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With its enormous geographical extent and various ecosystems, Algeria has more than 54 species of scorpions. Among these species, Androctonus australis (Linnaeus, 1758) is the species with the highest medical importance. This study particularly concerned this species' seasonal variation and developmental stages, which were collected from various environments in the Sahara Desert of Algeria. The present study focuses on the annual activity of scorpions (phenology) of A. australis in the region of Ghardaïa. Twelve nocturnal outings at mid-month during 2022 made it possible to collect 208 scorpions. Results allowed us to define the favorable mating season of A. australis that occurs during the autumn period (15th November to 10th August) when climatic conditions are favorable for courtship, which means temperatures relatively low (around 18°C) and winds blowing at a regular speed and constant direction. We also noted that the species develops a winter diapause lasting from 5 to 6 months, covering the whole winter season and a few weeks of spring. During spring and summer, as a result of parturition, a huge number of juveniles are observed. [ABSTRACT FROM AUTHOR]

This work consists to evaluate in vitro the activity of scorpion venom Androctonus australis (Linnaeus, 1758) which is the most abundant and most dangerous species in Algeria, against five bacterial strains: Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus aureus MRSA and Micrococcus luteus. Biological tests by the use of different concentrations of venom aims to investigate the minimum inhibitory concentration is measured by optical density by the method of diffusion in a liquid medium. Whose, the bacterial inoculum using a UV-Visible spectrophotometer at a wavelength of 600 nm. While statistical analyses are applied to the observed results to conclude the antibacterial effect of scorpion venom. The results showed that no antibacterial activity of the A. australis venom against all bacterial strains tested. Nevertheless, the S. aureus MRSA strain exhibited greater resistance than other bacterial strains. [ABSTRACT FROM AUTHOR]

In terrestrial legged locomotion, the distribution of mass can influence the gait characteristics. This can be due to a change in the magnitude or distribution of the load. The latter occurs in scorpions when they lift their large metasoma from a trailing position in ambulatory posture to the well-known arched forward position in the defensive posture. We measured how locomotion changes between these two postures by recording scorpions walking using high-speed video. We found that the metasoma in the fat-tailed scorpion (Androctonus australis) represents about a quarter of the total mass. Moving this mass anteriorly over the body changes the position of the center of mass forward 8.15 ± 1.86 mm. We found this increases the overall duty factor, and particularly that of the second leg pair, even when taking the reduced speed in defensive posture into account. In the five scorpions we recorded, also the ipsilateral phase of leg pairs 3 and 4 differed in defensive posture. We found that the trajectory the 4th foot describes during a single stride also differed significantly between postures, showing this to be a sensitive measure of changes in gait. The change from an ambulatory to a defensive posture places different demands on the gait of scorpions, possibly largely due to the forward displacement of the center of mass. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present work is a study of composition and structure of scorpion fauna in the region of Ouargla (Eastern Algerian Sahara), during a period of fourteen years from 2005 to 2018, we sampled from different biotopes more than 1550 adult specimens, divided into nine 9 species of scorpions: Androctonus amoreuxi, Androctonus australis, Buthacus arenicola, Buthacus samiae, Buthiscus bicalcaratus, Buthus saharicus, Buthus tunetanus, Orthochirus innesi, and Scorpio punicus. A. australis was the most abundant species with 47.36% of the total individuals captured. Other species such as S. punicus, B. arenicola and A. amoreuxi are ranked as accidental with rates less than 20%. Among the important results in this work is reporting for the first time the presence of B. bicalcaratus in Ouargla and the new records of B. samiae and B. saharicus in this area. The Shannon's index was H' = 2.05 and the evenness index was 0.65, showing a very important diversity of scorpions with more than 23.5% of scorpion species reported in Algeria; however, a poor balance between the number of sampled species with dominance of the thermophilic species that are the most adapted scorpions in this arid climate. [ABSTRACT FROM AUTHOR]

