Neuro- and Cardiovascular Activities of Montivipera bornmuelleri Snake Venom

Abstract

The complications following snake bite envenoming are due to the venom’s biological activities, which can act on different systems of the prey. These activities arise from the fact that snake venoms are rich in bioactive molecules, which are also of interest for designing drugs. The venom of Montivipera bornmuelleri, known as the Lebanon viper, has been shown to exert antibacterial, anticancer, and immunomodulatory effects. However, the venom’s activity on the nervous system has not yet been studied, and its effect on the cardiovascular system needs further investigation. Because zebrafish is a convenient model to study tissue alterations induced by toxic agents, we challenged it with the venom of Montivipera bornmuelleri. We show that this venom leads to developmental toxicity but not teratogenicity in zebrafish embryos. The venom also induces neurotoxic effects and disrupts the zebrafish cardiovascular system, leading to heartbeat rate reduction and hemorrhage. Our findings demonstrate the potential neurotoxicity and cardiotoxicity of M. bornmuelleri’s venom, suggesting a multitarget strategy during envenomation.

Venomous Bites, Stings and Poisoning by European Vertebrates as an Overlooked and Emerging Medical Problem: Recognition, Clinical Aspects and Therapeutic Management

“…Vipers of the genus Montivipera are mostly located in the Middle East, while in Europe they inhabit only few areas in northeastern Greece and some Aegean islands [ 25 , 26 , 28 ]. The genus Montivipera represents a higher medical threat in the eastern part of its range rather than in the European continent [ 55 , 56 , 57 , 58 ].…”

“…Erythema and edema arise in the bite site, followed by rapid spreading, extensive swelling, local ecchymosis, blistering and necrosis. Systemic symptoms, when present, include diffuse myalgias, anemia, coagulopathies and neurological and urological symptoms [ 55 , 56 , 57 , 58 ].…”

A Comparative Analysis of the Venom System between Two Morphotypes of the Sea Anemone Actinia equina

“…The complexity of venoms, which are mixtures of different compounds of which toxins are just a part, plus the variety of toxicological models render comparisons difficult. Nonetheless, a similar study with the zebrafish embryo model to test the toxicity of crude venom extracted from the snake Montivipera bornmuelleri , known as the Lebanon viper, yielded an LD 50 (24 h) of 62 μg/mL of total protein in the venom extract [ 32 ], which means that A. equina venoms may be more toxic to the model, given the distinction in the toxicity threshold by several orders of magnitude (0.25 and 0.61 for extracts from green and red morphotypes, respectively), despite the differential duration of the assays. In addition, although the toxicity of the viper venom was hitherto tested in chorionated embryos (as opposed to the dechorionated embryos used in the present study), the referred study gives the understanding that the extracts obtained from A. equina are substantially toxic.…”

Separation and Analytical Techniques Used in Snake Venomics: A Review Article

“…This model is used to monitor atrial and ventricular rates, blood flow and clot formation. Recently, we took advantage of zebrafish embryos transparency to assess the direct cardiotoxicity of SV [61]. In addition, the zebrafish model was used to isolate the cardiotoxic molecule from Lachesis muta venom.…”

“…This fraction was further purified using RP-HPLC, and the isolated protein was shown to inhibit indirectly stimulated twitches of sciatic nerve-muscle preparations [67]. Of note, SDS-PAGE is very useful in bioassay-guided fractionation, since it can indicate the protein content of each fraction eluted and the purity of the isolated protein [61]. Different combinations of separation techniques have been used for the isolation of novel SV molecules that upon biological characterization implicate the clinical outcome of the toxins or their potential use for drug development.…”