{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:58:58Z","timestamp":1791575938695,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,29]],"date-time":"2024-12-29T00:00:00Z","timestamp":1735430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ananda Mahidol Foundation","award":["2023\u20132026"],"award-info":[{"award-number":["2023\u20132026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>An understanding of snake venom pharmacokinetics is essential for determining clinical outcomes of envenoming and developing therapeutic approaches to the treatment of envenoming, especially regarding the timing and optimal dosage of antivenom administration. Daboia siamensis (Eastern Russell\u2019s viper) envenoming causes systemic coagulopathy and severe hemorrhage including acute kidney injury. These toxic outcomes can be diminished by the administration of high quantities of Russell\u2019s viper antivenom. This study aimed to determine the correlation between the clinical profiles of D. siamensis envenomed patients and experimental data by measuring plasma venom concentration and conducting histopathological analyses of heart, kidney, and liver tissues in rats 6 h after experimental D. siamensis envenomation. Intramuscular (i.m.) administration of D. siamensis venom to anesthetized rats (200 \u00b5g\/kg) resulted in a rapid absorption of venom which reached a peak concentration at 60 min before declining and then plateauing. Urine samples detected 209.3 \u00b1 21.6 ng\/mL of D. siamensis venom following i.m. administration at 6 h. Histopathological studies showed morphological changes in heart, kidney, and liver tissues following 3 h experimental envenoming and exhibited a higher degree of severity at 6 h. A retrospective study of the clinical profile and laboratory examination of Russell\u2019s viper envenomed patients in Central Thailand was also evaluated, showing that systemic coagulopathy and local effects were commonly observed in the early stage of D. siamensis envenoming. An abnormal increase in creatinine levels was found in 13.6% of the population. Early administration of specific antivenom within 1\u20132 h following envenoming is highly recommended to prevent life-threatening outcomes such as severe coagulation and acute kidney injury.<\/jats:p>","DOI":"10.3390\/toxins17010010","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T04:10:23Z","timestamp":1735618223000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Snake Venom Pharmacokinetics and Acute Toxic Outcomes Following Daboia siamensis Envenoming: Experimental and Clinical Correlations"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9349-2088","authenticated-orcid":false,"given":"Sethapong","family":"Lertsakulbunlue","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wipapan","family":"Khimmaktong","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orawan","family":"Khow","sequence":"additional","affiliation":[{"name":"Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wittawat","family":"Chantkran","sequence":"additional","affiliation":[{"name":"Department of Pathology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jureeporn","family":"Noiphrom","sequence":"additional","affiliation":[{"name":"Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanyanat","family":"Promruangreang","sequence":"additional","affiliation":[{"name":"Forensic Toxicology Unit, Department of Forensic Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-5000","authenticated-orcid":false,"given":"Lawan","family":"Chanhome","sequence":"additional","affiliation":[{"name":"Snake Farm, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-8792","authenticated-orcid":false,"given":"Janeyuth","family":"Chaisakul","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kasturiratne, A., Wickremasinghe, A.R., de Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna, R., Savioli, L., Lalloo, D.G., and de Silva, H.J. (2008). The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050218"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40409-017-0127-6","article-title":"Snakebite Envenomation Turns Again into a Neglected Tropical Disease!","volume":"23","author":"Chippaux","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17079","DOI":"10.1038\/nrdp.2017.79","article-title":"Correction: Snakebite Envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","unstructured":"WHO World Health Organization (WHO) Regional Office in South-East Asia (2016). Guidelines for Management of Snakebites, WHO Regional Office in South-East Asia. [2nd ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jprot.2018.05.003","article-title":"Proteomics, Functional Characterization and Antivenom Neutralization of the Venom of Pakistani Russell\u2019s Viper (Daboia Russelii) from the Wild","volume":"183","author":"Faisal","year":"2018","journal-title":"J. Proteom."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0140-6736(85)91550-8","article-title":"Maung-Maung-Lay Bites by Russell\u2019s viper (Vipera russelli siamensis) in Burma: Haemostatic, vascular, and renal disturbances and response to treatment","volume":"326","author":"Phillips","year":"1985","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1440-1797.2006.00599.x","article-title":"Snakebite Nephropathy (Review Article)","volume":"11","author":"Sitprija","year":"2006","journal-title":"Nephrology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maduwage, K., and Isbister, G.K. (2014). Current Treatment for Venom-Induced Consumption Coagulopathy Resulting from Snakebite. