Displaying publications 1 - 20 of 37 in total

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  1. David P, Lescure J, Savage JM, DAS I, Pauwels OSG, Vogel G, et al.
    Zootaxa, 2023 Jan 31;5231(3):331-339.
    PMID: 37045142 DOI: 10.11646/zootaxa.5231.3.8
    The purpose of this paper is to solve an overlooked nomenclatural problem involving two taxa of Colubridae, both described as Coluber korros. The first one is Coluber korros Schlegel, 1837, now Ptyas korros, a well-known and widespread species in south-east Asia. Its senior homonym is Coluber korros Lesson, 1831, a long forgotten taxon. Furthermore, these taxa are undoubtedly non-conspecific. We tentatively identify the holotype of this latter taxon as a large specimen of Coelognathus radiatus (F. Boie, 1827) and we specify its type locality as "Region of Kolkata, West Bengal State, eastern India" (the same specification of type-locality can hence be applied to the elapid Naja kaouthia Lesson, 1831). Nevertheless, following the strict principle of priority, Coluber korros Lesson, 1831 has priority over Coluber korros Schlegel, 1837. Based on the Code, we use Article 23.9 on reversal of precedence in order to preserve the use of the well-known taxon Coluber korros Schlegel, 1837 (now Ptyas korros) against its senior primary homonym Coluber korros Lesson, 1831. Finally, we consider Coluber boncorage Lesson, 1831 to be a nomen dubium.
    Matched MeSH terms: Elapidae
  2. Malih I, Ahmad rusmili MR, Tee TY, Saile R, Ghalim N, Othman I
    J Proteomics, 2014 Jan 16;96:240-52.
    PMID: 24269350 DOI: 10.1016/j.jprot.2013.11.012
    The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity.
    Matched MeSH terms: Elapidae/metabolism*
  3. REID HA, LIM KJ
    Br Med J, 1957 Nov 30;2(5056):1266-72.
    PMID: 13479694
    Matched MeSH terms: Elapidae*
  4. Fukuyama I, Vogel G, Matsui M, Eto K, Munir M, Hossman MY, et al.
    Zoolog Sci, 2020 Dec;37(6):586-594.
    PMID: 33269875 DOI: 10.2108/zs200100
    The red-bellied form of Calliophis intestinalis (Laurenti, 1768) sensu lato was originally reported from Pahang, west Malaysia. To determine the taxonomic status of this form, we examined the type specimens of Elaps sumatranus Lidth De Jeude, 1890, Calliophis intestinalis everetti (Boulenger, 1896), and Callophis furcatus var. nigrotaeniatus Peters, 1863. The results indicated that the red-bellied form of C. intestinalis should be named as Calliophis nigrotaeniatus comb. nov., whose valid species status was based on morphological and molecular analyses. We designate a lectotype and redescribe the species, which is genetically close to Calliophis bilineatus (Peters, 1881) from the Philippines, and is clearly distinguishable from other congeners by possessing a pair of gray or dark blue lateral stripes and by being bright red on the ventrum. Elaps sumatranus and C. i. everetti are relegated to subjective junior synonyms of C. nigrotaeniatus.
    Matched MeSH terms: Elapidae
  5. Wong KY, Tan CH, Tan NH
    Am J Trop Med Hyg, 2016 06 01;94(6):1392-9.
    PMID: 27022154 DOI: 10.4269/ajtmh.15-0871
    Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography-mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs.
    Matched MeSH terms: Elapidae*
  6. Tan CH, Tan KY, Lim SE, Tan NH
    J Proteomics, 2015 Aug 3;126:121-30.
    PMID: 26047715 DOI: 10.1016/j.jprot.2015.05.035
    The venom proteome of Hydrophis schistosus (syn: Enhydrina schistosa) captured in Malaysian waters was investigated using reverse-phase HPLC, SDS-PAGE and high-resolution liquid chromatography-tandem mass spectrometry. The findings revealed a minimalist profile with only 18 venom proteins. These proteins belong to 5 toxin families: three-finger toxin (3FTx), phospholipase A2 (PLA2), cysteine-rich secretory protein (CRISP), snake venom metalloprotease (SVMP) and L-amino acid oxidase (LAAO). The 3FTxs (3 short neurotoxins and 4 long neurotoxins) constitute 70.5% of total venom protein, 55.8% being short neurotoxins and 14.7% long neurotoxins. The PLA2 family consists of four basic (21.4%) and three acidic (6.1%) isoforms. The minor proteins include one CRISP (1.3%), two SVMPs (0.5%) and one LAAO (0.2%). This is the first report of the presence of long neurotoxins, CRISP and LAAO in H. schistosus venom. The neurotoxins and the basic PLA2 are highly lethal in mice with an intravenous median lethal dose of <0.2 μg/g. Cross-neutralization by heterologous elapid antivenoms (Naja kaouthia monovalent antivenom and Neuro polyvalent antivenom) was moderate against the long neurotoxin and basic PLA2, but weak against the short neurotoxin, indicating that the latter is the limiting factor to be overcome for improving the antivenom cross-neutralization efficacy.