Objective: Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. It is purified from Androctonus australis scorpion venom. The binding of KTX2 to its targets is able to alter the neuronal excitability leading to neurological disorders, accompanied by an inflammatory response. In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. The aim of this study is to evaluate the effect of insulin injected by i.c.v. route on the neuro-pathophysiological and systemic disorders induced by KTX2.Materials and methods: Tissue damage, inflammatory response and oxidative stress biomarkers were assessed in NMRI mice at 24 h after co-injection of KTX2 and insulin by intracerebroventricular route.Results: Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema and blood-brain barrier alteration induced by KTX2, these are accompanied by significant decrease of systemic disorders including serum cytokines, inflammatory and oxidative stress markers and tissue damage.Conclusion: These results indicate that insulin is able to reduce neuro-immunological effects and systemic disorders induced by KTX2. The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain. [ABSTRACT FROM AUTHOR]

Androctonus australis is one of the most ubiquitous and common scorpion species in desert and arid lands from North Africa to India and it has an important ecological role and social impact. The bacterial community associated to this arachnid is unknown and we aimed to dissect its species composition in the gut, gonads, and venom gland. A 16S rRNA gene culture‐independent diversity analysis revealed, among six other taxonomic groups (Firmicutes, Betaproteobacteria, Gammaproteobacteria, Flavobacteria, Actinobacteria, and Cyanobacteria), a dominance of Mollicutes phylotypes recorded both in the digestive tract and the gonads. These related Mollicutes include two Spiroplasma phylotypes (12.5% of DGGE bands and 15% of clones), and a new Mycoplasma cluster (80% of clones) showing 16S rRNA sequence identities of 95 and 93% with Mollicutes detected in the Mexican scorpions Centruroides limpidus and Vaejovis smithi, respectively. Such scorpion‐associated Mollicutes form a new lineage that share a distant ancestor with Mycoplasma hominis. The observed host specificity with the apparent phylogenetic divergence suggests a relatively long co‐evolution of these symbionts with the scorpion hosts. From the ecological point of view, such association may play a beneficial role for the host fitness, especially during dormancy or molt periods. [ABSTRACT FROM AUTHOR]

Scorpions in the Khenchela region (northeast of Algeria) are almost neglected. That is why this study concerns the census of the scorpion fauna in this region. A monthly collecting of scorpions during the period from March 2015 to February 2016 in three biotopes (edge of a dam, palm grove, and pine forest) of 3 districts (Babar, Chechar, and El-Hamma), resulted in the capture of 76 adults. Four species of scorpions were identified: Androctonus australis, Buthus aures, B. tunetanus (Family Buthidae), and Scorpio maurus (Family Scorpionidae). [ABSTRACT FROM AUTHOR]

An attenuated nanovaccine (Nps – V ∗ ) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps – V ∗ nanovaccine developed against Androctonus australis hector ( Aah ) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100 μg of irradiated Aah venom (V ∗ ) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500 μg of V ∗ -loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps – V ∗ did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps – V ∗ and supported its use in superior animal tests, then in a Phase 1 clinical trial. [ABSTRACT FROM AUTHOR]

In regions at risk of scorpion envenomation, children remain the principal victims; they exhibit severe symptoms and represent a higher mortality rate compared to adults. The pathophysiology of envenomation is related to an excessive inflammatory response; however, no studies have identified the differences in immune responses to scorpion stings and mainly the mechanisms of inflammation between children and adults, which may be a determinant key of the susceptibility of children to scorpion envenomation. In this study, we compared the systemic (blood and lung) and the central (brain) inflammatory responses after injection of Androctonus australis hector ( Aah) venom to 7 and 21 postnatal days (pnds) and adult mice by subcutaneous route. Results revealed that 7 and 21 pnd mice were more sensitive to Aah venom than adults and presented also severe systemic and central inflammatory responses characterized by a high activation of immune cells, NO liberation, and lipid peroxidation. Lymphocyte levels were much lower in young animals than in adults; however, neutrophil levels seemed to be higher in immature mice. The antioxidant GSH and catalase levels were more reduced in 7 and 21 pnd mice compared to adults leading to more pronounced tissular alterations and edema formation in lung and brain. These findings show a relationship between the severity of the pathophysiological effects of Aah venom and the age. The vulnerability of immature animals to Aah venom might result from uncontrolled inflammatory response and central nervous system alterations. Data from the present study emphasize the need for the development of age-specific therapeutic modalities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

