced tissue damage.

Serotherapy against Voltage-Gated Sodium Channel-Targeting αToxins from Androctonus Scorpion Venom.

Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. Typically, these venoms contain selective and high affinity ligands for the voltage-gated sodium (Nav) and potassium (Kv) channels that dictate cellular excitability. In the well-studied Androctonusaustralis and Androctonusmauretanicus venoms, almost all the lethality in mammals is due to the so-called α-toxins. These peptides commonly delay the fast inactivation process of Nav channels, which leads to increased sodium entry and a subsequent cell membrane depolarization. Markedly, their neutralization by specific antisera has been shown to completely inhibit the venom's lethal activity, because they are not only the most abundant venom peptide but also the most fatal. However, the structural and antigenic polymorphisms in the α-toxin family pose challenges to the design of efficient serotherapies. In this review, we discuss past and present accomplishments to improve serotherapy against Androctonus scorpion stings.

Differential effect of Androctonus australis hector venom components on macrophage KV channels: electrophysiological characterization.

Neurotoxins of scorpion venoms modulate ion channels. Voltage-gated potassium (KV) channels regulate the membrane potential and are involved in the activation and proliferation of immune cells. Macrophages are key components of the inflammatory response induced by scorpion venom. The present study was undertaken to investigate the effect of Androctonus australis hector (Aah) venom on KV channels in murine resident peritoneal macrophages. The cytotoxicity of the venom was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) -based assay and electrophysiological recordings were performed using the whole-cell patch clamp technique. High doses of Aah venom (50, 125, 250 and 500 µg/ml) significantly decreased cell viability, while concentrations of 0.1-25 µg/ml were not cytotoxic towards peritoneal macrophages. Electrophysiological data revealed a differential block of KV current between resting and LPS-activated macrophages. Aah venom significantly reduced KV current amplitude by 62.5 ± 4.78% (n = 8, p < 0.05), reduced the use-dependent decay of the current, decreased the degree of inactivation and decelerated the inactivation process of KV current in LPS-activated macrophages. Unlike cloned KV1.5 channels, Aah venom exerted a similar blocking effect on KV1.3 compared to KV current in LPS-activated macrophages, along with a hyperpolarizing shift in the voltage dependence of KV1.3 inactivation, indicating a direct mechanism of current inhibition by targeting KV1.3 subunits. The obtained results, demonstrating that Aah venom differentially targets KV channels in macrophages, suggest differential outcomes for their inhibitions, and that further investigations of scorpion venom immunomodulatory potential are required.

Involvement of Alveolar Macrophages and Neutrophils in Acute Lung Injury After Scorpion Envenomation: New Pharmacological Targets.

Androctonus australis hector (Aah) scorpion venom is well known to induce a systemic inflammatory response associated with cell infiltration in lung and edema formation. The present study investigate (i) in vivo the evolution of lung and systemic inflammation triggered by Aah venom and (ii) analyze in vitro the signaling cascade, upstream of inflammatory cytokine expression after Aah venom-stimulated mouse alveolar macrophage (MH-S), the main resident immune cells in the lung. The inflammation induced by Aah venom was assessed in mice through inflammatory cell count, nitric oxide metabolite, and lactate dehydrogenase (LDH) activity in blood, concordantly with neutrophil sequestration in tissue and lung histology. In the in vitro study, MH-S cells are stimulated with Aah venom in the presence of signaling pathway inhibitors, NG25 an inhibitor of transforming growth factor ß-activated kinase (TAK1), PD184352 MAP kinase (MKK)1/2 inhibitor, BI605906 an inhibitor of IKκ-ß (inhibitor of nuclear factor kappa B), and BIRB0796 an inhibitor of p38 MAPK. Obtained results showed that leukocyte transmigration is important in some area of the lung and is closely associated with systemic increase of nitric oxide and LDH. The in vitro study showed that Aah venom induce significantly an increase of the expression of TNF-α, IL-1ß, and MIP-2 in MH-S cells. The pretreatment with inhibitors showed that cytokine increase involves TAK1, IKκ-ß, and ERK1/2 pathways, similarly to Toll-like receptor activation. These findings highlight the contribution of alveolar macrophage and their secretory products to tissue damage and made of TAK1 and ERK1/2, an interesting target in scorpion envenomation.

