{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T19:46:24Z","timestamp":1783107984509,"version":"3.54.6"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Skin blistering as a result of snakebite envenomation is characteristic of some bites, however little is known regarding the mechanism of blister formation or the composition of the blister fluid. In order to investigate if blister fluid proteomes from humans suffering snakebite envenomation could provide insights on the pathophysiology of these skin alterations, blister fluid was collected from six patients upon presentation at a clinic in India bitten by three species of snakes, Daboia russelii (3), Hypnale hypnale (2), or Naja naja (1). Standard clinical data were recorded throughout the treatment. Approximately 805 proteins were identified in blister fluids using proteomic analyses. Informatics analyses of the proteomes identified the top biological response categories as: platelet degranulation, innate immune response, receptor-mediated endocytosis, complement activation, and blood coagulation. Hierarchical clustering did not show a clear segregation of patients\u2019 proteomes being associated with the species of snake involved, suggesting that either the proteomic profiles described reflect a general response to venom-induced tissue damage or more patient data sets will be required to observe significant differences. Finally, it is of interest that venom proteins were also identified in the blister fluids suggesting that this fluid may serve as a reservoir of venom biologically active proteins\/toxins, and as such, may indicate the clinical value of removing blister fluid to attenuate further tissue damage.<\/jats:p>","DOI":"10.3390\/toxins11050246","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T08:51:44Z","timestamp":1556614304000},"page":"246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Proteomic Analysis of Human Blister Fluids Following Envenomation by Three Snake Species in India: Differential Markers for Venom Mechanisms of Action"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-7071","authenticated-orcid":false,"given":"J\u00e9ssica K. A.","family":"Mac\u00eado","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Cancer Biology, University of Virginia, School of Medicine, Charlottesville, VA 22908-734, USA"},{"name":"Department of Cell Biology, Brazilian Center of Protein Research, University of Brasilia, Brasilia\/DF 70297-400, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph K.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Little Flower Hospital, Angamaly 683572, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Menon","sequence":"additional","affiliation":[{"name":"Sree Naryana Institute of Medical Science, Kerala 683594, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Escalante","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, School of Microbiology, University of Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rucavado","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, School of Microbiology, University of Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3081","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto Clodomiro Picado, School of Microbiology, University of Costa Rica, San Jos\u00e9 11501-2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay W.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cancer Biology, University of Virginia, School of Medicine, Charlottesville, VA 22908-734, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0001018","article-title":"Snakebite mortality in India: A nationally representative mortality survey","volume":"5","author":"Mohapatra","year":"2011","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_3","first-page":"38","article-title":"New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India","volume":"138","author":"Warrell","year":"2013","journal-title":"Indian J. Med. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1580\/06-WEME-CO-023R1.1","article-title":"Snakes of medical importance in India: Is the concept of the \u201cBig 4\u201d still relevant and useful?","volume":"18","author":"Simpson","year":"2007","journal-title":"Wilderness Environ. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1021\/pr900489m","article-title":"Wound exudate as a proteomic window to reveal different mechanisms of tissue damage by snake venom toxins","volume":"8","author":"Escalante","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1002\/pmic.200600938","article-title":"Suction blister fluid as potential body fluid for biomarker proteins","volume":"7","author":"Kool","year":"2007","journal-title":"Proteomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1021\/pr100456d","article-title":"Differential Proteomic Analysis Distinguishes Tissue Repair Biomarker Signatures in Wound Exudates Obtained from Normal Healing and Chronic Wounds","volume":"9","author":"Eming","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1080\/14789450.2018.1538800","article-title":"Metalloproteinases in disease: Identification of biomarkers of tissue damage through proteomics","volume":"15","author":"Herrera","year":"2018","journal-title":"Expert Rev. Proteomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e20180160","DOI":"10.1590\/0037-8682-0160-2018","article-title":"Venom concentrations in blisters and hemorrhagic bullae in a patient bitten by a Taiwan habu (Protobothrops mucrosquamatus)","volume":"52","author":"Lin","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1021\/pr101208f","article-title":"Proteomics of Wound Exudate in Snake Venom-Induced Pathology: Search for Biomarkers To Assess Tissue Damage and Therapeutic Success","volume":"10","author":"Rucavado","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_11","first-page":"245","article-title":"Blister formation and skin damage induced by BaP1, a haemorrhagic metalloproteinase from the venom of the snake Bothrops asper","volume":"79","author":"Rucavado","year":"1998","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Herrera, C., Mac\u00eado, J.K.A., Feoli, A., Escalante, T., Rucavado, A., Guti\u00e9rrez, J.M., and Fox, J.W. (2016). Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004599"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0003731","article-title":"Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage","volume":"9","author":"Herrera","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1038\/jid.2008.118","article-title":"Skin Pathology Induced by Snake Venom Metalloproteinase: Acute Damage, Revascularization, and Re-epithelization in a Mouse Ear Model","volume":"128","author":"Escalante","year":"2008","journal-title":"J. Invest. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/pr200847q","article-title":"Efficacy of IgG and F(ab\u2032) 2 antivenoms to neutralize snake venom-induced local tissue damage as assessed by the proteomic analysis of wound exudate","volume":"11","author":"Rucavado","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Escalante, T., Ortiz, N., Rucavado, A., Sanchez, E.F., Richardson, M., Fox, J.W., and Guti\u00e9rrez, J.M. (2011). Role of collagens and perlecan in microvascular stability: Exploring the mechanism of capillary vessel damage by snake venom metalloproteinases. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028017"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"W566","DOI":"10.1093\/nar\/gkv468","article-title":"ClustVis: A web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap","volume":"43","author":"Metsalu","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/5\/246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:48:09Z","timestamp":1760186889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/5\/246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,30]]},"references-count":19,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["toxins11050246"],"URL":"https:\/\/doi.org\/10.3390\/toxins11050246","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,30]]}}}