New bionic function surface inspired from desert scorpion was developed for erosion resistance application in this research. Three elements, bump, groove-shape and curvature, were applied on the surface. Using of Stereo Microscope, the micro-structures of the scorpion ( Androctonus australis ) were analyzed. According to information, bionic samples were manufactured. Solid particle erosion behavior is investigated using a blasting jet machine at particle impact angle (30°) and stress of air compressor is 0.5 MPa. The experimental results of bionic samples were compared with traditional smooth sample and each other, respectively. Results of erosion test and Scanning Electron Microscope (SEM) were selected as evaluation standard and explored anti-erosion mechanisms of these micro-structures which were on the bionic surface. The experimental results show that bionic samples have superior solid particle erosion resistance than traditional smooth sample, owing to the micro-structures on the surface. Referring to the analysis, both the bump and curvature can improve the anti-erosion performance by changing the relative impact angle which is compared to the surface of sample. [ABSTRACT FROM AUTHOR]

Background: Within the scorpion family Buthidae, some of the most dangerous venomous genera are Androctonus ( A ), Buthus ( B ), and Leiurus ( L ). This venom is valuable raw material for numerous therapeutic formulations because of its pharmacological potential; however, because of its high prices in the global market, fake "venom mixes" are being made to market illegally, and it is important that these unknown mixes be evaluated. A fast and accurate response to the request for this identification is necessary., Method: This study was conducted in Turkey in 2022. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) is a linear positive-ionization mode was used for identification of scorpion species. The mass spectra of the three scorpion venoms were examined in detail. The peptide and protein profiles in the venoms of congenerous three scorpion venoms and the proportional differences in these venoms were investigated. For interspecific variation, a principal component analysis of all venoms was conducted, and variance values and distance-proximity indices were determined., Results: The top three peptide masses in the highest relative abundance for A. australis , B. mardochei , and L. quinquestriatus quinquestriatus , respectively, were 6901, 7431, and 7447; 4238, 5283, and 4055; and 3828, 7868, and 6799 Da. While the variance rate between A. australis and the other two venoms was 40%, this rate was 38% between B. mordochei and L. quinquestriatus quinquestriatus venoms., Conclusion: A very simple protocol of species identification using scorpion venom samples was created using recent advances in MALDI-TOF MS., (Copyright © 2023 Numanoğlu Çevik. Published by Tehran University of Medical Sciences.)

We report the detailed chemical, immunological and pharmacological characterization of the α-toxin Bot IX from the Moroccan scorpion Buthus occitanus tunetanus venom. Bot IX, which consists of 70 amino acids, is a highly atypical toxin. It carries a unique N-terminal sequence extension and is highly lethal in mice. Voltage clamp recordings on oocytes expressing rat Nav1.2 or insect BgNav1 reveal that, similar to other α-like toxins, Bot IX inhibits fast inactivation of both variants. Moreover, Bot IX belongs to the same structural/immunological group as the α-like toxin Bot I. Remarkably, radioiodinated Bot IX competes efficiently with the classical α-toxin AaH II from Androctonus australis, and displays one of the highest affinities for Nav channels. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

To enhance humoral defense against diseases, vaccine formulation is routinely prepared to improve immune response. Studies in nanomaterials as a carrier of vaccine delivery are promising and interesting. In this study, attenuated Androctonus australis hector ( Aah ) venom and its toxic fraction were encapsulated into different formulations inside calcium–alginate nanoparticles (Ca–Alg Nps), and used as a vaccine delivery system against scorpion envenomation. Ca–Alg Nps were prepared by ionic gelation and characterized. An immunization schedule was undertaken in rabbits in order to study how Aah venom entrapped in Ca–Alg Nps might induce protective immunity. Results showed the influence of different parameters on the suitable nanoparticle formation. They also showed no toxicity of free Ca–Alg Nps and a different inflammatory profile depending on the nanovaccine formulations. More interestingly, evaluation of specific IgG titer and IgG1/IgG2a isotype balance revealed a protective effect with the nanoparticles encapsulating the attenuated antigens. Challenge up to 6 LD 50 of native venom, allowed to an important immunoprotection of all immunized rabbits, with no recorded death. Taken together and with respect to the properties of nanoparticles and high immunogenicity, calcium–alginate nanoparticles could be considered as a new promising adjuvant system and a vaccine delivery against scorpion envenomation. [ABSTRACT FROM AUTHOR]

