{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:35Z","timestamp":1787030135238,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship","award":["1154503"],"award-info":[{"award-number":["1154503"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship","award":["1110343"],"award-info":[{"award-number":["1110343"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship","award":["202102010282"],"award-info":[{"award-number":["202102010282"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship","award":["2022A1515012095"],"award-info":[{"award-number":["2022A1515012095"]}]},{"name":"NHMRC Centres for Research Excellence","award":["1154503"],"award-info":[{"award-number":["1154503"]}]},{"name":"NHMRC Centres for Research Excellence","award":["1110343"],"award-info":[{"award-number":["1110343"]}]},{"name":"NHMRC Centres for Research Excellence","award":["202102010282"],"award-info":[{"award-number":["202102010282"]}]},{"name":"NHMRC Centres for Research Excellence","award":["2022A1515012095"],"award-info":[{"award-number":["2022A1515012095"]}]},{"name":"2021 Guangzhou Science and Technology Program City and University (Hospital)","award":["1154503"],"award-info":[{"award-number":["1154503"]}]},{"name":"2021 Guangzhou Science and Technology Program City and University (Hospital)","award":["1110343"],"award-info":[{"award-number":["1110343"]}]},{"name":"2021 Guangzhou Science and Technology Program City and University (Hospital)","award":["202102010282"],"award-info":[{"award-number":["202102010282"]}]},{"name":"2021 Guangzhou Science and Technology Program City and University (Hospital)","award":["2022A1515012095"],"award-info":[{"award-number":["2022A1515012095"]}]},{"name":"2022 General project Grant of Natural Science Foundation of Guangdong provincial basic and applied basic research foundation","award":["1154503"],"award-info":[{"award-number":["1154503"]}]},{"name":"2022 General project Grant of Natural Science Foundation of Guangdong provincial basic and applied basic research foundation","award":["1110343"],"award-info":[{"award-number":["1110343"]}]},{"name":"2022 General project Grant of Natural Science Foundation of Guangdong provincial basic and applied basic research foundation","award":["202102010282"],"award-info":[{"award-number":["202102010282"]}]},{"name":"2022 General project Grant of Natural Science Foundation of Guangdong provincial basic and applied basic research foundation","award":["2022A1515012095"],"award-info":[{"award-number":["2022A1515012095"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Daboia siamensis (Russell\u2019s viper) is a highly venomous and medically important snake in China, as well as much of Asia. There is minimal information on the pharmacological activity of the venom of the Chinese species, and currently no commercially available specific antivenom in China. This has led to the use of non-specific antivenoms to treat D. siamensis envenomation. In this study, the in vitro neurotoxicity and myotoxicity of D. siamensis venom was examined and the efficacy of four antivenoms was investigated, including the recently developed Chinese D. siamensis monovalent antivenom (C-DsMAV) and three commercially available antivenoms (Thai D. siamensis (Thai-DsMAV) monovalent antivenom, Deinagkistrodon acutus monovalent antivenom (DaAV), and Gloydius brevicaudus monovalent antivenom (GbAV). D. siamensis venom (10\u201330 \u00b5g\/mL) caused the concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve muscle preparation, without abolishing contractile responses to exogenous agonists ACh or CCh, indicating pre-synaptic neurotoxicity. Myotoxicity was also evident at these concentrations with inhibition of direct twitches, an increase in baseline tension, and the partial inhibition of ACh, CCh, and KCl responses. The prior addition of C-DsMAV or Thai-DsMAV prevented the neurotoxic and myotoxic activity of D. siamensis venom (10 \u00b5g\/mL). The addition of non-specific antivenoms (GbAV and DaAV) partially prevented the neurotoxic activity of venom (10 \u00b5g\/mL) but failed to neutralize the myotoxic effects. We have shown that D. siamensis venom exhibits in vitro weak presynaptic neurotoxicity and myotoxicity, which can be prevented by the pre-addition of the Chinese and Thai Russell\u2019s viper antivenoms. Non-specific antivenoms were poorly efficacious. There should be further development of a monospecific antivenom against D. siamensis envenomation in China.