    Matched MeSH terms: Elapidae/metabolism*
  7. Tan CH, Wong KY, Huang LK, Tan KY, Tan NH, Wu WG
    Toxins (Basel), 2022 Dec 07;14(12).
    PMID: 36548757 DOI: 10.3390/toxins14120860
    Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from South Africa. The major components in the venom are cytotoxins/cardiotoxins (~75.6% of total venom proteins) and alpha-neurotoxins (~7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A2 (PLA2) was undetected-this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.
    Matched MeSH terms: Elapidae/metabolism
  8. Tan CH, Tan KY, Fung SY, Tan NH
    BMC Genomics, 2015;16:687.
    PMID: 26358635 DOI: 10.1186/s12864-015-1828-2
    The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS.
    Matched MeSH terms: Elapidae/genetics*; Elapidae/metabolism*
  9. Modahl CM, Roointan A, Rogers J, Currier K, Mackessy SP
    PMID: 32194156 DOI: 10.1016/j.cbpc.2020.108743
    The genera Ophiophagus and Naja comprise part of a clade of snakes referred to as cobras, dangerously venomous front-fanged snakes in the family Elapidae responsible for significant human mortality and morbidity throughout Asia and Africa. We evaluated venom enzyme variation for eleven cobra species and three N. kaouthia populations using SDS-PAGE venom fingerprinting and numerous enzyme assays. Acetylcholinesterase and PLA2 activities were the most variable between species, and PLA2 activity was significantly different between Malaysian and Thailand N. kaouthia populations. Venom metalloproteinase activity was low and significantly different among most species, but levels were identical for N. kaouthia populations; minor variation in venom L-amino acid oxidase and phosphodiesterase activities were seen between cobra species. Naja siamensis venom lacked the α-fibrinogenolytic activity common to other cobra venoms. In addition, venom from N. siamensis had no detectable metalloproteinase activity and exhibited an SDS-PAGE profile with reduced abundance of higher mass proteins. Venom profiles from spitting cobras (N. siamensis, N. pallida, and N. mossambica) exhibited similar reductions in higher mass proteins, suggesting the evolution of venoms of reduced complexity and decreased enzymatic activity among spitting cobras. Generally, the venom proteomes of cobras show highly abundant three-finger toxin diversity, followed by large quantities of PLA2s. However, PLA2 bands and activity were very reduced for N. haje, N. annulifera and N. nivea. Venom compositionalenzy analysis provides insight into the evolution, diversification and distribution of different venom phenotypes that complements venomic data, and this information is critical for the development of effective antivenoms and snakebite treatment.
    Matched MeSH terms: Elapidae/classification; Elapidae/metabolism*
  10. Tan CH, Liew JL, Tan KY, Tan NH
    Toxicon, 2016 Oct;121:130-133.
    PMID: 27616455 DOI: 10.1016/j.toxicon.2016.09.003
    Venoms of Calliophis bivirgata and Calliophis intestinalis exhibited moderate binding activities toward Neuro Bivalent Antivenom (Taiwan) but not the other six elapid monovalent or bivalent antivenoms available in the region. All antivenoms failed to neutralize C. bivirgata venom lethality in mice. The findings indicate the need to validate antivenom cross-reactivity with in vivo cross-neutralization, and imply that distinct antigens of Calliophis venoms should be incorporated in the production of a pan-regional poly-specific antivenom.
    Matched MeSH terms: Elapidae
  11. Komaruddin SA, Mohamad NA, Fatihah-Syafiq M, Badli Sham BH, Mamat MA, Zakaria N
    Data Brief, 2020 Feb;28:104994.
