Montivipera bornmuelleri venom selectively exhibits high cytotoxic effects on keratinocytes cancer cell lines.

CONTEXT: The Viperidae family venom is a rich source of bioactive compounds such as many proteases, which cause tissue necrosis and affect mostly the vascular system. However, the venom exhibits therapeutic potentials and has contributed to the development of some medical drugs. Specifically, the Montivipera bornmuelleri venom has shown to exhibit antibacterial, pro-inflammatory and antifungal activities. OBJECTIVE: This work evaluates the cytotoxic effect of the M. bornmuelleri venom on human-derived keratinocytes including the non-tumorigenic HaCaT, the benign A5 and the low-grade malignant II4 cells. MATERIALS AND METHODS: The toxicity of different venom concentrations (0.9, 1.87, 3.75, 7.5, 15, 30 and 60µg/mL) and their effect on the viability of the cells lines were assessed using the Lactate Dehydrogenase (LDH) activity and the Trypan blue tests after 24h of incubation. RESULTS: The venom was able to reduce the viability of all cell lines in a dose dependent manner with the HaCat cells being the least affected. For example, the 60µg/mL dose induced a more significant decrease the viability of A5 (44%) and II4 (21.33%) keratinocytes as compared to HaCaT cells (70.63%). Also, this venom showed a higher cytotoxic activity on the A5 (52.45%) and II4 (98.67%) cells as compared to HaCaT cells (30.14%) with an IC50 estimated at 10µg/mL on II4 and at 60µg/mL on benign A5. DISCUSSION AND CONCLUSION: Those differential cytotoxic effects of the M. bornmuelleri venom pave the road for more advanced studies which might unravel the potential anticancer effects of this venom.

The relaxant effect of the Montivipera bornmuelleri snake venom on vascular contractility.

Molecular richness of snake venoms is an important source of proteins and toxins with potent effects on the cardiovascular system. The alteration of the vascular system in the victim after a venomous snake bite is usually expressed by a significant decrease in blood pressure. Therefore, exploring snake venom to extract and characterize its biomolecules is of considerable medical interest, and formed the basis of this study. We assessed the potential of the venom of Montivipera bornmuelleri, a viper from Lebanon, to induce relaxant effect on isolated Wistar rat aorta via several mechanisms of action. The overall hypotensive effect of Montivipera bornmuelleri venom results from its synergetic action on different channels for the reduction of blood pressure. By actions of its metalloproteinases and phospholipase A2, the venom may induce the production of nitric oxide acting accordingly a vasodilator effect. It could act on the voltage-dependent potassium channels and/or the L-type calcium channels, inhibiting angiotensin converting enzyme and/or inhibiting the α1-adrenoceptors. This work demonstrates vasorelaxant effect of the Montivipera bornmuelleri venom acting on different pathways, reducing blood pressure.

Protein content analysis and antimicrobial activity of the crude venom of Montivipera bornmuelleri; a viper from Lebanon.

Viperidae snakes venoms represent a source of efficient bioactive components that have already led to the development of several new drugs. In this work, we analyzed the protein content of the Montivipera bornmuelleri crude venom using LC-ESI-MS, sephadex G-75 gel filtration and SDS-PAGE and demonstrated the presence of proteins with molecular masses corresponding to metalloprotease III, serine-protease and PLA2 in three fractions collected after gel filtration. Equally, we examined the antimicrobial effect of the venom that showed an important potency, as bactericidal agent, based on MBC and MIC values obtained, against Staphylococcus aureus and Morganella morganii bacteria. However, no activity was registered against Enterococcus faecalis, being the most resistant bacteria, neither against Aspergillus flavus and Penicillium digitatum fungal. Furthermore, on eleven other bacterial strains and the Candida albicans fungus, the venom has shown an intermediate efficacy by slightly reducing the growth. Our data concerning the Montivipera bornmuelleri venom give evidence of a rich and complex content aiding the exploration of new bioactive molecules for biopharmaceuticals purposes.

Identification of L-amino acid oxidase (Mb-LAAO) with antibacterial activity in the venom of Montivipera bornmuelleri, a viper from Lebanon.

The L-amino acid oxidase (LAAO) is a multifunctional enzyme, able to partake in different activities including antibacterial activity. In this study, a novel LAAO (Mb-LAAO) was isolated from the venom of M. bornmuelleri snake using size exclusion chromatography followed by RP-HPLC and partially characterized. However, the molecular weight of the Mb-LAAO determined by ESI-MS and SDS-PAGE was 59 960.4 Da. Once the enzymatic activity test confirming the enzyme's identity (transformation of L-leucine) was done, the Mb-LAAO was evaluated for its antibacterial activity against Gram-negative bacteria. It showed a remarkable effect against M. morganii and K. pneumoniae. Moreover, no cytotoxic activity was observed for Mb-LAAO against human erythrocytes arguing for an exploration of its pharmaceutical interest.