Switch of Steady-State to an Accelerated Granulopoiesis in Response to Androctonus australis hector Venom.

Although several studies have shown that scorpion venoms cause a systemic inflammatory response syndrome, little is known about the contribution of the hematopoietic organs. The aim of this study was to investigate the effect of Androctonus australis hector venom on the bone marrow and on local inflammatory mediators, in concordance with the systemic inflammatory reaction elicited in mice. The consequences of a direct interaction of venom with murine bone marrow cells were also assessed by in vitro study. Obtained results showed that the early systemic neutrophilia correlated with a rapid granulocyte mobilization. This response was followed by an accelerated granulopoiesis that was supported by TNF-α and IL-6 signals. In vitro data revealed that the venom exerted a proliferative effect on murine hematopoietic cells and stimulated their differentiation towards granulocyte lineage mainly through cytokine secretion. In conclusion, this study indicated that the bone marrow rapidly exerts its activity in response to the experimental envenomation via the granulopoiesis process and inflammatory mediators in concert with the development of a systemic response. The ability of venom to directly switch steady-state granulopoiesis to an accelerated state in vitro could aggravate the disturbance caused by the venom. Better understanding of the mechanisms involved may lead to the emergence of new targets to avoid cell spreading and accumulation by acting on the very early stage of the systemic inflammatory response.

Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line.

BACKGROUND: Several studies have showed that animal venoms are a source of bioactive compounds that may inhibit the growth of cancer cells, which makes them useful agents for therapeutic applications. Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells. METHODS: The cytotoxic and antiproliferative activities were estimated using MTT assay, lactate dehydrogenase release and clonogenic assays. Apoptosis was evaluated by Hoechst 33258 staining, DNA fragmentation assay and caspase-3 activity. Oxidative stress was analyzed by reactive oxygen species, nitric oxide, malondialdehyde and protein carbonyl levels along with assessment of antioxidant status. In addition, alteration of mitochondrial membrane potential was analyzed by JC1 fluorescent dye. RESULTS: The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC50 of 27.05 ± 0.70 µg/mL than venom alone (396.60 ± 1.33 µg/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 µg/mL). Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. Inhibition of NCI-H358 cell proliferation after F3 fraction exposure occurred mainly by apoptosis as evidenced by damaged nuclei, significant DNA fragmentation level and caspase-3 activation in a dose dependent manner. Moreover, F3 fraction enhanced oxidative and nitrosative stress biomarkers and dissipated mitochondrial membrane potential in lung cancer cells along with significant depletion in cellular enzymatic and non-enzymatic antioxidants. Further, the apoptosis induced by F3 fraction was markedly prevented by the antioxidant N-acetylcysteine (NAC) suggesting the potential mechanism of oxidative stress. CONCLUSION: These findings suggest that F3 fraction could induce apoptosis in lung cancer cells through involvement of oxidative stress and mitochondrial dysfunction. Hence, these properties make F3 fraction a promising candidate for development of new anticancer agents.

In vitro studies with renal proximal tubule cells show direct cytotoxicity of Androctonus australis hector scorpion venom triggered by oxidative stress, caspase activation and apoptosis.

