Abstract

BackgroundSnakes belonging to the Bothrops genus are vastly distributed in Central and South America and are responsible for most cases of reported snake bites in Latin America. The clinical manifestations of the envenomation caused by this genus are due to three major activities—proteolytic, hemorrhagic and coagulant—mediated by metalloproteinases, serine proteinases, phospholipases A2 and other toxic compounds present in snake venom. Interestingly, it was observed that snakes are resistant to the toxic effects of its own and other snake’s venoms. This natural immunity may occur due the absence of toxin target or the presence of molecules in the snake plasma able to neutralize such toxins.MethodsIn order to identify anti-venom molecules, we construct a cDNA library from the liver of B. jararaca snakes. Moreover, we analyzed the expression profile of four molecules—the already known anti-hemorrhagic factor Bj46a, one gamma-phospholipase A2 inhibitor, one inter-alpha inhibitor and one C1 plasma protease inhibitor—in the liver of juvenile and adult snakes by qPCR.ResultsThe results revealed a 30-fold increase of gamma-phospholipase A2 inhibitor and a minor increase of the inter-alpha inhibitor (5-fold) and of the C1 inhibitor (3-fold) in adults. However, the Bj46a factor seems to be equally transcribed in adults and juveniles.DiscussionThe results suggest the up-regulation of different inhibitors observed in the adult snakes might be a physiological adaptation to the recurrent contact with their own and even other snake’s venoms throughout its lifespan. This is the first comparative analysis of ontogenetic variation of expression profiles of plasmatic proteins with potential anti-venom activities of the venomous snake B. jararaca. Furthermore, the present data contributes to the understanding of the natural resistance described in these snakes.

Highlights

  • The genus Bothrops is widely distributed in Central and South America, being the most common genus reported in ophidian accidents (Cidade et al, 2006)

  • Transcripts encondig to metalloprotease inhibitors were found in our cDNA library of B. jararaca liver Data S1, including the anti-hemorrhagic factor BJ46a, which presents inhibitory activity against venom metalloproteases

  • Quantitative analyses obtained by Quantitative PCR (qPCR) using specific primers for BJ46a showed no significant differences between juvenile and adult B. jararaca snakes (Fig. 1A)

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Summary

Introduction

The genus Bothrops is widely distributed in Central and South America, being the most common genus reported in ophidian accidents (Cidade et al, 2006). Clinical manifestations of bothropic envenomation are due to the following venom activities: (1) proteolytic, resulting in inflammatory edema at the bite site; (2) hemorrhagic, related to endothelial damage and systemic bleeding; (3) coagulant, responsible for the consumption of coagulation factors and consequent homeostasis disruption; and (4) myonecrotic, related to permanent tissue loss, disability and amputation (Rosenfeld, 1971) These activities are mediated by a number of venom components, such as metalloproteinases, serine proteinases, phospholipases A2 (PLA2s), L-amino acid oxidases (LAAOs) and other toxic compounds (Fox et al, 2006; Zelanis et al, 2010). The results suggest the up-regulation of different inhibitors observed in the adult snakes might be a physiological adaptation to the recurrent contact with their own and even other snake’s venoms throughout its lifespan This is the first comparative analysis of ontogenetic variation of expression profiles of plasmatic proteins with potential anti-venom activities of the venomous snake B. jararaca. The present data contributes to the understanding of the natural resistance described in these snakes

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