Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection.

Arley Patiño,Juan Quintana,Dora Benjumea,José Gutiérrez,Jaime Pereañez,Alexandra Rucavado

doi:10.3390/toxins7051532

Arley Patiño, Juan Quintana + Show 4 more

Open Access

https://doi.org/10.3390/toxins7051532

Copy DOI

Abstract

Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.

Highlights

Envenomation by snakebites is a relevant public health issue in many regions of the world, in tropical and subtropical countries of Africa, Asia, Latin America and Oceania [1]
Both extracts totally inhibited the lethal activity of B. asper venom at 75 mg/kg
We evaluated the inhibition of venom-induced systemic hemorrhage by quantifying mg of hemoglobin/g of organ in homogenates of kidneys and heart after subcutaneous (s.c.) injection of venom and pretreatment with the extracts

Summary

Introduction

Envenomation by snakebites is a relevant public health issue in many regions of the world, in tropical and subtropical countries of Africa, Asia, Latin America and Oceania [1]. In the case of snakes of the family Viperidae, which inflict the vast majority of accidents in the Americas, the pathophysiology of envenomation includes both local and systemic manifestations associated with hemorrhage, necrosis, edema, hypovolemia, nephrotoxicity, coagulopathy and cardiovascular shock [2] This complex clinical picture is the result of the action of various venom components, predominantly proteinases metallo and serine proteinases, phospholipases A2, C-type lectin-like proteins, and other minor components [3]. Bothrops asper is responsible for 50%–80% of snakebites, and 60%–90% of deaths secondary to snakebites in Central America and northern South America [4] Envenoming by this species induces marked local tissue damage that includes pain, edema, hemorrhage, blisters, dermonecrosis and myonecrosis [4,5]. The clinical manifestations of systemic alterations induced by

Results

Discussion

Conclusion