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003220"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1678-9199-20-33","article-title":"Viper Bites Complicate Chronic Agrochemical Nephropathy in Rural Sri Lanka","volume":"20","author":"Silva","year":"2014","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lay, M., and Hodgson, W.C. (2024). A Comparison of the Efficacy of Antivenoms and Varespladib against the In Vitro Pre-Synaptic Neurotoxicity of Thai and Javanese Russell\u2019s Viper (Daboia Spp.) Venoms. Toxins, 16.","DOI":"10.3390\/toxins16030124"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Khow, O., Wiwatwarayos, K., Rusmili, M.R.A., Prasert, W., Othman, I., Abidin, S.A.Z., 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_13","doi-asserted-by":"crossref","unstructured":"Tan, K.Y., Tan, N.H., and Tan, C.H. (2018). Venom Proteomics and Antivenom Neutralization for the Chinese Eastern Russell\u2019s Viper, Daboia Siamensis from Guangxi and Taiwan. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-25955-y"},{"key":"ref_14","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. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.toxicon.2012.10.017","article-title":"Effects of Phospholipase A2 and Metalloprotease Fractions of Russell\u2019s Viper Venom on Cytokines and Renal Hemodynamics in Dogs","volume":"61","author":"Mitrmoonpitak","year":"2013","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.toxicon.2012.06.012","article-title":"Renal Effects and Injury Induced by Animal Toxins","volume":"60","author":"Sitprija","year":"2012","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.intimp.2013.10.007","article-title":"Pharmacokinetics of Cryptelytrops Purpureomaculatus (Mangrove Pit Viper) Venom Following Intravenous and Intramuscular Injections in Rabbits","volume":"17","author":"Sim","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3109\/15563650.2014.914526","article-title":"Pharmacokinetics and Pharmacodynamics of the Myotoxic Venom of Pseudechis Australis (Mulga Snake) in the Anesthetised Rat","volume":"52","author":"Hart","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yap, M.K.K., Tan, N.H., Sim, S.M., Fung, S.Y., and Tan, C.H. (2014). Pharmacokinetics of Naja Sumatrana (Equatorial Spitting Cobra) Venom and Its Major Toxins in Experimentally Envenomed Rabbits. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002890"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3109\/15563650.2010.533680","article-title":"Pharmacokinetic\u2013Pharmacodynamic Modeling in Overdose Patients\u2014Is It Worth the Trouble?","volume":"48","author":"Isbister","year":"2010","journal-title":"Clin. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4269\/ajtmh.1997.57.605","article-title":"Kinetic Study of Russell\u2019s Viper Venom in Envenomed Patients","volume":"57","author":"Hanvivatvong","year":"1997","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Rusmili, M.R.A., Hodgson, W.C., Hatthachote, P., Suwan, K., Inchan, A., Chanhome, L., Othman, I., and Chootip, K. (2017). A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms. Toxins, 9.","DOI":"10.3390\/toxins9040122"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40409-018-0146-y","article-title":"Non-Neurotoxic Activity of Malayan Krait (Bungarus candidus) Venom from Thailand","volume":"24","author":"Charoenpitakchai","year":"2018","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sanhajariya, S., Duffull, S., and Isbister, G. (2018). Pharmacokinetics of Snake Venom. Toxins, 10.","DOI":"10.3390\/toxins10020073"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sanhajariya, S., Isbister, G.K., and Duffull, S.B. (2020). The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom. Toxins, 12.","DOI":"10.3390\/toxins12030188"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2013.12.011","article-title":"Pharmacokinetics of the Sri Lankan Hump-Nosed Pit Viper (Hypnale hypnale) Venom Following Intravenous and Intramuscular Injections of the Venom into Rabbits","volume":"79","author":"Tan","year":"2014","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0041-0101(83)90090-9","article-title":"The Application of Immunoassay Techniques, Including Enzyme-Linked Immunosorbent Assay (ELISA), to Snake Venom Research","volume":"21","author":"Theakston","year":"1983","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0041-0101(98)00203-7","article-title":"Tests for Detection of Snake Venoms, Toxins and Venom Antibodies: Review on Recent Trends (1987\u20131997)","volume":"37","author":"Selvanayagam","year":"1999","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Choowongkomon, K., Chaisakul, J., Seetaha, S., Vasaruchapong, T., Hodgson, W.C., Rasri, N., Chaeksin, K., Boonchaleaw, S., and Sookprasert, N. (2024). Development of a Biosensor to Detect Venom of Malayan Krait (Bungarus candidus). Toxins, 16.","DOI":"10.3390\/toxins16010056"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/nm.2382","article-title":"A Pharmacological Approach to First Aid Treatment for Snakebite","volume":"17","author":"Saul","year":"2011","journal-title":"Nat. Med."