Another record of significant regional variation in toxicity of Tityus serrulatus venom in Brazil: A step towards understanding the possible role of sodium channel modulators

The scorpion Tityus serrulatus is responsible for the most severe accidents that have been registered in Brazil, mainly in the state of Minas Gerais (MG), being the lung edema (LE), the main cause of death in these accidents. Although an increased in the number of accidents caused to this species in Federal District (Distrito Federal - DF), it seems that this particular species is not responsible for severe scorpionism cases in this region. Given this observation, we tested the toxicity in mice and compared the ability of T. serrulatus venom from DF (Ts-DF) and Minas Gerais State (Ts-MG) to induce LE in rats. The LD50 of Ts-DF venom was 51.6 μg/mouse, almost twice (1.98) higher than that obtained for Ts-MG venom. The ability of venom (0.5 mg/kg) to induce LE in rats was determined by the wet weight differences between treated and untreated lungs, by pulmonary morphological analyses and by pulmonary vascular permeability (PVP) using the Evans blue protocol. Significant differences in the wet weight of lungs and changes in PVP were found in Ts-MG venom treated rats when compared to rats treated with Ts-DF venom or untreated rats (p < 0.001), but no differences occurred when comparing rats treated with Ts-DF venom and untreated rats (p < 0.05). These results were confirmed by evaluation of pulmonary morphology. Comparison of chromatographic profiles obtained from these venoms (Ts-DF and Ts-MG) using the fractal dimension (D) analysis and the molecular mass fingerprint of the chromatographic fractions showed a higher number of components between 35 and 40% acetonitrile in Ts-MG venom than in Ts-DF venom, indicating a higher diversity of sodium channel modulators in that venom.