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ABSTRACT
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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.... more
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.
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Research Interests: Immunology, Immune response, Biology, Atherosclerosis, Cytokines, and 15 moreInflammation, Medicine, Humans, Animals, Male, Clinical Sciences, Chemokine, Immune system, Biological markers, Lung Injury, Inflammatory response, Medical and Health Sciences, Cardiovascular medicine and haematology, Medical biochemistry and metabolomics, and Inflammation Mediators
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)... more
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.
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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.... more
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.
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Research Interests: Pharmacology, Chemistry, Immunology, Inflammation, Oxidative Stress, and 4 moreMedicine, Venom, Scorpion, and TLR
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Research Interests: Microbiology, Biology, Antimicrobial Peptides, Bacteria, Venom, and 4 moreDefensin, Peptide, Antimicrobial, and Scorpion
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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... more
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 Androctonus australis and Androctonus mauretanicus 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 str...
Research Interests: Pharmacology, Chemistry, Medicine, Venom, Toxins, and 6 moreAntivenom, Sodium channel, Toxin, Scorpion, Depolarization, and Serotherapy
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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... more
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...
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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... more
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 ass...
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Scorpion envenomation remains an important health problem in many countries in the world, especially in North Africa, Asia and America. In Algeria, the most dangerous species for humans are Androctonus australis hector (Aah) and Buthus... more
Scorpion envenomation remains an important health problem in many countries in the world, especially in North Africa, Asia and America. In Algeria, the most dangerous species for humans are Androctonus australis hector (Aah) and Buthus occitanus tunetanus (Bot). These scorpions are responsible for the apparition of various symptoms in envenomed patients such as: pain, hypertention, hypotension, sudation and fever. An aggravation of clinical conditions of envenomed patients is characterized by a pulmonary cedema and myocardial damage. The evaluation of the severity of scorpion envenoming by immuno-enzymatic assay requires firstly, the preparation of a specific anti-horse F(ab')2 peroxydase conjugate not yet commercialized. The restatement of conditions of ELISA sandwich test allowed its utilization in determination of the venom concentration in envenomed patients and rats sera after envenoming by scorpion venom. Standardization of this test, its reproductibility, linearity and it...
Research Interests: Biology, Adolescent, Medicine, Mali, Humans, and 15 moreChild, Female, Pubmed, Animals, Male, Infant, Antivenom, Middle Aged, Rats, Adult, Envenomation, Scorpion, Enzyme Linked Immunosorbent Assay, Child preschool, and Antivenins
Scorpion envenoming is a serious public health problem in many areas in the world. The most dangerous scorpion species in Algeria are Androctonus australis hector (Aah). Little is known about biochemical and histopathological effects of... more
Scorpion envenoming is a serious public health problem in many areas in the world. The most dangerous scorpion species in Algeria are Androctonus australis hector (Aah). Little is known about biochemical and histopathological effects of Androctonus australis hector venom after experimental envenomation. In this study, the effects of sublethal dose and lethal dose 50 (LD50) of Aah venom on the enzymatic activities (transaminases, alkaline phosphatase, creatine kinase and lactate dehydrogenase) and histopathological changes from organs (liver, heart, kidneys and lungs) were determined 24 hr following envenoming (s.c) of the mice. The effect of F(ab')2 fragments anti-FToxG-50-Aah was also tested on the same organs. The histopathological studies following Aah envenoming showed degenerative changes in the liver where most hepatocytes were enlarged and necrotic. Nuclei were irregular in size. After envenoming with Aah venom the myocardium showed myocytolysis with interstitial edema an...
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This paper reports the simultaneous determination of toxicokinetic and toxicodynamic properties of Androctonus australis hector venom, in the absence and presence of antivenom (F(ab')(2) and Fab), in envenomed rats. After... more
This paper reports the simultaneous determination of toxicokinetic and toxicodynamic properties of Androctonus australis hector venom, in the absence and presence of antivenom (F(ab')(2) and Fab), in envenomed rats. After subcutaneous injection of the venom, toxins showed a complete absorption phase from the site of injection associated with a distribution into a large extravascular compartment. The injection of Fab and F(ab')(2) induced the neutralization of venom antigens in the blood compartment, as well as the redistribution of venom components from the extravascular compartment to the blood compartment. Interestingly, F(ab')(2) and Fab showed distinct efficiencies depending on their route of injection. F(ab')(2) induced a faster venom neutralization and redistribution than Fab when injected intravenously. Fab was more effective than F(ab')(2) by the intramuscular route. The hemodynamic effects of Aah venom were further investigated. Changes in mean arterial pressure and heart rate were observed in parallel with an upper airway obstruction. Fab was more effective than F(ab')(2) for preventing early symptoms of envenomation, whatever their route of administration. Intraperitoneal injection of F(ab')(2) and Fab was similar for the prevention of the delayed symptoms, even after a late administration. Fab was more effective than F(ab')(2) in the inhibition of airway resistance, independent of the route and time of administration. These results show that the treatment for scorpion stings might be improved by the intravascular injection of a mixture of Fab and F(ab')(2). If antivenom cannot be administered intravenously, Fab might be an alternative as they are more effective than F(ab')(2) when injected intramuscularly.
Research Interests: Pharmacology, Biology, Medicine, Optimization, Antibodies, and 15 moreAnimals, Male, Anesthesia, Heart rate, Heart, Antivenom, Rats, Envenomation, Airway Obstruction, Neutralization, Neutralization tests, Airway resistance, Mean Arterial Pressure, Antivenins, and Pharmacology and pharmaceutical sciences
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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)... more
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.