Scorpion envenomation injures a number of organs, including the kidney. Mechanisms proposed to explain the renal tubule injury include direct effects of venom on tubule epithelial cells, as well as indirect effects of the autonomic nervous system, and inflammation. Here, we report direct effects of Androctonus australis hector (Aah) scorpion venom on the viability of Renal Proximal Tubule (RPT) cells in vitro, unlike distal tubule and collecting duct cells. Extensive NucGreen nuclear staining was observed in immortalized rabbit RPT cells following treatment with Aah venom, consistent with cytotoxicity. The involvement of oxidative stress is supported by the observations that 1) anti-oxidants mitigated the Aah venom-induced decrease in the number of viable RPT cells, and 2) Aah venom-treated RPT cells were intensively stained with the CellROX(®) Deep Red reagent, an indicator of Reactive Oxygen Species (ROS). Relevance to normal RPT cells is supported by the red fluorescence observed in Aah venom treated primary rabbit RPT cell cultures following their incubation with the Flica reagent (indicative of caspase activation and apoptosis), and the green fluorescence of Sytox Green (indicative of dead cells).

Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line

Several studies have showed that animal venoms are a source of bioactive compounds that may inhibit the growth of cancer cells, which makes them useful agents for therapeutic applications. Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells. Methods: The cytotoxic and antiproliferative activities were estimated using MTT assay, lactate dehydrogenase release and clonogenic assays. Apoptosis was evaluated by Hoechst 33258 staining, DNA fragmentation assay and caspase-3 activity. Oxidative stress was analyzed by reactive oxygen species, nitric oxide, malondialdehyde and protein carbonyl levels along with assessment of antioxidant status. In addition, alteration of mitochondrial membrane potential was analyzed by JC1 fluorescent dye. Results: The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC50 of 27.05 ± 0.70 g/mL than venom alone (396.60 ± 1.33 g/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 g/mL). Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. Inhibition of NCI-H358 cell proliferation after F3 fraction exposure occurred mainly by apoptosis as evidenced by damaged nuclei, significant DNA fragmentation level and caspase-3 activation in a dose dependent manner. Moreover, F3 fraction enhanced oxidative and nitrosative stress biomarkers and dissipated mitochondrial membrane potential in lung cancer cells along with significant depletion in cellular enzymatic and non-enzymatic antioxidants. Further, the apoptosis induced by F3 fraction was markedly prevented by the antioxidant N-acetylcysteine (NAC) suggesting the potential mechanism of oxidative stress. Conclusion: These findings suggest that F3 fraction could induce apoptosis in lung cancer cells through involvement of oxidative stress and mitochondrial dysfunction. Hence, these properties make F3 fraction a promising candidate for development of new anticancer agents.

Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line

Background: Several studies have showed that animal venoms are a source of bioactive compounds that may inhibit the growth of cancer cells, which makes them useful agents for therapeutic applications. Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells. Methods: The cytotoxic and antiproliferative activities were estimated using MTT assay, lactate dehydrogenase release and clonogenic assays. Apoptosis was evaluated by Hoechst 33258 staining, DNA fragmentation assay and caspase-3 activity. Oxidative stress was analyzed by reactive oxygen species, nitric oxide, malondialdehyde and protein carbonyl levels along with assessment of antioxidant status. In addition, alteration of mitochondrial membrane potential was analyzed by JC1 fluorescent dye. Results: The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC50 of 27.05 ± 0.70 μg/mL than venom alone (396.60 ± 1.33 μg/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 μg/mL). Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. Inhibition of NCI-H358 cell proliferation after F3 fraction exposure occurred mainly by apoptosis as evidenced by damaged nuclei, significant DNA fragmentation level and caspase-3 activation in a dose dependent manner. Moreover, F3 fraction enhanced oxidative and nitrosative stress biomarkers and dissipated mitochondrial membrane potential in lung cancer cells along with significant depletion in cellular enzymatic and non-enzymatic antioxidants. Further, the apoptosis induced by F3 fraction was markedly prevented by the antioxidant N-acetylcysteine (NAC) suggesting the potential mechanism of oxidative stress. Conclusion: These findings suggest that F3 fraction could induce apoptosis in lung cancer cells through involvement of oxidative stress and mitochondrial dysfunction. Hence, these properties make F3 fraction a promising candidate for development of new anticancer agents.(AU)

Androctonus australis hector venom contributes to the interaction between neuropeptides and mast cells in pulmonary hyperresponsiveness.

