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Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom

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Abstract

Bot III neurotoxin is the most lethal α neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective β1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the β1 adrenergic receptor seems to dominate the β2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation.

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Abbreviations

Ach:

Acetyl-choline

Bot III toxin:

Neurotoxin purified from Buthus occitanus tunetanus scorpion venom

mAch-R:

Muscarinic receptor

nAch-R:

Nicotinic receptor

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Authors and Affiliations

  1. USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP 32, El–Alia Bab Ezzouar, 16111, Algiers, Algeria

    Imene Nakib & Fatima Laraba-Djebari

  2. Aix-Marseille University, CNRS UMR7290 CRN2M, IFR Jean-Roche, Université de la Méditerranée, Faculté de Médecine Nord, Bd Pierre Dramard, 13916, Marseille, Cedex 20, France

    Marie-France Martin-Eauclaire

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  1. Imene Nakib
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  2. Marie-France Martin-Eauclaire
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  3. Fatima Laraba-Djebari
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Correspondence to Fatima Laraba-Djebari.

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Nakib, I., Martin-Eauclaire, MF. & Laraba-Djebari, F. Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom. Inflammation 39, 1670–1680 (2016). https://doi.org/10.1007/s10753-016-0401-8

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