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.

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.

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

Because of their venom lethality towards mammals scorpions of the 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 (Na) and potassium (K) channels that dictate cellular excitability.

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

Neurotoxins of scorpion venoms modulate ion channels. Voltage-gated potassium (K) 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.

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.

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.

Cytotoxic activity of 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 (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells.

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.

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.

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.

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.

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.

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.

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.

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%).