The adoption of pest-resistant transgenic plants to reduce yield losses and decrease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AaIT/GNA, in which an insecticidal scorpion venom neurotoxin ( Androctonus australis toxin, AaIT) is fused to snowdrop lectin ( Galanthus nivalis agglutinin, GNA). Compared with transgenic tobacco and Arabidopsis plants expressing AaIT or GNA, transgenic plants expressing AaIT/GNA exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AaIT/GNA showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AaIT/GNA exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AaIT/GNA fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops. [ABSTRACT FROM AUTHOR]

Context: The nature of scorpion-related cardiomyopathy is still a matter of debate where specific toxin-induced cardiomyopathy, ischemic, or catecholaminergic cardiomyopathy is advocated as well. We report two cases of Takotsubo syndrome following envenomation by Androctonus australis, bringing new evidence for the fundamental role of catecholamines in the pathogenesis of this cardiomyopathy. Case 1: A woman aged 36 presented with pulmonary edema and shock following scorpion envenomation. Echocardiography-Doppler showed a LVEF at 30%. Cardiac magnetic resonance (CMR) imaging showed a basal ballooning of the left and right ventricles suggestive of an inverted biventricular Takotsubo syndrome. A second CMR performed after recovery was normal. Case 2: A woman aged 45 was admitted for pulmonary edema and shock consecutive to scorpion envenomation. Echocardiography showed a LVEF at 35%. CMR showed a basal ballooning. The patient was discharged four days following admission with a normal LV function on repeat echocardiography examination. Conclusions: Cardiomyopathy in these cases, following scorpion envenomation by Androctonus australis, fulfills the criteria of Takotsubo syndrome. These observations contribute to our understanding of the mechanism, prognosis, and treatment of scorpion-related cardiomyopathy. [ABSTRACT FROM AUTHOR]

Envenomation is a public health problem in many regions of the world. The only available treatment is the serotherapy that has limited efficiency due to the delay of its administration. The goal of this study is to provide a new and more efficient alternative to this treatment. A comparative study of the effects of two adjuvants in their ability to enhance the efficiency of the detoxified and safe antigens to produce a long lasting immunoprotection is undertaken using Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with Androctonus australis hector ( Aah ) detoxified venom, and compare their effects on the immune system. Immunization schedule was performed with two groups of rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant preparations, once a month during three months. Blood samples were collected each week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase (EPO) activities and antibody titer. After four months from the last immunization, rabbits were challenged with increased doses of native Aah venom. Results showed that MF59 effect was immediate in the first 24 h post-immunization by activating the recruitment of lymphocytes, monocytes and neutrophils, while Alum adjuvant effect seems to be delayed, and appeared in the second week after immunization. An important cell infiltration was observed with Alum preparation, due to its specific local depot effect. However, immunized animals with MF59 preparation challenged with the native venom showed a protective effect against its toxicity until 6 LD50 compared to those immunized with Alum preparation which are only protected at 4 LD50. One week after challenge, only immunized animals with Alum preparation present an increase in cell infiltration, MPO and EPO activities. These results are correlated with the ability of MF59 adjuvant to induce a potent immunoprotective effect against Aah venom compared to Alum adjuvant. [ABSTRACT FROM AUTHOR]