<\/jats:p>","DOI":"10.3390\/toxins14070505","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T22:38:50Z","timestamp":1658443130000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In Vitro Toxicity of Chinese Russell\u2019s Viper (Daboia siamensis) Venom and Neutralisation by Antivenoms"],"prefix":"10.3390","volume":"14","author":[{"given":"Mimi","family":"Lay","sequence":"first","affiliation":[{"name":"Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liang","sequence":"additional","affiliation":[{"name":"Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"},{"name":"Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Rd., Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1519-7419","authenticated-orcid":false,"given":"Geoffrey K.","family":"Isbister","sequence":"additional","affiliation":[{"name":"Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"},{"name":"Clinical Toxicology Research Group, University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9919-0144","authenticated-orcid":false,"given":"Wayne C.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"ref_1","first-page":"33","article-title":"The genus Daboia (Serpentes: Viperidae): Russell\u2019s Viper","volume":"23","year":"1998","journal-title":"Hamadryad"},{"key":"ref_2","first-page":"219","article-title":"Russell\u2019s viper in Indonesia: Snakebite and systematics","volume":"70","author":"Belt","year":"1997","journal-title":"Symp. Zool. Soc. Lond."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Brent, J., Burkhart, K., Dargan, P., Hatten, B., Megarbane, B., and Palmer, R. (2016). Asian Snakes. Critical Care Toxicology, Springer.","DOI":"10.1007\/978-3-319-20790-2"},{"key":"ref_4","first-page":"209","article-title":"Phylogeography of the Russell\u2019s viper (Daboia russelii) complex in relation to variation in the colour pattern and symptoms of envenoming","volume":"17","author":"Thorpe","year":"2007","journal-title":"Herpetol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1016\/j.ekir.2019.05.017","article-title":"Acute Kidney Injury Following Eastern Russell\u2019s Viper (Daboia siamensis) Snakebite in Myanmar","volume":"4","author":"Alfred","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S0041-0101(02)00137-X","article-title":"Russell\u2019s viper snakebite in Taiwan: Differences from other Asian countries","volume":"40","author":"Hung","year":"2002","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1432-1033.1992.tb17330.x","article-title":"Characterisation and molecular cloning of neurotoxic phospholipases A2 from Taiwan viper (Vipera russelli formosensis)","volume":"209","author":"Wang","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/0035-9203(89)90311-8","article-title":"Snake venoms in science and clinical medicine 1. Russell\u2019s viper: Biology, venom and treatment of bites","volume":"83","author":"Warrell","year":"1989","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Silva, A., Johnston, C., Kuruppu, S., Kneisz, D., Maduwage, K., Kleifeld, O., Smith, A.I., Siribaddana, S., Buckley, N.A., and Hodgson, W.C. (2016). Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell\u2019s Viper (Daboia russelii) Envenoming. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005172"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12640-016-9650-4","article-title":"Neurotoxicity in Sri Lankan Russell\u2019s Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin","volume":"31","author":"Silva","year":"2017","journal-title":"Neurotox Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3109\/15563650.2016.1143556","article-title":"Neurotoxicity in Russell\u2019s viper (Daboia russelii) envenoming in Sri Lanka: A clinical and neurophysiological study","volume":"54","author":"Silva","year":"2016","journal-title":"Clin. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1107\/S0907444907016204","article-title":"Structural and pharmacological comparison of daboiatoxin from Daboia russelli siamensis with viperotoxin F and vipoxin from other vipers","volume":"63","author":"Gopalan","year":"2007","journal-title":"Acta Crystallogr. Sect. D."