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Archivos Venezolanos de Farmacología y Terapéutica

versión impresa ISSN 0798-0264

Resumen

TREJO, E et al. Tityus zulianus and Tityus discrepans venoms induced massive autonomic stimulation in mice. AVFT [online]. 2012, vol.31, n.1, pp.1-6. ISSN 0798-0264.

Venezuelan scorpion envenomation is a public health problem produced by Tityus discrepans (TD) and Tityus zulianus (TZ) species. Patients-en- venomend by TD developed gastrointestinal and pancreatic disorders and scorpion accidents involving TZ are associated with high mortality rate, which showed cardiopulmonary clinical disorders may be associated to the high levels of plasma catecholamines levels. This distinctive clinical output seems to be associated to a toxin repertoire diversity, which has been previously demonstrated. Trying to mimic the human-envenomation, some toxinological studies have been performed using TD and TZ ven- oms in several biomodels such as mice and anesthetized rams. The pur- pose of this study was to evaluate, in vivo using biomodels (mice), the role of autonomic nervous system (sympathetic) stimulation producing some of the clinical signs, via the catecholamines release, on the patho-physi- ology of the TZ and TD induced envenomation. Thus, a clinical signs here reported during a period of 1 hr, after a single intra-peritoneal injection of sub-lethal doses of TZ or TD venom, which are related with diarrhea, diaphoresis, intense salivation, dehydratation, dyspnea and spasticity in hind limbs. However, these animals did not exhibit vomiting, which is the most frequent human-envenomed TD patients. All animals inoculated with (TD or TZ) venoms developed diarrhea being more pronounced in TD group. Diaphoresis, sialorrhea and dehydratation were mainly observed in TD group. Dyspnea and the hind limb spasticity were only developed in TZ mice. These clinical manifestations (diarrhea, sialorrhea, dehydra- tation and intense salivation) are related to an activation of autonomic nervous system, via an intense release of their related neurotransmitters. Thus, autonomic stimulation (sympathetic) was evaluated following the catecholamine (Nor-Epinephrine)(NE) plasma levels in a function of en- venomation time. We found a significant increments at 1 hr, after venom injection, in more than 640% in NE plasma levels for TZ venom while in TD group, around 520% rise in NE concentrations were detected. This mas- sive rise in NE concentrations in TZ and TD-envenomed mice decreased at 6 hrs but remained higher until 24 hrs for both venoms in comparison with Control animals. However, these catecholamines plasma alterations do not explain the dyspnea and hind limb spasticity and more toxinologi- cal research should be done to understand the molecular mechanisms related to last clinical signs. Abbreviations: TD: Tityus discrepans, TTX: Tetrodotoxin, TZ: Tityus zu- lianus, NE, Nor-epinephrine, RyRs: Ryanodine receptors, IpTxA: impera- toxin A, ROS: reactive oxygen species, nAChR: nicotinic acetylcholine receptor (Na+ channel), (Nav): voltage-dependent sodium channel, MCa: maurocalcine, Tz1: < - toxin from Tityus zulianus.

Palabras clave : Nor-epinephrine; cathecholamine release; Tityus zulianus; Tityus discrepans; scorpion venoms.

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