Montivipera bornmuelleri venom has immunomodulatory effects mainly up-regulating pro-inflammatory cytokines in the spleens of mice

Yacoub, T; Rima, Mohamad; Sadek, Riyad; Hleihel, Walid; Fajloun, Ziad; Karam, Marc

doi:10.1016/j.toxrep.2018.02.011

Cited by 21 publications

(20 citation statements)

References 27 publications

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“…Different biological activities of Montivipera bornmuelleri's venom have been recently described (for review, see Rima et al, 2018). Among these, the selective cytotoxicity of M. bornmuelleri's venom on benign and malignant cells (Sawan et al, 2017) and its upregulation of pro-inflammatory cytokines (Yacoub et al, 2018) suggested an anticancer potential of the venom. To further validate this hypothesis, this study was conducted to dissect the cytotoxicity of M. bornmuelleri's crude venom on cancer cell lines and its effect on tumor growth in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…To further validate this hypothesis, this study was conducted to dissect the cytotoxicity of M. bornmuelleri's crude venom on cancer cell lines and its effect on tumor growth in vivo. We started our experimental approach by checking whether the impact of M. bornmuelleri's venom on pro-inflammatory cytokines levels described previously (Yacoub et al, 2018) is due to endotoxins within the venom. In fact, endotoxins are found on the outer membrane of most gram-negative bacteria (Raetz, 1990) and are known as strong inducers of the immune system (Singh & Jiang, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Later on, another study investigated M. bornmuelleri ’s venom effect on pro-inflammatory cytokines in vivo. Interestingly, while pro-inflammatory and anti-tumor cytokines (INF-γ, TNF-α, IL-1β, IL-4, IL-17) were up-regulated, anti-inflammatory cytokine (IL-10) was down-regulated in mice injected with the venom, suggesting an immunomodulatory effect of the venom ( Yacoub et al, 2018 ). These findings suggest an anticancer potential of M. bornmuelleri ’s venom that is worth further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

Haddoub

Rima

Heurtebise

et al. 2020

PeerJ

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Background Montivipera bornmuelleri’s venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri’s venom and its effect on tumor growth in vivo. Methods The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection. Results The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri’s venom in vitro which, however, does not translate to an anticancer action in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

Haddoub

Rima

Heurtebise

et al. 2020

PeerJ

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“…Despite the low number of studies on the characterization of the inflammatory process involved in the snake envenomation of the Viperinae subfamily, which includes the genus Bitis, a recent work was published showing the pro-inflammatory activity of the Montivipera bornmuelleri venom using a peritonitis mice model. After 6 h and 24 h of venom inoculation, the production of TNF-α, IFN-γ, IL-1β, IL-17, IL-4 and IL-10 were detected [25]. In another study, after treating U937 cells with Vipera ammodytes ammodytes venom, an increase in the expression of several inflammatory genes was observed, such as IL-1β and IL-8 [26].…”

Section: Introductionmentioning

confidence: 93%

Bitis arietans Snake Venom Induces an Inflammatory Response Which Is Partially Dependent on Lipid Mediators

Megale

Portaro

Silva

2020

Toxins

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Bitis arietans is a snake of medical importance, as it is responsible for more accidents in humans and domestic animals than all other African snakes put together. The accidents are characterized by local and systemic alterations, such as inflammation, cardiovascular and hemostatic disturbances, which can lead victims to death or permanent disability. However, little is known about the envenomation mechanism, especially regarding the inflammatory response, which is related to severe clinical conditions triggered by the venom. Therefore, the aim of the present study was to evaluate the inflammatory response related to the B. arietans envenomation using a peritonitis mice model. By pharmacological interventions and use of mice genetically deficient of the 5-lipoxygenase enzyme (5-LO−/−) or platelet-activating factor (PAF) receptor (PAFR−/− the participation of eicosanoids and PAF in this response was also investigated. The obtained results demonstrated that the venom induces an in vivo inflammatory response, characterized by an early increased vascular permeability, followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity, accompanied by the production of the eicosanoids LTB4, LTC4, TXB2 and PGE2, as well as the local and systemic production of IL-6 and MCP-1. These inflammatory events were attenuated by the pre-treatment with anti-inflammatory drugs that interfere in lipid mediators’ functions. However, 5-LO−/− mice did not show a reduction of inflammatory response induced by the venom, while PAFR−/− mice showed a reduction in both the PMN leukocytes number and the local and systemic production of IL-6 and MCP-1. This study demonstrated that the Bitis arietans venom contains toxins that trigger an inflammatory process, which is partially dependent on lipid mediators, and may contribute to the envenomation pathology.

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“…These experiments are now feasible since the toxicity of the venom has been recently identified in vivo [ 62 ]. More recently, the immunomodulatory effects of M. bornmuelleri venom in vivo on the splenic levels of tumor necrosis factor, TNF-α; Interferon IFN-γ; and Interleukins, IL-4, IL-10, IL-1β, and IL-17 have been studied in vivo [ 63 ]. In fact, M. bornmuelleri venom up-regulated the levels of the pro-inflammatory cytokines, TNF-α, IFN-γ, IL-1β, and IL-17, and established a trend in decreasing the anti-inflammatory cytokine, IL-10.…”

Section: Montivipera Bornmuellerimentioning

confidence: 99%

Vipers of the Middle East: A Rich Source of Bioactive Molecules

et al. 2018

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Snake venom serves as a tool of defense against threat and helps in prey digestion. It consists of a mixture of enzymes, such as phospholipase A2, metalloproteases, and l-amino acid oxidase, and toxins, including neurotoxins and cytotoxins. Beside their toxicity, venom components possess many pharmacological effects and have been used to design drugs and as biomarkers of diseases. Viperidae is one family of venomous snakes that is found nearly worldwide. However, three main vipers exist in the Middle Eastern region: Montivipera bornmuelleri, Macrovipera lebetina, and Vipera (Daboia) palaestinae. The venoms of these vipers have been the subject of many studies and are considered as a promising source of bioactive molecules. In this review, we present an overview of these three vipers, with a special focus on their venom composition as well as their biological activities, and we discuss further frameworks for the exploration of each venom.

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Montivipera bornmuelleri venom has immunomodulatory effects mainly up-regulating pro-inflammatory cytokines in the spleens of mice

Abstract: Graphical abstract

Cited by 21 publications

References 27 publications

Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

Bitis arietans Snake Venom Induces an Inflammatory Response Which Is Partially Dependent on Lipid Mediators

Vipers of the Middle East: A Rich Source of Bioactive Molecules

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