},{"key":"ref_32","first-page":"1","article-title":"Effect of Antivenom on Venom Pharmacokinetics in Experimentally Envenomed Rabbits: Toward an Optimization of Antivenom Therapy","volume":"281","author":"Choumet","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100085","DOI":"10.1016\/j.toxcx.2021.100085","article-title":"Local Inflammatory Mediators Alterations Induced by Daboia siamensis Venom","volume":"12","author":"Khunsap","year":"2021","journal-title":"Toxicon X"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100046","DOI":"10.1016\/j.toxcx.2020.100046","article-title":"The Pathophysiological Effects of Russell\u2019s Viper (Daboia siamensis) Venom and Its Fractions in the Isolated Perfused Rabbit Kidney Model: A Potential Role for Platelet Activating Factor","volume":"7","author":"Chaiyabutr","year":"2020","journal-title":"Toxicon X"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.toxicon.2009.09.018","article-title":"Renal Kinetics of Bothrops alternatus (Urutu) Snake Venom in Rats","volume":"55","author":"Mello","year":"2010","journal-title":"Toxicon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1751-0813.2010.00584.x","article-title":"Prospective Determination of the Specificity of a Commercial Snake Venom Detection Kit in Urine Samples from Dogs and Cats","volume":"88","author":"Ong","year":"2010","journal-title":"Aust. Vet. J."},{"key":"ref_37","first-page":"1512","article-title":"Pharmacokinetics of Vipera aspis Venom after Experimental Envenomation in Rabbits","volume":"268","author":"Audebert","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.toxrep.2019.08.006","article-title":"Clinico-Epidemiology and Management of Russell\u2019s Viper (Daboia russelii) Envenoming in Dogs in Sri Lanka","volume":"6","author":"Adhikari","year":"2019","journal-title":"Toxicol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wedasingha, S., Isbister, G., and Silva, A. (2020). Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite. Toxins, 12.","DOI":"10.3390\/toxins12090583"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3396373","DOI":"10.1155\/2021\/3396373","article-title":"Personal Experience of Daboia Siamensis Envenomation","volume":"2021","author":"Tsai","year":"2021","journal-title":"Case Rep. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lertsakulbunlue, S., Suebtuam, R., Eamchotchawalit, T., Chantkran, W., and Chaisakul, J. (2023). Clinical Profile and Pharmacological Management of Snakebites in Community Care Units: A Retrospective Study Using Two Military Hospital Databases in South Thailand. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8070346"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4269\/ajtmh.23-0657","article-title":"Clinical Laboratory Investigations and Antivenom Administration after Malayan Pit Viper (Calloselasma rhodostoma) Envenoming: A Retrospective Study from Southernmost Thailand","volume":"110","author":"Chesor","year":"2024","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.toxicon.2010.06.026","article-title":"Hyponatraemia, Rhabdomyolysis, Alterations in Blood Pressure and Persistent Mydriasis in Patients Envenomed by Malayan Kraits (Bungarus candidus) in Southern Viet Nam","volume":"56","author":"Trinh","year":"2010","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1136\/pmj.78.919.276","article-title":"Common Krait (Bungarus caeruleus) Bite in Anuradhapura, Sri Lanka: A Prospective Clinical Study, 1996\u201398","volume":"78","author":"Kularatne","year":"2002","journal-title":"Postgrad. Med. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.toxicon.2020.09.006","article-title":"Polymorphonuclear Neutrophil Leukocytes in Snakebite Envenoming","volume":"187","author":"Zuliani","year":"2020","journal-title":"Toxicon"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ratnayake, I., Mohamed, F., Buckley, N.A., Gawarammana, I.B., Dissanayake, D.M., Chathuranga, U., Munasinghe, M., Maduwage, K., Jayamanne, S., and Endre, Z.H. (2019). Early Identification of Acute Kidney Injury in Russell\u2019s Viper (Daboia russelii) Envenoming Using Renal Biomarkers. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007486"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0041-0101(98)00214-1","article-title":"The Effects of Green Pit Viper (Trimeresurus albolabris and Trimeresurus macrops) Venom on the Fibrinolytic System in Human","volume":"37","author":"Rojnuckarin","year":"1999","journal-title":"Toxicon"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Khimmaktong, W., Nuanyaem, N., Lorthong, N., Hodgson, W.C., and Chaisakul, J. (2022). Histopathological Changes in the Liver, Heart and Kidneys Following Malayan Pit Viper (Calloselasma rhodostoma) Envenoming and the Neutralising Effects of Hemato Polyvalent Snake Antivenom. Toxins, 14.","DOI":"10.3390\/toxins14090601"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/1\/10\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:46Z","timestamp":1760115346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/1\/10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,29]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["toxins17010010"],"URL":"https:\/\/doi.org\/10.3390\/toxins17010010","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,29]]}}}