The effects of the presence or absence of crotamine in rattlesnake venom

Lídia Jorge Tasima, MSc student, Interinstitutional Graduate Program in Biotechnology (Butantan Institute – IBU, University of São Paulo, USP, and Institute for Technological Research – IPT), São Paulo, SP, Brazil.

Daniela Miki Hatakeyama, PhD student, Interinstitutional Graduate Program in Biotechnology (Butantan Institute – IBU, University of São Paulo – USP, and Institute for Technological Research – IPT), and Laboratory of Herpetology, Butantan Institute, São Paulo, SP, Brazil.

Anita Mitico Tanaka-Azevedo, Scientific Researcher VI, Interinstitutional Graduate Program in Biotechnology (Butantan Institute – IBU, University of São Paulo, USP, and Institute for Technological Research – IPT), and Laboratory of Herpetology, Butantan Institute, São Paulo, SP, Brazil.

The article “Crotamine in Crotalus durissus: distribution according to subspecies and geographic origin, in captivity or nature”, published in the Journal of Venomous Animals and Toxins including Tropical Diseases (vol. 26) in the thematic series “Snake venoms: from production to bioprospecting”, analyzes the presence or absence of a protein in rattlesnake venom, known as crotamine. This protein is of great medical interest due to its ability to enter cells and its antitumoral and analgesic activities. Besides, other unexpected effects have been found for this protein, one of which is that animals treated with oral crotamine showed a reduction in weight gain when compared to animals of the control group. The variation in the presence or absence of this protein in rattlesnake venom was already known, thus we decided to check if it had any pattern, possible variations in the venom effects and the capacity of the antivenom to neutralize both types of venoms. This research, carried out at the Butantan Institute between 2016 and 2018, revealed that the presence of crotamine is related to the geographic distribution of snakes and their subspecies. In addition, our findings showed differences between pools relative to the abundance of some proteins in venom composition and time to death in the lethality assay.

This work was performed in the Laboratory of Herpetology of the Butantan Institute as an undergraduate research project by the student Lídia Jorge Tasima, supervised by Dr. Anita Mitico Tanaka Azevedo. For that, venoms were collected from more than 200 rattlesnakes, from different subspecies, localities, and from wild and captive snakes. Different methodologies were used to identify the presence of crotamine in the venom of these individuals, and then, after confirming which venoms contained crotamine, two pools were created, one with and other without crotamine, in order to verify if there would be differences in their protein composition and effects.

Rattlesnake (Crotalus durissus) specimen analyzed in the present study. Image: Sávio S. Sant’Anna, reproduced with permission.

The obtained results showed that, apparently, there is a tendency of certain subspecies to have more individuals with crotamine than others. However, a trend was also observed in relation to geographical distribution. Geographic distribution is a trait in the separation of subspecies, which could make this difference be due to geography. The presence of crotamine has already been associated with the presence of a gene, which facilitates the explanation of why some populations have more snakes with crotamine in their venom than others since it would be a characteristic inherited from the parents. Moreover, the difference in the abundance of some proteins in the venom composition could be related to the difference in time of death. Thus, the venom that did not contain crotamine killed faster. These differences between venoms can lead to ineffectiveness in treatment with antivenom. For the antivenom to be effective, it must be produced with the greatest possible variability of venoms, covering the largest number of proteins and variables. Therefore, this work highlights the importance of using venoms with and without crotamine in antivenom production.

The presence of crotamine is not the unique variation found in snake venoms. It is already known that snake venom can vary due to several characteristics, such as species, geographic distribution, age, among others. All these variations may affect the effectiveness of the antivenom. Bearing this in mind, our group seeks to study a wide variety of snake venoms from different groups, analyzing their variations and the effectiveness of antivenom, always pursuing the improvement of the effectiveness of antiophidic serum for the treatment of the most diverse number of medically important snakes in Brazil.

References

CESAR, E. “Os efeitos da crotamina no metabolismo”. Pesquisa Fapesp, Ed. 269, 2018. Available in: https://revistapesquisa.fapesp.br/os-efeitos-da-crotamina-no-metabolismo/. Accessed: November 30, 2020.

MARINOVIC, M. P. et al. Crotamine induces browning of adipose tissue and increases energy expenditure in mice. Scientific Reports [online]. 2018, vol. 446, no. 01, pp. 35-40 [viewed 30 November 2020]. https://doi.org/10.1016/j.gene.2009.05.015. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0378111909003229?via%3Dihub

OGUIURA, N. et al. Intraspecific variation of the crotamine and crotasin genes in Crotalus durissus rattlesnakes. Gene [online]. 2009, vol. 446, no.1, pp. 35-40 [viewed 30 November 2020]. https://doi.org/10.1016/j.gene.2009.05.015. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0378111909003229?via%3Dihub

To read the article, acess

TASIMA, L. J. et al. Crotamine in Crotalus durissus: distribution according to subspecies and geographic origin, in captivity or nature. J. Venom. Anim. Toxins incl. Trop. Dis [online]. 2020, vol. 26 [viewed 30 November 2020]. https://doi.org/10.1590/1678-9199-jvatitd-2019-0053. Available from: http://ref.scielo.org/r4qjkg

External links

Currículo Lattes – Anita Mitico Tanaka Azevedo: http://lattes.cnpq.br/1402209642648415

Currículo Lattes – Daniela Miki Hatakeyama: http://lattes.cnpq.br/1721697241622035

Currículo Lattes – Lídia Jorge Tasima: http://lattes.cnpq.br/0825480555035374

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