    PMID: 32226800 DOI: 10.1016/j.dib.2019.104994
    This data article is about reptiles (lizard, snake, and skink) captured from fragmented forest within man-made lake of Tasik Kenyir that is situated in Terengganu State, Peninsular Malaysia. Data collection was conducted in January 2019 and sampling methods included drift fenced-pitfall traps and Visual Encounter Survey (VES). All animals were identified, measured snout to vent (SVL) and weighted before their release at the site of capture. The highlights like conservation statuses in the wild, detection type and substrate type are presented with the data to increase its value. A total of 73 individuals from 18 species, 15 generas and seven families of reptiles were recorded. The data comprised of seven reptile family groups Agamidae, Gekkonidae, Scincidae, Colubridae, Elapidae, Viperidae and Homalopsidae. Reptiles like Cyrtodactylus quadrivirgattus (n = 33, 45.2%) and Aphaniotis fusca (n = 7, 9.6%) were most dominant in the checklist and most of the animals were captured using VES. Data of SVL and mass of the animals can be further interpreted by researchers to assess the health condition of animals in the altered habitats.
    Matched MeSH terms: Elapidae
  12. Chan YW, Tan KY, Tan CH
    Toxicon, 2022 Dec;220:106942.
    PMID: 36240856 DOI: 10.1016/j.toxicon.2022.106942
    Snakebite envenoming is an important neglected tropical disease. Antivenom supply, however, remains limited in many parts of the world. This study aimed to examine the protein composition, immunoreactivity and neutralization efficacy of a new antivenom product (VINS Philippine Elapid Antivenoms, VPEAV) developed for the treatment of snakebite envenoming caused by the Philippine Cobra (Naja philippinensis), Samar Cobra (Naja samarensis) and King Cobra (Ophiophagus hannah). Size-exclusion chromatography, sodium-dodecyl sulfate-polyacrylamide gel electrophoresis and tandem mass spectrometry showed that VPEAV consisted of F(ab)'2 (∼90% of total antivenom proteins) with minimal protein impurities. Indirect ELISA showed varying immunoreactivity of VPEAV toward the different venoms (EC50 = 4-16 μg/ml), indicating distinct venom antigenicity between the species. In mice, the neutralization potency of VPEAV against the King Cobra venom was moderate (potency, P = 2.6 mg/ml, defined as the amount of venom completely neutralized per unit volume of antivenom). The potency was significantly lower against the N. philippinensis and N. samarensis venoms (P = 0.18-0.30 mg/ml), implying a higher dose may be needed for effective neutralization of the Naja venoms. Together, the findings suggest the potential and limitation of VPEAV in neutralizing the venom toxicity of the three Philippine elapid snakes.
    Matched MeSH terms: Elapidae
  13. Fung SY, Tan NH, Sim SM, Aguiyi JC
    PMID: 21785646 DOI: 10.1155/2012/486390
    Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.
    Matched MeSH terms: Elapidae
  14. Tan CH, Tan NH, Tan KY, Kwong KO
    Toxins (Basel), 2015 Feb;7(2):572-81.
    PMID: 25690691 DOI: 10.3390/toxins7020572
    Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.
    Matched MeSH terms: Elapidae*
  15. Yap MK, Tan NH, Sim SM, Fung SY, Tan CH
    PLoS Negl Trop Dis, 2014 Jun;8(6):e2890.
    PMID: 24901441 DOI: 10.1371/journal.pntd.0002890
    BACKGROUND: The optimization of snakebite management and the use of antivenom depend greatly on the knowledge of the venom's composition as well as its pharmacokinetics. To date, however, pharmacokinetic reports on cobra venoms and their toxins are still relatively limited. In the present study, we investigated the pharmacokinetics of Naja sumatrana (Equatorial spitting cobra) venom and its major toxins (phospholipase A2, neurotoxin and cardiotoxin), following intravenous and intramuscular administration into rabbits.

    PRINCIPAL FINDINGS: The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%) compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.

    CONCLUSION/SIGNIFICANCE: Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its role as the principal toxin in systemic envenoming.

    Matched MeSH terms: Elapidae*
  16. Mariam K, Tu AT
    J Nat Toxins, 2002 Dec;11(4):393-8.
    PMID: 12503884
    Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.
    Matched MeSH terms: Elapidae*
  17. Yap MK, Tan NH, Sim SM, Fung SY
    Toxicon, 2013 Jun;68:18-23.
