Efeitos da toxina TsTX-I isolada do veneno do escorpião Tityus serrulatus sobre o hipocampo de ratos

Abstract

Scorpion venoms are composed mainly by neurotoxins that are basic peptides with low molecular weight acting on ionic channels, mainly sodium channel, changing the release of chemical mediators. Crude venom of Tityus serrulatus scorpion, as well its toxins, has already been extensively studied. Many of the venom toxins were well characterized and sequenced. TsTX-I is one of the most important toxin present in the venom. This toxin acting by binding on site 4 of sodium channel, its peripherical effects have been well studied but its central effects are not well known. Some studies have been shown that scorpion toxins caused electrographic and behavioral effects in rats due to the release of neurotransmitters from central nervous system areas. Further, the toxins may change the levels of inflammatory mediators. These mediators also may cause convulsions in rats. Thus, the aim of the present work was verify if TsTX-I injection may change the level of chemical mediators mainly in amino acids neurotransmitters and cytokines and the integrity of neuronal cells. Cannulas and electrodes were implanted in the hippocampus of Wistar male rats by stereotaxic surgery. The electrographic record and behavioral analyze were made after toxin injection. A dose-response curve was constructed and then the dose used in the study was determined. The levels of neurotransmitters were determined in rats by microdialysis and HPLC. Cytokines were determined after toxin, kainic acid or saline by immunoenzymatic assays. For histological evaluation seven days after toxin injection animals were perfused the brain was removed, fixed, sliced and then stained for optical microscopy analyze of hippocampal CA1, CA3 and CA4 areas.The TsTX-I do not changed amino acids neutransmitters levels neither the number of intact neurons in the hippocampus. However it caused wete dog shakes, prostration, dyspnea and electrographic record changes. The toxin decreased IL-1β and IL-10 levels in the brain but do not caused significant alterations of the cytokines in the hippocampus. In conclusion, the hippocampal amino acids neurotransmitters did not participated of the effects of the toxin and there is no damage of hippocampal cells because glutamate, that causes toxicity, was not altered. It was also concluded that cytokines participated of the toxin effect. Although its site of action is in other brain regions, not in the hippocampus. It is possible that other neurotransmitters or cytokines in the brain are the responsible by the effects of the toxin.