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

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 LD determination as t...

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Bibliographic Details
Published in:Toxins 2017-11, Vol.9 (12), p.380
Main Authors: Cajado-Carvalho, Daniela, Galvão, Juliana, Kuniyoshi, Alexandre K, Carneiro, Patrícia Dos Santos, Paes Leme, Adriana Franco, Pauletti, Bianca Alves, Marengo, Eliana Blini, Portaro, Fernanda V
Format: Article
Language:English
Subjects:
Animals
Antivenom
Arthropod Proteins - analysis
Assaying
Biocompatibility
Biological Assay
Chromatography, Reverse-Phase
Electrophoresis, Polyacrylamide Gel
Ethics
Female
Hyaluronoglucosaminidase - metabolism
in vitro assays
In vitro methods and tests
In vivo methods and tests
Lethal dose
Lethal Dose 50
Male
Mass Spectrometry
Mass spectroscopy
median lethal dose
Neurotoxins
Nitrogen - analysis
proteases
Proteolysis
Quality control
RP-HPLC
Scorpion Venoms - chemistry
Scorpion Venoms - toxicity
Scorpions
Stings
Tityus serrulatus
Toxicity
Toxins
Venom
venom quality
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Summary: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 LD 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 LD results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for 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 LD value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD 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 venom quality control to produce effective antivenoms.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins9120380