Lung injury and respiratory distress syndrome are frequent symptoms observed in the most severe cases of scorpion envenomation. The uncontrolled transmigration of leukocyte cells into the lung interstitium and alveolar space and pulmonary edema may be the cause of death. Mast cells can release various inflammatory mediators known to be involved in the development of lung edema following scorpion venom injection. The present study was designed to determine the evidence of neurokinin 1 (NK1) receptor and the involvement of mast cell activation to induce pulmonary edema and to increase vascular permeability after Androctonus australis hector (Aah) venom administration. To this end, mast cells were depleted using compound 48/80 (C48/80). Furthermore, the involvement of tachykinin NK1 receptors expressed on mast cell membranes was elucidated by their blocking with an antagonist. On the other hand, the ability of Aah venom to increase vascular permeability and to induce edema was also assessed by measuring the amount of Evans blue dye (EBD) extravasation in bronchoalveolar lavage (BAL) fluid and in the lungs of mice. Pulmonary edema, as assessed by the levels of EBD extravasation, was completely inhibited in compound 48/80-treated animals. Depletion by stimuli non-immunological C48/80 component markedly reduced induced inflammatory response following the venom administration. The mast cells seem to play an important role in the development of lung injury and the increase of vascular permeability in mice following the subcutaneous administration of Aah scorpion venom through the NK1 receptor.

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms.

BACKGROUND: Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). RESULTS: Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury.The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (ß adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. CONCLUSION: These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector(Aah) and Androctonus amoreuxi (Aam). Results Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (β adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming.Conclusion These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Background: Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results: Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (ß adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion: These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.(AU)

Immunomodulation of the inflammatory response induced by Androctonus australis hector neurotoxins: biomarker interactions.

OBJECTIVE: Androctonus australis hector (Aah) is the most dangerous scorpion in the Maghreb countries. Its venom contains three major neurotoxins (Aah I, Aah II and Aah III), which are responsible for almost all the lethal effects caused in mammals. These toxins act on the voltage-gated sodium channels of excitable cells. The targets and the lethal effects of these toxins have been extensively studied. However, their effects on the induced immune response after envenoming have not deeply elicited. We therefore investigated the effects induced by Aah venom and its toxic components, mainly its main toxin Aah II, on the activation of the inflammatory process. METHODS: Wistar rats were injected by intraperitoneal route with a sublethal dose of Aah venom, FTox-G50, the purified Aah II toxin or with 400 µl of sterile physiological saline solution. Immunological biomarkers such as MPO, NO and ICAM-1 were analyzed in serum in lung tissue. Cytokine levels were also determined in serum at 3, 6 and 24 h after envenoming. RESULTS: We report in this study that intraperitoneal injection of the venom or its toxins (the whole toxic fraction or Aah II toxin) caused an inflammatory reaction involving increased neutrophil release into blood and neutrophil accumulation in lung tissue. This cell infiltration was associated with the release of NO, histamine, cytokines (IL-1, IL-6, IL-12, IL-4 and IL-5) and ICAM. CONCLUSION: Aah II binding to its targets, in this case Na⁺ channels, may induce a cascade of events such as inflammatory mediator release and neutrophil migration that could contribute to the exacerbation of the systemic inflammatory response and the development of lung injury following scorpion envenoming.

Lung immunoreactivity and airway inflammation: their assessment after scorpion envenomation.

