Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay

Abstract

Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO) recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD50 determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD50 results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase chromatographic profiles also has a potential application in venoms’ quality control, as there were fewer neurotoxins detected in the venom with high LD50 value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD50 assay to evaluate the venom excellence by discriminating—and discarding—poor-quality batches, and, consequently, with a positive impact on the number of animals used. Notably, proposed assays are fast and inexpensive, being technically and economically feasible in Tityus serrulatus venom quality control to produce effective antivenoms.

Purification and Biochemical Characterization of TsMS 3 and TsMS 4: Neuropeptide-Degrading Metallopeptidases in the Tityus serrulatus Venom

“…Recently our group demonstrated that the T. serrulatus venom proteases are indicative of the venom’s toxicity, since venom batches with lower proteolytic activities over the FRET substrate showed higher LD 50 values, and therefore are less toxic in comparison to the batches with greater hydrolytic activities [43]. In this manner, metalloserrulases 3 and 4 may be important toxins from the venom, acting in the formation or inactivation of human neuropeptides, besides being responsible for the maturation of endogenous peptides [22].…”

Scorpion envenomation in Brazil: Current scenario and perspectives for containing an increasing health problem

“…The venom of T. stigmurus can have a lower experimental median lethal dose (LD 50 ) when compared to T. serrulatus and T. bahiensis, suggesting a higher toxicity of this venom [94]. However, as individual and populational differences in scorpion species venom composition have been reported [86][87][88]95], it is difficult to assess whether the reported difference in LD 50 values directly reflects the venom toxicity of each species. Factors as the time after the last extraction of the venom, types of prey present in the diet, and different processing techniques can alter venom composition and toxicity [88,96,97].…”