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Toxins 2017, 9(12), 380; https://doi.org/10.3390/toxins9120380

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

1
Immunochemistry Laboratory, Butantan Institute, CEP 05503-900 São Paulo, Brazil
2
Analytical Development Laboratory, Butantan Institute, CEP 05503-900 São Paulo, Brazil
3
Mass Spectrometry Laboratory, Brazilian Biosciences National Laboratory, CEP 13083-970 LNBio, Brazil
These authors contributed equally to this study.
*
Authors to whom correspondence should be addressed.
Academic Editor: Elisabeth Ferroni Schwartz
Received: 22 October 2017 / Revised: 10 November 2017 / Accepted: 17 November 2017 / Published: 23 November 2017
(This article belongs to the Special Issue Scorpion Toxins)
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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. View Full-Text
Keywords: Tityus serrulatus; venom quality; toxicity; proteases; RP-HPLC; in vitro assays; median lethal dose Tityus serrulatus; venom quality; toxicity; proteases; RP-HPLC; in vitro assays; median lethal dose
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Cajado-Carvalho, D.; Galvão, J.; Kuniyoshi, A.K.; Carneiro, P.S.; Paes Leme, A.F.; Pauletti, B.A.; Marengo, E.B.; Portaro, F.V. Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay. Toxins 2017, 9, 380.

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