    PMID: 23537711 DOI: 10.1016/j.toxicon.2013.02.017
    Existing protocols for antivenom treatment of snake envenomations are generally not well optimized due partly to inadequate knowledge of the toxicokinetics of venoms. The toxicokinetics of Naja sputatrix (Javan spitting cobra) venom was investigated following intravenous and intramuscular injections of the venom into rabbits using double-sandwich ELISA. The toxicokinetics of the venom injected intravenously fitted a two-compartment model. When the venom was injected intramuscularly, the serum concentration-time profile exhibited a more complex absorption and/or distribution pattern. Nevertheless, the terminal half-life, volume of distribution by area and systemic clearance of the venom injected intramuscularly were not significantly different (p > 0.05) from that of the venom injected intravenously. The systemic bioavailability of the venom antigens injected by intramuscular route was 41.7%. Our toxicokinetic finding is consistent with other reports, and may indicate that some cobra venom toxins have high affinity for the tissues at the site of injection. Our results suggest that the intramuscular route of administration doesn't significantly alter the toxicokinetics of N. sputatrix venom although it significantly reduces the systemic bioavailability of the venom.
    Matched MeSH terms: Elapidae*
  18. Nadchatram M
    Trop Biomed, 2006 Jun;23(1):1-22.
    PMID: 17041547 MyJurnal
    Some 2,000 species of mites of the family Trombiculidae are known in the world. The 6-legged larvae are mostly ectoparasites of reptiles, birds, mammals and invertebrates. Their 8-legged active nymphs and adults are free-living predators. In the Asia-Pacific region, a few species in various genera are vectors of scrub typhus and scrub-itch. In this a paper, a very bizarre trombiculid species, Vatacarus ipoides Southcott 1957, endoparasitic in the trachea of the amphibious sea snake, Laticauda colubrina (Schenider) is re-described based mostly on new-born larvae reared in the laboratory. Life history study of the mite produced very novel and interesting results. A brief account of the life-cycle was presented at the first laboratory demonstration of the Malaysian Society of Parasitology and Tropical Medicine Meeting by Nadchatram and Audy (1965). The life history is illustrated and described here in greater detail. The active nymphal, and the akinetic teleiophane stages are bypassed, which is unusual in the life-cycle of the family Trombiculidae. Also, the larva is the only stage in the life-cycle that feeds. The sexes are predetermined in the larval neosomatic stage and give rise to small males and bigger females. Having obtained adults of the species, by rearing, it is deemed unnecessary for the original proposal by Southcott to erect a new family, Vatacaridae, because the adults share all the attributes of the family Trombiculidae. The male and female obtained through laboratory rearing are illustrated for the first time. Relationship of V. ipoides with Laticauda snakes show close host-specificity, in a group of acarines that are generally habitat-specific. Possible explanations for their association are discussed. The unusual morphology and the formation of new structures during an instar is of ontogenetic and evolutionary importance. The hypertrophic larvae are superficially vermiform, rather than typically acarine in shape. This, and other biological features, necessitated the proposal of new morphological terms, and they are discussed here.
    Matched MeSH terms: Elapidae/parasitology*
  19. Ratanabanangkoon K, Tan KY, Pruksaphon K, Klinpayom C, Gutiérrez JM, Quraishi NH, et al.
    Sci Rep, 2020 07 09;10(1):11261.
    PMID: 32647261 DOI: 10.1038/s41598-020-66657-8
    Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. Snake antivenoms are mostly effective against the venoms used in their production. It is thus crucial that effective and affordable antivenom(s) with wide para-specificity, capable of neutralizing the venoms of a large number of snakes, be produced. Here we studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a 'diverse toxin repertoire' consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species. This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. We now show that the antiserum can neutralize 9 out of 10 additional neurotoxic venoms. Altogether, 36 snake venoms belonging to 10 genera from 4 continents were neutralized by the antiserum. Toxin profiles previously generated using proteomic techniques of these 36 venoms identified α-neurotoxins, β-neurotoxins, and cytotoxins as predominant toxins presumably neutralized by the antiserum. The bases for the wide para-specificity of the antiserum are discussed. These findings indicate that it is feasible to generate antivenoms of wide para-specificity against elapid neurotoxic venoms from different regions in the world and raises the possibility of a universal neurotoxic antivenom. This should reduce the mortality resulting from neurotoxic snakebite envenomation.
    Matched MeSH terms: Elapidae
  20. Lee ML, Fung SY, Chung I, Pailoor J, Cheah SH, Tan NH
    Int J Med Sci, 2014;11(6):593-601.
    PMID: 24782648 DOI: 10.7150/ijms.8096
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.
    Matched MeSH terms: Elapidae*
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