Release and activation of pro-inflammatory mediators are among the most important induced factors that are involved in the scorpion envenomation pathogenesis. Inflammatory response and lung reactivity were studied in mice following subcutaneous injection with Androctonus australis hector (Aah) venom. Venom immunodetection in lungs and sequestered cell population in the airways were determined. Cytokines, cellular peroxidase activities (eosinophil peroxidase, myeloperoxydase), and IgE antibodies were also assessed. Immunohistochemical study revealed a positive detection of the Aah venom in the alveolar wall, venule lumens, and inside inflammatory cells. Severe lung edema associated with rapid inflammatory response was observed after animal envenomation. Lung neutrophilia and eosinophilia were accompanied with IL-4, IL-5 release, and IgE synthesis. In conclusion, high cytokine levels, recruitment of inflammatory cells (eosinophils and neutrophils), and increased IgE concentration may contribute to the exacerbation and maintenance of the induced inflammatory response in lungs by scorpion venom. These results lead to the better understanding of this induced pathogenesis and could help the physicians to take care of envenomed patients.

Combination of two antibody fragments F(ab')(2)/Fab: an alternative for scorpion envenoming treatment.

Immunotherapy is the only effective treatment for scorpion stings. However the efficiency of this treatment varies depending on the forms of the antibodies and route of administration used. The antibodies are mostly injected as F(ab )(2) fragments. In this study, we investigated damage to the heart and lung tissue and the inflammatory response caused by Androctonus australis hector venom, its toxic fraction after molecular filtration or the isolated main alpha toxin (Aah II) in the presence or absence of different antibody molecules. A mixture of antibody fragments, F(ab )(2) and Fab, significantly reduced local leukocytosis, hemorrhage and inflammatory oedema induced by the A. australis hector venom and its toxins.

Pathophysiological effects of Androctonus australis hector scorpion venom: tissue damages and inflammatory response.

In this study, the effects of sublethal dose of Androctonus australis hector (Aah) venom on the enzymatic activities (creatine phospho-kinase and lactate dehydrogenase) and histopathological changes of heart and lungs' organs were determined 24h following envenoming NMRI mice. The effects of Aah venom on the lytic activity of the complement system, plasma cytokine rates (IL1-beta, IL-6, TNF-alpha, IL-4 and IL-10) and the peripheral blood cell infiltration were also studied. Microscopically, treated animals showed severe myocardial edema, hemorrhages and necroses and severe acute bronchopneumonia with alveolar edema and hemorrhages. High serum levels of lactate dehydrogenase and creatine kinase correlate to the tissue lesions. The results showed fast kinetics of production of pro-inflammatory (IL1-beta, IL-6, TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokines at 30min in blood sera. An increase in serum lytic activity of envenomed animals and leucocytosis in peripheral blood with predominance of mononuclear and neutrophil cells were also observed. In conclusion, the results reported in the present study suggest that pathophysiological manifestations of Aah envenomation may be mediated sequentially or simultaneously by cytokines and the complement system, which in turn activate leukocyte to produce tissue damage.

Epidemiological data, clinical admission gradation and biological quantification by ELISA of scorpion envenomations in Algeria: effect of immunotherapy.

An epidemiological and biological survey of scorpion envenomation was conducted in Algeria. Analysis of 182 medical files showed that 70% of the patients were stung by Androctonus australis. Most accidents occurred during the morning (40%) or the evening (30%). Two-thirds of the patients reached a hospital 1 hour after being stung. Their clinical symptoms classified 78% of them as Grade I (mild envenomation) and 17% of them as Grade II (moderate envenomation) on admission to hospital. No severe envenomation (Grade III) was reported. Most patients were treated with antivenom by the intramuscular route. Blood samples were collected before and after antivenom immunotherapy. A good correlation was observed between the grade of envenomation on admission and the blood venom concentrations measured by ELISA. The venom concentration decreased as function of the interval between the sting and blood collection (t1/2 = 2 h). Intramuscular injection of 10 ml of antivenom did not efficiently neutralize scorpion venom. Inflammation was followed by measuring IL6 concentration. IL6 peaked 1 h after scorpion envenomation. This study shows that optimization of the administration of antivenom is required to achieve clinical efficiency. In particular, intravenous injection of a larger dose of a more potent antivenom should be considered.