Some venom components are known to present potential biological activities that are useful as tools in therapeutics. In this study anti-tumoral activity of Androctonus australis hector ( Aah ) venom and its purified fraction on early step of hepato-carcinogenesis initiated by Fumonisin (FB1), was tested. Initiated hepatic tumor was assessed in mice by decreased doses of Fumonisin B1 associated to phenobarbital. Scorpion venom was used to investigate its activity on initiated tumor by FB1. Evaluation of oxidative unbalance, enzymatic activities and DNA quantification in the liver were correlated with tissue analysis. Obtained results showed that the initiated pathogenesis by FB1 at seven months was characterized by tissue alterations and biomarker variations. These alterations were characterized by atypical lesions such as muffled nucleus, karyo- and cyto-megaly; up normal and large number of nuclei into hepatocytes. These alterations were confirmed by DNA alteration. An unbalance of oxidative status was also observed, characterized by an increased levels of respectively oxidant (NO and MDA) and antioxidant (GSH and catalase activity) mediators. Aah venom and its non-toxic fraction used at low doses seemed to be able to restore partially the hepatic altered tissue induced by FB1. Decreased levels of oxidative and anti-oxidative mediators were also observed. DNA in hepatocytes returned also to the physiological values. Structure of hepatic tissue showed restoration of some alterations such as karyo- and cyto-megaly; decrease of polyploidy hepatocytes induced by FB1. Aah venom and its non-toxic fraction seem to contain some bioactive components with anti-tumoral activity. Purification of this activity from non-toxic fraction F1 could be of interest to identify the components with anti-tumoral activities. [ABSTRACT FROM AUTHOR]

To evaluate the dose-effects of Androctonus australis hector (Aah) venom injected subcutaneously on hemodynamics and neurohormonal secretions, 10 anesthetized and ventilated mongrel dogs, were split in two groups (n = 5/group). Subcutaneous injection was done with either 0.2 mg/kg or 0.125 mg/kg of the purified G50 scorpion toxic fraction. Hemodynamic parameters using right heart catheter were recorded and plasma concentrations of catecholamine, troponin, and serum toxic fraction were measured sequentially from baseline to 120 min. We identified the dose of toxic fraction evoking characteristic hemodynamic perturbation of severe envenomation, the time-lapse to envenomation, and the associated plasma level. The injection of 0.125 mg/kg toxic fraction was not associated with significant variations in hemodynamic parameters, whereas the 0.2 mg/kg dose caused envenomation characterized by significant increase in plasma catecholamines, increased pulmonary artery occluded pressure, mean arterial pressure, and systemic vascular resistance (p < 0.05), in association with sustained decline in cardiac output (p < 0.001). Envenomation occurred by the 30th minute, and the corresponding concentration of toxic fraction was 1.14 ng/ml. The current experiment allowed the identification of the sub-lethal dose (0.2 mg/kg) of the toxic fraction of Aah administered by the subcutaneous route. Two parameters with potential clinical relevance were also uncovered: the time-lapse to envenomation and the corresponding concentration of toxic fraction. [ABSTRACT FROM AUTHOR]

Androctonus australis hector scorpion venom is well known by its high toxicity, it induces massive release of neurotransmitters that lead to pathophysiological disorders in cardiovascular, neuro-hormonal and immune systems. Previous studies have shown the relationship between the severity of scorpion envenoming and immune system activation. This study was assessed to investigate the involvement of complement system and inflammatory mediators after sublethal injection of Aah venom, its toxic fraction (FtoxG50) and its main toxins (AahI and AahII) into NMRI mice. The Activation complement system by the venom is also compared to that induced of lipoplysaccharides (LPS). Obtained results showed that seric complement system (CS) is activated by the venom and by its toxic components; this activation is more pronounced into liver tissue when toxic components (FtoxG50, AahI or AahII) are used. Increase of cytokine levels (IL1β, TNFα and ICAM) into hepatic tissue induced by AahI or AahII neurotoxins is correlated with tissue alterations. Aprotinin, a non specific inhibitor of complement system seems to be able to reduce CS consumption and to restore partially the induced tissue damage by venom. The mechanisms by which toxic fraction or LPS induced the activation of complement system seem to be different. Sensitivity of hepatic tissue is more pronounced after FtoxG50 injection; however lung tissue is more sensible to LPS than FoxG50. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We have purified the AaTX1 peptide from the Androctonus australis (Aa) scorpion venom, previously cloned and sequenced by Legros and collaborators in a venom gland cDNA library from Aa scorpion. AaTX1 belongs to the α-Ktx15 scorpion toxins family (αKTx15-4). Characterized members of this family share high sequence similarity and were found to block preferentially I A- type voltage-dependent K + currents in rat cerebellum granular cells in an irreversible way. In the current work, we studied the effects of native AaTX1 (nAaTX1) using whole-cell patch-clamp recordings of I A current in substantia nigra pars compacta dopaminergic neurons. At 250 nM, AaTX1 induces 90% decrease in I A current amplitude. Its activity was found to be comparable to that of rAmmTX3 (αKTx15-3), which differs by only one conserved (R/K) amino acid in the 19th position suggesting that the difference between R19 and K19 in AaTX1 and AmmTX3, respectively, may not be critical for the toxins' effects. Molecular docking of both toxins with Kv4.3 channel is in agreement with experimental data and suggests the implication of the functional dyade K27-Y36 in toxin-channel interactions. Since AaTX1 is not highly abundant in Aa venom, it was synthesized as well as AmmTX3. Synthetic peptides, native AaTX1 and rAmmTX3 peptides showed qualitatively the same pharmacological activity. Overall, these data identify a new biologically active toxin that belongs to a family of peptides active on Kv4.3 channel. [ABSTRACT FROM AUTHOR]