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e20190048","DOI":"10.1590\/1678-9199-jvatitd-2019-0048","article-title":"Proteomics and antivenom immunoprofiling of Russell\u2019s viper (Daboia siamensis) venom from Thailand and Indonesia","volume":"26","author":"Lingam","year":"2020","journal-title":"J. Venom. Anim. Toxins Incl. Trop Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0041-0101(94)00133-S","article-title":"A Major Lethal factor of the Venom of Burmese Russell\u2019s Viper (Daboia russelli siamensis): Isolation, N-Terminal sequencing and biological activities of daboiatoxin","volume":"33","author":"Thwin","year":"1995","journal-title":"Toxicon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jprot.2009.01.006","article-title":"Snake venomics of the Siamese Russell\u2019s viper (Daboia russelli siamensis)\u2014Relation to pharmacological activities","volume":"72","author":"Risch","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8545","DOI":"10.1038\/s41598-018-25955-y","article-title":"Venom proteomics and antivenom neutralization for the Chinese Eastern Russell\u2019s viper, Daboia siamensis from Guangxi and Taiwan","volume":"8","author":"Tan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0041-0101(95)00114-X","article-title":"Two types of Russell\u2019s viper revealed by variation in Phospholipases A2 from venom of the subspecies","volume":"34","author":"Tsai","year":"1996","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108634","DOI":"10.1016\/j.cbpc.2019.108634","article-title":"Complementary DNA library of Myanmar Russell\u2019s viper (Daboia russelii siamensis) venom gland","volume":"227","author":"Yee","year":"2020","journal-title":"Comp. Biochem. Physiol. C Toxicol Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sanz, L., Quesada-bernat, S., Chen, P.Y., Lee, C.D., Chiang, J.R., and Calvete, J.J. (2018). Translational Venomics: Third-Generation Antivenomics of Anti-Siamese Russell\u2019s Viper, Daboia siamensis, Antivenom Manufactured in Taiwan CDC\u2019s Vaccine Center. Trop. Med. Infect. Dis., 3.","DOI":"10.3390\/tropicalmed3020066"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jprot.2015.08.017","article-title":"Functional venomics of the Sri Lankan Russell\u2019s viper (Daboia russelii) and its toxinological correlations","volume":"128","author":"Tan","year":"2015","journal-title":"J. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Alsolaiss, J., Charoenpitakchai, M., Wiwatwarayos, K., Sookprasert, N., Harrison, R.A., Chaiyabutr, N., Chanhome, L., Tan, C.H., and Casewell, N.R. (2019). Evaluation of the geographical utility of Eastern Russell\u2019s viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity. PLoS Negl. Trop. Dis., 13.","DOI":"10.1101\/591305"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.actatropica.2013.12.015","article-title":"Cross neutralization of common Southeast Asian viperid venoms by a Thai polyvalent snake antivenom (Hemato Polyvalent Snake Antivenom)","volume":"132","author":"Leong","year":"2014","journal-title":"Acta Trop."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.toxicon.2011.05.007","article-title":"Effect of purified viper venom-factor X activator (RVV-X) on renal hemodynamics, renal functions, and coagulopathy in rats","volume":"58","author":"Suntravat","year":"2011","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chaisukal, J., Khow, O., Wiwatwarayos, K., Rusmili, M.R.A., Prasert, W., Othman, I., Zainal Abidin, S.A., Charoenpitakchai, M., Hodgson, W.C., and Chanhome, L. (2021). A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell\u2019s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury. Toxins, 13.","DOI":"10.3390\/toxins13080521"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.trstmh.2005.07.020","article-title":"Antivenom treatment and renal dysfunction in Russell\u2019s viper snakebite in Taiwan: A case series","volume":"100","author":"Hung","year":"2006","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/14789450.2018.1528150","article-title":"Proteomic analysis reveals geographic variation in venom compostion of Russell\u2019s viper in the Indian subcontinent: Implications for clinical manifestations post-envenoming and antivenom treatment","volume":"15","author":"Kalita","year":"2018","journal-title":"Expert Rev. Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105311","DOI":"10.1016\/j.actatropica.2019.105311","article-title":"Geographical variations in king cobra (Ophiophagus hannah) venom from Thailand, Malaysia, Indonesia and China: On venom lethality, antivenom immunoreactivity and in vivo neutralization","volume":"203","author":"Tan","year":"2020","journal-title":"Acta Trop."