Capillary leak syndrome induced by the venoms of Russell's Vipers (Daboia russelii and Daboia siamensis) from eight locales and neutralization of the differential toxicity by three snake antivenoms

Lingam, Thava Malar Changra; Tan, Kae Yi; Tan, Choo Hock

doi:10.1016/j.cbpc.2021.109186

Cited by 6 publications

(6 citation statements)

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“…In a proteopeptidome characterization of Bothrops jararaca venom, snake venom NCB was speculated to induce excitotoxicity and cause transient disorientation in prey, thus facilitating predation [ 116 ]. VEGF is found in some viperid venoms, notably from Russell’s Viper ( Daboia russelii and D. siamensis ) [ 58 , 117 ], and its function has been linked to the increment of vascular permeability, the underlying mechanism of capillary leak syndrome [ 118 , 119 ], which is uncommon in C. rhodostoma envenoming. The transcriptomic finding of 3FTXs, which are canonical toxins almost exclusive to elapid snakes, is puzzling but not totally unexpected, as some studies have also reported the detection of 3FTx transcripts in the venom glands of crotalid and colubrid snakes [ 120 , 121 ].…”

Section: Resultsmentioning

confidence: 99%

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan

et al. 2023

Toxins

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In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study de novo assembled and analyzed the venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM, Fragments Per Kilobase Million), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI > PII > PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensin-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%), and others (1.78%). The expressions of SVMP, CTL, and SVSP correlate with hemorrhagic, anti-platelet, and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) acts by inhibiting platelet aggregation. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitors), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (an ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

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Section: Resultsmentioning

confidence: 99%

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan

et al. 2023

Toxins

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“…In a proteopeptidome characterization of Bothrops jararaca venom, snake venom NCB was speculated to induce excitotoxicity and cause transient disorientation in prey, thus facilitating predation [111]. VEGF is found in some viperid venoms, notably from Russell's Viper (Daboia russelii and D. siamensis) [54,112], and its function has been linked to the increment of vascular permeability, the underlying mechanism of capillary leak syndrome [113,114] which is uncommon in C. rhodostoma envenoming. The transcriptomic finding of three-finger toxins (3FTx), which are canonical of and almost exclusive to elapid snakes, is puzzling but not totally unexpected, as several authors have also reported the detection of 3FTx transcripts in the venom glands of pit vipers and colubrid snakes [115,116].…”

Section: Toxins Detected Exclusively In Venom Gland Transcriptomementioning

confidence: 99%

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

Tan¹,

Tan²,

Ng³

et al. 2023

Preprint

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In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study assembled and analyzed the de novo venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI&gt;PII&gt;PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensinogen-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%) and others (1.78%). The expressions of SVMP, CTL and SVSP correlate with hemorrhagic, anti-platelet and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) is platelet-inhibitory. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitor), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

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“…Both display high levels of snake venom serine proteases (SVSP) (18.07% and 22.41%, respectively) and phospholipase A 2 (PLA 2 ) toxins (37.92% and 48.37%, respectively) despite their geographical separation [ 16 ]. Both Thai and Indonesian D. siamensis venoms are procoagulant in citrated human plasma [ 15 ] and can induce capillary leakage in mice [ 17 ]. However, the neuro-myotoxic effects of Indonesian and even Thai D. siamensis venom is less well defined than for some of the other geographical variants.…”

Section: Introductionmentioning

confidence: 99%

“…This is certainly the case for Indonesian D. siamensis since the pharmacology of this venom has not been studied in detail. In contrast, the venoms of Sri Lankan D. russelii [ 8 , 17 , 19 , 20 ] and D. siamensis from China [ 21 , 22 , 23 ] and Thailand [ 15 , 16 , 18 , 23 ] have been more well studied.…”

Section: Introductionmentioning

confidence: 99%

“…Whilst D. siamensis monovalent antivenom from Thailand has been recommended for use against the venom of Indonesian D. siamensis , challenges with availability and access to this specific antivenom persist. Previously, Thai antivenoms raised against multiple species have been proven to be experimentally efficacious and clinically effective [ 15 , 16 , 17 , 28 , 29 ]. However, antivenoms need to be administered to snakebite patients as early as possible to increase their effectiveness [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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A Comparison of the Efficacy of Antivenoms and Varespladib against the In Vitro Pre-Synaptic Neurotoxicity of Thai and Javanese Russell’s Viper (Daboia spp.) Venoms

Lay,

Hodgson

2024

Toxins

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The heterogeneity in venom composition and potency in disparate Eastern Russell’s viper (Daboia siamensis) populations has repercussions for the efficacy of antivenoms. This is particularly pronounced in geographical areas in which the venom of the local species has not been well studied and locally produced antivenoms are unavailable. In such cases, alternative therapies following envenoming, which are not limited by species specificity, may be employed to complement antivenoms. We studied the neuromuscular activity of D. siamensis venom from Thailand and Java (Indonesia) and the ability of Thai antivenoms and/or Varespladib to prevent or reverse these effects. Both Thai and Javanese D. siamensis venoms displayed potent pre-synaptic neurotoxicity but weak myotoxicity in the chick biventer cervicis nerve–muscle preparation. Whilst the neurotoxicity induced by both venoms was abolished by the prior administration of Thai D. siamensis monovalent antivenom or pre-incubation with Varespladib, Thai neuro-polyvalent antivenom only produced partial protection when added prior to venom. Pre-synaptic neurotoxicity was not reversed by the post-venom addition of either antivenom 30 or 60 min after either venom. Varespladib, when added 60 min after venom, prevented further inhibition of indirect twitches. However, the subsequent addition of additional concentrations of Varespladib did not result in further recovery from neurotoxicity. The combination of Thai monovalent antivenom and Varespladib, added 60 min after venom, resulted in additional recovery of twitches caused by either Thai or Javanese venoms compared with antivenom alone. In conclusion, we have shown that Varespladib can prevent and partially reverse the pre-synaptic neurotoxicity induced by either Thai or Javanese D. siamensis venoms. The efficacy of Thai D. siamensis monovalent antivenom in reversing pre-synaptic neurotoxicity was significantly enhanced by its co-administration with Varespladib. Further work is required to establish the efficacy of Varespladib as a primary or adjunct therapy in human envenoming.

show abstract

Capillary leak syndrome induced by the venoms of Russell's Vipers (Daboia russelii and Daboia siamensis) from eight locales and neutralization of the differential toxicity by three snake antivenoms

Cited by 6 publications

References 26 publications

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

De Novo Venom Gland Transcriptome Assembly and Characterization for Calloselasma rhodostoma (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

<em>De Novo </em>Venom Gland Transcriptome Assembly and Characterization for <em>Calloselasma rhodostoma</em> (Kuhl, 1824), the Malayan Pit Viper from Malaysia: Unravelling Toxin Gene Diversity in a Medically Important Basal Crotaline

A Comparison of the Efficacy of Antivenoms and Varespladib against the In Vitro Pre-Synaptic Neurotoxicity of Thai and Javanese Russell’s Viper (Daboia spp.) Venoms

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