Several diagrams related to toxins including Trittame loki's toxins, androctonus australis and tityus serrulatus, are presented.

Abstract: Voltage-gated Na+ channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins’ effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5nM and 1μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8nM and 1.76μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na+ channels in nociceptors. [Copyright &y& Elsevier]

Background: Scorpion venom induces systemic inflammation characterized by an increase in cytokine release and chemokine production. There have been few experimental studies assessing the effects of scorpion venom on adipose tissue function in vivo. Methodology/Principal Findings: To study the adipose tissue inflammation (ATI) induced by Androctonus australis hector (Aah) venom and to assess possible mechanisms of ATI, mice (n = 6, aged 1 month) were injected with Aah (0.45 mg/kg), toxic fraction of Aah (FTox-G50; 0.2 mg/kg) or saline solution (control). Inflammatory responses were evaluated by ELISA and cell sorting analyses in adipose tissue 45 minutes and 24 hours after injection. Quantitative real-time PCR was used to assess the regulation of genes implicated in glucose uptake. The titers of selected inflammatory cytokines (IL-1β, IL-6 and TNF-α) were also determined in sera and in insulin target tissues. The serum concentration of IL-1β rose 45 minutes after envenomation and returned to basal level after 24 hours. The pathophysiological effects of the venom after 24 hours mainly involved M1-proinflammatory macrophage infiltration in adipose tissue combined with high titers of IL-1β, IL-6 and TNF-α. Indeed, TNF-α was strongly induced in both adipose tissue and skeletal muscle. We studied the effects of Aah venom on genes implicated in insulin-stimulated glucose uptake. Insulin induced a significant increase in the expression of the mRNAs for hexokinase 2 and phosphatidylinositol 3-kinase in both skeletal muscle and adipose tissue in control mice; this upregulation was completely abolished after 24 hours in mice envenomed with Aah or FTox-G50. Conclusions/Significance: Our findings suggest that Aah venom induces insulin resistance by mechanisms involving TNF-αdependent Map4k4 kinase activation in the adipose tissue. [ABSTRACT FROM AUTHOR]

The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic α-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage activated Na+ channels. However, the high antigenic polymorphism of α-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 Å-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 Å-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah α-toxins and suitable for immunotherapy. [ABSTRACT FROM AUTHOR]

