Kn-Ba: a novel serine protease isolated from Bitis arietans snake venom with fibrinogenolytic and kinin-releasing activities

Megale, Ângela Alice Amadeu; Magnoli, Fábio Carlos; Kuniyoshi, Alexandre Kazuo; Iwai, Leo Kei; Tambourgi, Denise V.; Portaro, Fernanda Calheta Vieira; Silva, Wilmar Dias da

doi:10.1186/s40409-018-0176-5

Cited by 16 publications

(17 citation statements)

References 62 publications

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“…The question then arises of whether using a larger dose of D. siamensis venom can induce coagulopathies in the rabbit model, which requires further investigation. PLA 2 toxins in D. siamensis venom is believed to play a role as a specific antihypertensive component through its effects on releases of thromboxane A 2 (TXA 2 ) [49], prostacyclin (PGI) [44], autacoids such as histamine [38], kinin [50], and interaction with platelets and leukocytes. However, it has been demonstrated that histamine does not appear to play a role in D. russelii venom-induced vasorelaxation in comparison to the presence of the histamine H1 receptor antagonist [38].…”

Section: Comparative Venomics and Cardiovascular Effectsmentioning

confidence: 99%

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell’s viper ( Daboia siamensis ): correlation with renal pathophysiology in experimental rabbits

Chaiyabutr¹,

Chanhome²,

Vasaruchapong³

et al. 2022

J. Venom. Anim. Toxins incl. Trop.

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Background: Eastern Russell's viper (Daboia siamensis) is one of the most medically significant snakes responsible for the development of acute renal failure. However, variation of the clinical picture and renal pathophysiology following bites by young and adult D. siamensis have not been elucidated. Methods: In this study, we analyzed the venomic profiles of D. siamensis at different maturation stages of juvenile, subadult and adult groups. The same pooled venom from each group was subjected to enzymatic, electrophoretic and proteomic analysis, including sublethal toxicity (0.1 mg/kg iv.) examined on bodily functions by comparing the venom compositional and functional profiles among venom specimens from juvenile, subadult and adult D. siamensis by correlating them with the renal pathophysiology in experimental rabbits. Results:The comparative studies revealed that juvenile venom possessed higher phospholipase A 2 , metalloproteinase and serine proteinase levels, while subadult and adult venoms contained more L-amino acid oxidase, phosphodiesterase, the Kunitz-type serine protease inhibitor, disintegrin families and endothelial growth factor. An in vivo study revealed that the adult and subadult venoms caused persistent hypotension and bradycardia, while thrombocytopenia was a more characteristic effect of juvenile venom. All venom age groups showed significant reductions in renal hemodynamics and electrolyte excretions. The juvenile venom caused a higher tubulonephrosis lesion score than adult and subadult venoms. Conclusions: The D. siamensis venom shows an ontogenetic shift in its compositions and activities. Renal function alterations after envenomation depend on either the synergistic actions of different venom components or the disproportionate expression between the concentrations of enzymatic and non-enzymatic proteins in each age venom group. The high proportion of enzymatic toxin proteins in the juvenile venom results in greater nephrotoxicity.

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Section: Comparative Venomics and Cardiovascular Effectsmentioning

confidence: 99%

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell’s viper ( Daboia siamensis ): correlation with renal pathophysiology in experimental rabbits

Chaiyabutr¹,

Chanhome²,

Vasaruchapong³

et al. 2022

J. Venom. Anim. Toxins incl. Trop.

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“…The experimental models here used, and the results obtained, may be useful to understand the role of inflammation in BaV envenomation, hence potentially improving the victim's treatment, in addition to indicating the possible toxins responsible for these symptoms. In this sense, Kn-Ba, a serine protease with fibrinolytic and kinin-releasing activity, was isolated from the Bitis arietans venom [43] and it is also related to the inflammatory process, including the activation of the inflammasome complex and the release of active IL -1β. For this, new studies are being finalized.…”

Section: Discussionmentioning

confidence: 99%

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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“…Kn-Ba was purified from BaV as previously described [25]. Purified Kn-Ba was diluted in sterile PBS pH 7.2 and stored at −80 • C.…”

Section: Kn-bamentioning

confidence: 99%

“…Kn-Ba is also recognized by antibodies (Abs) present in the horse-serum anti-Bitis spp. venoms [25].…”

Section: Introductionmentioning

confidence: 99%

Bitis arietans Snake Venom and Kn-Ba, a Snake Venom Serine Protease, Induce the Production of Inflammatory Mediators in THP-1 Macrophages

Megale

Magnoli

Guidolin

et al. 2021

Toxins

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Bitis arietans is a snake of medical importance found throughout sub-Saharan Africa and in savannas and pastures of Morocco and western Arabia. The effects of its venom are characterized by local and systemic alterations, such as inflammation and cardiovascular and hemostatic disturbances, which can lead to victims’ death or permanent disability. To better characterize the inflammatory process induced by this snake’s venom, the participation of eicosanoids and PAF (platelet- activating factor) in this response were demonstrated in a previous study. In addition, edema and early increased vascular permeability followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity were accompanied by the production of the eicosanoids LTB4, LTC4, TXB2, and PGE2, and local and systemic production of IL-6 and MCP-1. In this context, the present study focused on the identification of inflammatory mediators produced by human macrophages derived from THP-1 cells in response to Bitis arietans venom (BaV), and Kn-Ba, a serine protease purified from this venom. Here, we show that Kn-Ba, and even the less intensive BaV, induced the production of the cytokine TNF and the chemokines RANTES and IL-8. Only Kn-Ba was able to induce the production of IL-6, MCP-1, and IP-10, whereas PGE2 was produced only in response to BaV. Finally, the release of IL-1β in culture supernatants suggests the activation of the inflammasomes by the venom of Bitis arietans and by Kn-Ba, which will be investigated in more detail in future studies.

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Kn-Ba: a novel serine protease isolated from Bitis arietans snake venom with fibrinogenolytic and kinin-releasing activities

Cited by 16 publications

References 62 publications

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell’s viper ( Daboia siamensis ): correlation with renal pathophysiology in experimental rabbits

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell’s viper ( Daboia siamensis ): correlation with renal pathophysiology in experimental rabbits

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

Bitis arietans Snake Venom and Kn-Ba, a Snake Venom Serine Protease, Induce the Production of Inflammatory Mediators in THP-1 Macrophages

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