{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:15:17Z","timestamp":1784304917325,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Office of Research Development, Phramongkutklao College of Medicine and Phramongkutklao Hospital","award":["1110343"],"award-info":[{"award-number":["1110343"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence","award":["1110343"],"award-info":[{"award-number":["1110343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported in a patient who had a long length of hospital stay. In this study, we determined the effect of C. rhodostoma envenoming on cardiovascular disturbances and the associated morphological changes in the liver, heart and kidneys using animal models. We also evaluated the efficacy of Hemato polyvalent antivenom (HPAV; Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society, Thailand) in neutralising the histopathological effects of C. rhodostoma venom. The intravenous (i.v.) administration of C. rhodostoma venom (1000 \u00b5g\/kg) caused a rapid decrease in mean arterial pressure (MAP) followed by complete cardiac collapse in anaesthetized rats. Moreover, the intraperitoneal (i.p.) administration of C. rhodostoma venom (11.1 mg\/kg; 3 \u00d7 LD50) for 24 h caused cellular lesions in the liver and heart tissues. C. rhodostoma venom also induced nephrotoxicity, as indicated by the presence of tubular injury, interstitial vascular congestion and inflammatory infiltration in the whole area of the kidney. The administration of HPAV, at manufacturer-recommended doses, 15 min prior to or after the addition of C. rhodostoma venom reduced the extent of the morphological changes in the liver, heart and kidneys. This study found that experimental C. rhodostoma envenoming induced cardiovascular disturbances, hepatotoxicity and nephrotoxicity. We also highlighted the potential broad utility of HPAV to neutralise the histopathological effects of C. rhodostoma venom. The early delivery of antivenom appears capable of preventing envenoming outcomes.<\/jats:p>","DOI":"10.3390\/toxins14090601","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T02:09:36Z","timestamp":1661911776000},"page":"601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Histopathological Changes in the Liver, Heart and Kidneys Following Malayan Pit Viper (Calloselasma rhodostoma) Envenoming and the Neutralising Effects of Hemato Polyvalent Snake Antivenom"],"prefix":"10.3390","volume":"14","author":[{"given":"Wipapan","family":"Khimmaktong","sequence":"first","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazmi","family":"Nuanyaem","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":"Nissara","family":"Lorthong","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"}]},{"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, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janeyuth","family":"Chaisakul","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Phramongkutklao College of Medicine, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0140-6736(18)31224-8","article-title":"Vulnerability to snakebite envenoming: A global mapping of hotspots","volume":"392","author":"Longbottom","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17079","DOI":"10.1038\/nrdp.2017.79","article-title":"Snakebite envenoming","volume":"3","author":"Gutierrez","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","unstructured":"WHO (2016). Venomous snakes of the South-East Asia Region, their venoms and pathophysiology of human envenoming. Guidelines for the Management of Snake-Bites, WHO, Regional Office for South-East Asia. [2nd ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gopalakrishnakone, P. (2015). Snakebite and Envenomation Management in Malaysia. Clinical Toxinology in Asia Pacific and Africa, Toxinology, Springer Science.","DOI":"10.1007\/978-94-007-6386-9"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jprot.2016.07.006","article-title":"Venomics of Calloselasma rhodostoma, the Malayan pit viper: A complex toxin arsenal unraveled","volume":"148","author":"Tang","year":"2016","journal-title":"J. Proteom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxicon.2019.08.004","article-title":"Comparative proteomes, immunoreactivities and neutralization of procoagulant activities of Calloselasma rhodostoma (Malayan pit viper) venoms from four regions in Southeast Asia","volume":"169","author":"Tang","year":"2019","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3390\/toxins5040665","article-title":"The snake venom rhodocytin from Calloselasma rhodostoma- a clinically important toxin and a useful experimental tool for studies of C-type lectin-like receptor 2 (CLEC-2)","volume":"5","author":"Bruserud","year":"2013","journal-title":"Toxins"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kunalan, S., Othman, I., Syed Hassan, S., and Hodgson, W.C. (2018). Proteomic Characterization of Two Medically Important Malaysian Snake Venoms, Calloselasma rhodostoma (Malayan Pit Viper) and Ophiophagus hannah (King Cobra). Toxins, 10.","DOI":"10.3390\/toxins10110434"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"342","DOI":"10.7205\/MILMED.170.4.342","article-title":"A study of 225 Malayan pit viper bites in Thailand","volume":"170","author":"Wongtongkam","year":"2005","journal-title":"Mil. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.toxicon.2007.08.007","article-title":"Systemic and local myotoxicity induced by snake venom group II phospholipases A2: Comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue","volume":"51","author":"Gutierrez","year":"2008","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.toxicon.2003.11.005","article-title":"Skeletal muscle degeneration induced by venom phospholipases A2: Insights into the mechanisms of local and systemic myotoxicity","volume":"42","author":"Gutierrez","year":"2003","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.toxicon.2009.01.038","article-title":"Experimental pathology of local tissue damage induced by Bothrops asper snake venom","volume":"54","author":"Gutierrez","year":"2009","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1440-1797.2006.00599.x","article-title":"Snakebite nephropathy","volume":"11","author":"Sitprija","year":"2006","journal-title":"Nephrology (Carlton)"},{"key":"ref_14","first-page":"433","article-title":"Moving towards the elimination of rabies in Thailand","volume":"91","author":"Kasempimolporn","year":"2008","journal-title":"J. Med Assoc. Thail. = Chotmaihet Thangphaet"},{"key":"ref_15","first-page":"93","article-title":"Duration after Malayan Pit Viper Bite to Detect Coagulopathy in Songklanagarind Hospital","volume":"38","author":"Kraisawat","year":"2020","journal-title":"J. Health Sci. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.2147\/TCRM.S337199","article-title":"Malayan Pit Viper Envenomation and Treatment in Thailand","volume":"17","author":"Tangtrongchitr","year":"2021","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Rusmili, M.R.A., Alsolaiss, J., Albulescu, L.O., 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"},{"key":"ref_18","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_19","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_20","unstructured":"WHO (2019, February 26). Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins. Geneva. Available online: https:\/\/www.who.int\/biologicals\/expert_committee\/Antivenom_WHO_Guidelines_DJW_DEB_mn_cp.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.toxicon.2012.09.004","article-title":"Snake venom metalloproteinases","volume":"62","author":"Markland","year":"2013","journal-title":"Toxicon"},{"key":"ref_22","first-page":"423","article-title":"Venomous and poisonous animals. II. Viper bites","volume":"66","author":"Chippaux","year":"2006","journal-title":"Med. Trop. Rev. Du Corps De Sante Colonial"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"626","DOI":"10.2174\/0929866525666180614112935","article-title":"Snake Venom as an Effective Tool against Colorectal Cancer","volume":"25","author":"Uzair","year":"2018","journal-title":"Protein Pept. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.toxicon.2003.11.002","article-title":"Excitement ahead: Structure, function and mechanism of snake venom phospholipase A2 enzymes","volume":"42","author":"Kini","year":"2003","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Rusmili, M.R., 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_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.toxlet.2012.06.015","article-title":"In vivo and in vitro cardiovascular effects of Papuan taipan (Oxyuranus scutellatus) venom: Exploring \u201csudden collapse\u201d","volume":"213","author":"Chaisakul","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejphar.2013.11.028","article-title":"Hypotensive and vascular relaxant effects of phospholipase A2 toxins from Papuan taipan (Oxyuranus scutellatus) venom","volume":"723","author":"Chaisakul","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.toxicon.2015.05.001","article-title":"Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis","volume":"102","author":"Chaisakul","year":"2015","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1678-9199-20-42","article-title":"Hepatotoxicity and oxidative stress induced by Naja haje crude venom","volume":"20","author":"Dkhil","year":"2014","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_30","first-page":"63","article-title":"Liver dysfunction in patients bitten by Crotalus durissus terrificus (Laurenti, 1768) snakes in Botucatu (State of Sao Paulo, Brazil)","volume":"37","author":"Barraviera","year":"1995","journal-title":"Rev. Do Inst. De Med. Trop. De Sao Paulo"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.bbagen.2011.04.003","article-title":"Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom","volume":"1810","author":"Naumann","year":"2011","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.semnephrol.2008.04.005","article-title":"Snakebite nephrotoxicity in Asia","volume":"28","author":"Kanjanabuch","year":"2008","journal-title":"Semin. Nephrol."},{"key":"ref_33","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_34","unstructured":"Finney, D. (1971). Probit Analysis, Cambridge University. [3rd ed.]."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"e000921","DOI":"10.1161\/JAHA.114.000921","article-title":"Functional and histological assessment of an experimental model of Takotsubo\u2019s cardiomyopathy","volume":"3","author":"Sachdeva","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4038\/cjsbs.v38i1.1321","article-title":"Histopathological Changes in Brain, Kidney and Liver of Mice following Intramuscular Administration of Krait Venom","volume":"38","author":"Nanayakkara","year":"2009","journal-title":"Cey. J. Sci. (Bio. Sci.)"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/9\/601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:20:37Z","timestamp":1760142037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/9\/601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["toxins14090601"],"URL":"https:\/\/doi.org\/10.3390\/toxins14090601","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,30]]}}}