Androctonus australis is primarily involved in envenomations in North Africa, notably in Tunisia and Algeria, and constitutes a significant public health problem in this region. The toxicity of the venom is mainly due to various neurotoxins that belong to two distinct structural and immunological groups, group I (the AahI and AahIII toxins) and group II (AahII). Here, we report the use of a diabody mixture in which the molar ratio matches the characteristics of toxins and polymorphism of the venom. The mixture consists of the Db9C2 diabody (anti-group I) and the Db4C1op diabody (anti-AahII), the latter being modified to facilitate in vitro production and purification. The effectiveness of the antivenom was tested in vivo under conditions simulating scorpion envenomation. The intraperitoneal injection of 30 μg of the diabody mixture protected almost all the mice exposed to 3 LD50 s.c. of venom. We also show that the presence of both diabodies is necessary for the animals to survive. Our results are the first demonstration of the strong protective power of small quantities of antivenom used in the context of severe envenomation with crude venom. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: AaCtx is the first chlorotoxin-like peptide isolated from Androctonus australis scorpion venom. Its amino acid sequence shares 70% similarity with chlorotoxin from Leiurus quinquestriatus scorpion venom, from which it differs by twelve amino acids. Due to its very low concentration in venom (0.05%), AaCtx was chemically synthesized. Both native and synthetic AaCtx were active on invasion and migration of human glioma cells. However, their activity was found to be lower than that of chlorotoxin. The molecular model of AaCtx shows that most of amino acids differing between AaCtx and chlorotoxin are localized on the N-terminal loop and the α-helix. Based on known compounds that block chloride channels, we suggest that the absence of negative charged amino acids on AaCtx structure may be responsible for its weak activity on glioma cells migration and invasion. This finding serves as a starting point for structure–function relationship studies leading to design high specific anti-glioma drugs. [Copyright &y& Elsevier]

A synthetic scorpion Hector Insect Toxin ( AaHIT) gene, under the control of a CaMV35S promoter, was cloned into cotton via Agrobacterium tumefaciens-mediated transformation. Southern blot analyses indicated that integration of the transgene varied from one to more than three estimated copies per genome; seven homozygous transgenic lines with one copy of the T-DNA insert were then selected by PCR and Southern blot analysis. AaHIT expression was from 0.02 to 0.43% of total soluble protein determined by western blot. These homozygous transgenic lines killed larvae of cotton bollworm ( Heliothis armigera) by 44–98%. The AaHIT gene could used therefore an alternative to Bt toxin and proteinase inhibitor genes for producing transgenic cotton crops with effective control of bollworm. [ABSTRACT FROM AUTHOR]

Abstract: The improvement of the immunotherapeutic treatment of envenomations requires a better knowledge of the pharmacological actions of the scorpion venom and of the mechanism of its in vivo neutralization by antivenom. In the present work, we determined the toxicokinetic parameters of the toxic fraction of Androctonus australis garzonii venom in the absence and after antivenom immunotherapy, in experimentally envenomed rabbits. After subcutaneous injection of the scorpion venom, toxins showed a fast and complete resorption from the site of injection associated with a simultaneous distribution in a large extracellular compartment and with an important body clearance. The precocious intravenous injection of an appropriate antivenom dose was shown to induce an immediate, complete and durable neutralization of toxins, as well as their rapid redistribution from the peripheric compartment to the vascular one. On the contrary, the intramuscular injection of the same antivenom dose produced a slower and partial redistribution of toxins, leading to a delayed neutralization of the venom. The intravenous injection of smaller antivenom doses induced transient decreases of circulating toxins, indicating that a minimal antivenom dose has to be administered to allow an efficient and durable neutralization of the venom. We concluded also that this minimal effective dose of antivenom has to be injected precociously, by intravenous route, to achieve an efficient immunotherapy. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Antibody-based therapy is the only specific treatment for scorpion envenomation. However, there are still major drawbacks associated with its use; mainly because antivenoms are still prepared from immune equine serum raised against crude venoms, whereas only a limited number of neurotoxins are responsible for the lethality of the venom. Using a murine hybridoma that secretes a well-characterized neutralizing IgG directed to neurotoxins AahI and AahIII from the venom of the scorpion Androctonus australis, we constructed a recombinant Fab (rFab) fragment, which was produced and purified from transformed bacteria. It recognized toxin AahI with a high affinity (KD=8.2×10−11 M) equivalent to the homologous pFab prepared by papain digestion of whole IgG. Although the AahI-neutralizing capacity of protein L-purified rFab was low compared to other recombinant antibody formats (scFv and diabody) investigated in parallel, the antibody engineering approach presented here provides an innovative way to synthesize novel toxin-neutralizing molecules. It may serve as a strategy for designing a new generation of antivenoms. [Copyright &y& Elsevier]