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Silva, A., Hodgson, W.C., and Isbister, G.K. (2016). Cross-Neutralisation of In Vitro neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms. Toxins, 8.","DOI":"10.3390\/toxins8100302"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.toxicon.2017.10.014","article-title":"Cross reactivity and lethality neutralization of venoms of Indonesia Trimeresurus complex species by Thai Green Pit Viper Antivenom","volume":"140","author":"Tan","year":"2017","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.toxlet.2012.02.001","article-title":"Solving the \u2018Brown snake paradox\u2019: In vitro characterisation of Australasian snake presynaptic neurotoxin activity","volume":"210","author":"Barber","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liang, Q., Huynh, T.M., Ng, Y.N., Isbister, G.K., and Hodgson, W.C. (2021). In Vitro Neurotoxicity of Chinese Krait (Bungarus multicinctus) Venom and Neutralization by Antivenoms. Toxins, 13.","DOI":"10.3390\/toxins13010049"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0041-0101(00)00117-3","article-title":"A pharmacological examination of venoms from three species of death adder (Acanthophis antarcticus, Acanthophis praelongus and Acanthophis pyrrhus)","volume":"39","author":"Wickramaratna","year":"2001","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1007\/s00018-018-2893-x","article-title":"Defining the role of post-synaptic \u03b1-neurotoxins in paralysis due to snake envenoming in humans","volume":"75","author":"Silva","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0041-0101(94)90078-7","article-title":"Screening of snake venoms for neurotoxic and myotoxic effects using simple In-vitro preparations from rodents and chicks","volume":"32","author":"Harvey","year":"1994","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Senji Laxme, R.R., Khochare, S., Attarde, S., Suranse, V., Iyer, A., Casewell, N.R., Whitaker, R., Martin, G., and Sunagar, K. (2021). Biogeographic venom variation in Russell\u2019s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009247"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.toxicon.2004.08.005","article-title":"The efficacy of two antivenoms against the in vitro myotoxic effects of black snake (Pseudechis) venoms in the chick biventer cervicis nerve-muscle preparation","volume":"44","author":"Ramasamy","year":"2004","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/ki.1997.267","article-title":"Renal lesions in rhabdomyolysis caused by Pseudachis australis snake myotoxin","volume":"51","author":"Ponraj","year":"1997","journal-title":"Kidney Int."},{"key":"ref_38","unstructured":"(2018). Experts Group of Snake-bites Rescue and Treatment Consensus in China Expert Consensus on China Snake-bites rescue and Treatment. Chin. J. Emer. Med., 27, 1315\u20131322."},{"key":"ref_39","unstructured":"Liang, Q. (2021). Chinese Daboia siamensis Clinical Care and Symptoms, The First Affiliated Hospital of Guangzhou Medical University."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jprot.2014.01.019","article-title":"Proteomic and biochemical analysis of short-tailed pit viper (Gloydius brevicaudus) venom: Age-related variation and composition-activity correlation","volume":"105","author":"Gao","year":"2014","journal-title":"J. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/0041-0101(96)00067-0","article-title":"Molecular cloning and deduced primary structures of acidic and basic phospholipases A2 from the venom of Deinagkistrodon acutus","volume":"34","author":"Wang","year":"1996","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tasoulis, T., and Isbister, G.K. (2017). A review and Database of Snake Venom Proteomes. Toxins, 9.","DOI":"10.3390\/toxins9090290"},{"key":"ref_43","first-page":"17","article-title":"The in vitro toxicity of venoms from South Asian Hump-nosed pit vipers (Viperidae; Hypnale)","volume":"2","author":"Maduwage","year":"2011","journal-title":"J. Venom. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chaisukal, J., Rusmili, M.R.A., Alsolaiss, J., Albulescu, L., Harrison, R.A., Othman, I., and Casewell, N.R. (2020). In Vitro Immunological Cross-Reactivity of Thai Polyvalent and Monovalent Antivenoms with Asian Viper Venoms. Toxins, 12.","DOI":"10.3390\/toxins12120766"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/7\/505\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:53Z","timestamp":1760140493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/7\/505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,20]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["toxins14070505"],"URL":"https:\/\/doi.org\/10.3390\/toxins14070505","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,20]]}}}