Quantitative Characterization of the Hemorrhagic, Necrotic, Coagulation-Altering Properties and Edema-Forming Effects of Zebra Snake (<i>Naja nigricincta nigricincta</i>) Venom

Kandiwa, Erick; Mushonga, Borden; Samkange, Alaster; Fabiano, Ezequiel

doi:10.1155/2018/6940798

Cited by 10 publications

(13 citation statements)

References 40 publications

(43 reference statements)

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“…While the prothrombinase complex formation inhibition activity was 12 times stronger than that of the thrombin inhibition activity, the inhibition of thrombin would exhibit synergistic effects in combination with FXa inhibition due to the fact that the two enzymes are linked in the clotting cascade and would otherwise produce positive feedback loops that result in more clots. Local and systemic coagulation disturbances have been observed in victims envenomated by the African spitting cobra species Naja nigricincta , [21], and laboratory tests on N. nigricincta have confirmed the potenty ability to produce haemorrhage [22]. These haemorrhagic clinical observations and laboratory results are consistent with the anticoagulation results in this study.…”

Section: Discussionsupporting

confidence: 89%

Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)

Bittenbinder

Zdenek

Brouw

et al. 2018

Toxins

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Snakebite is a global tropical disease that has long had huge implications for human health and well-being. Despite its long-standing medical importance, it has been the most neglected of tropical diseases. Reflective of this is that many aspects of the pathology have been underinvestigated. Snakebite by species in the Elapidae family is typically characterised by neurotoxic effects that result in flaccid paralysis. Thus, while clinically significant disturbances to the coagulation cascade have been reported, the bulk of the research to date has focused upon neurotoxins. In order to fill the knowledge gap regarding the coagulotoxic effects of elapid snake venoms, we screened 30 African and Asian venoms across eight genera using in vitro anticoagulant assays to determine the relative inhibition of the coagulation function of thrombin and the inhibition of the formation of the prothrombinase complex through competitive binding to a nonenzymatic site on Factor Xa (FXa), thereby preventing FXa from binding to Factor Va (FVa). It was revealed that African spitting cobras were the only species that were potent inhibitors of either clotting factor, but with Factor Xa inhibited at 12 times the levels of thrombin inhibition. This is consistent with at least one death on record due to hemorrhage following African spitting cobra envenomation. To determine the efficacy of antivenom in neutralising the anticoagulant venom effects, for the African spitting cobras we repeated the same 8-point dilution series with the addition of antivenom and observed the shift in the area under the curve, which revealed that the antivenom performed extremely poorly against the coagulotoxic venom effects of all species. However, additional tests with the phospholipase A2 inhibitor LY315920 (trade name: varespladib) demonstrated a powerful neutralisation action against the coagulotoxic actions of the African spitting cobra venoms. Our research has important implications for the clinical treatment of cobra snakebites and also sheds light on the molecular mechanisms involved in coagulotoxicity within Naja. As the most coagulotoxic species are also those that produce characteristic extreme local tissue damage, future research should investigate potential synergistic actions between anticoagulant toxins and cytotoxins.

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Section: Discussionsupporting

confidence: 89%

Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)

Bittenbinder

Zdenek

Brouw

et al. 2018

Toxins

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“…The venoms of the cobra snakes N. mossambica and N.n. nigricincta are known to possess cytotoxic activity to their victims [ 13 , 19 ]— N. nigricincta is also reported to possess haemorrhagic, anticoagulant, and thrombolyt activity in animals [ 13 ]. The present study aimed to characterise the venoms of these cobra snakes in order to identify the specific proteins present.…”

Section: Discussionmentioning

confidence: 99%

“…nigricincta is not considered in its preparation [ 18 , 43 ]. Another example of ineffective antivenin has been reported by Sintiprungrat et al [ 13 ], where the antivenin produced against the Indian N. naja was less effective against the Sri Lankan N. naja. The composition of the venom from these species has geographical intra-specific variations [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…The venoms were milked from each adult N. mossambica and N.n. nigricincta and were lyophilised, yielding 95.3 and 129.2 mg, respectively [ 13 ]. These crude venom samples were stored at −20 °C until experimentation.…”

Section: Methodsmentioning

confidence: 99%

“…To our knowledge, the venom composition N. n. nigricincta has not been characterised. However, in animals, the N. n. nigricincta venom has been reported to possess haemorrhagic, necrotic, procoagulant and thrombolytic activities [ 13 ]. The present study aimed to profile the venom composition of N. mossambica and N. n. nigricincta from Namibia.…”

Section: Introductionmentioning

confidence: 99%

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Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta

Katali

Shipingana

Nyarangó

et al. 2020

Toxins

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Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA2) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation.

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Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya

et al. 2022

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Quantitative Characterization of the Hemorrhagic, Necrotic, Coagulation-Altering Properties and Edema-Forming Effects of Zebra Snake (Naja nigricincta nigricincta) Venom

Cited by 10 publications

References 40 publications

Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)

Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)

Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta

Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya

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