{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:14:33Z","timestamp":1785446073526,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0006427","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior \u2013 CAPES","award":["Toxinologia 23038000825\/2011-63"],"award-info":[{"award-number":["Toxinologia 23038000825\/2011-63"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Minas Gerais \u2013 FAPEMIG","award":["RCUK-CONFAP, APQ 08831-15"],"award-info":[{"award-number":["RCUK-CONFAP, APQ 08831-15"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico \u2013 CNPq","award":["PVE 71\/2013, 407266\/2013-5"],"award-info":[{"award-number":["PVE 71\/2013, 407266\/2013-5"]}]},{"name":"Wellcome Trust Pathfinder","award":["201054\/Z\/16\/Z"],"award-info":[{"award-number":["201054\/Z\/16\/Z"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico - CNPq","award":["Science Without Borders - 4803318142983356"],"award-info":[{"award-number":["Science Without Borders - 4803318142983356"]}]},{"DOI":"10.13039\/100010897","name":"Newton Fund","doi-asserted-by":"publisher","award":["MRC-CONFAP MR\/M026310\/1"],"award-info":[{"award-number":["MRC-CONFAP MR\/M026310\/1"]}],"id":[{"id":"10.13039\/100010897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0006427","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T17:33:39Z","timestamp":1523900019000},"page":"e0006427","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom"],"prefix":"10.1371","volume":"12","author":[{"given":"Stephanie","family":"Stransky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Costal-Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia","family":"Lopes-de-Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Guerra-Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9390-7207","authenticated-orcid":true,"given":"Carlos","family":"Ch\u00e1vez-Ol\u00f3rtegui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania Maria Martin","family":"Braga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"issue":"9708","key":"ref1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0140-6736(09)61159-4","article-title":"The Global Snake Bite Initiative: an antidote for snake bite","volume":"375","author":"D Williams","year":"2010","journal-title":"Lancet"},{"issue":"7618","key":"ref2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/537026a","article-title":"Vipers, mambas and taipans: the escalating health crisis over snakebites","volume":"537","author":"C Arnold","year":"2016","journal-title":"Nature"},{"key":"ref3","article-title":"Guia de Vigil\u00e2ncia Epidemiol\u00f3gica","year":"2009"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jprot.2013.05.028","article-title":"Snake venomics of Lachesis muta rhombeata and genus-wide antivenomics assessment of the paraspecific immunoreactivity of two antivenoms evidence the high compositional and immunological conservation across Lachesis","volume":"89","author":"D Pla","year":"2013","journal-title":"J Proteomics"},{"issue":"Pt B","key":"ref5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.toxicon.2015.08.029","article-title":"Identification of hyaluronidase and phospholipase B in Lachesis muta rhombeata venom","volume":"107","author":"GA Wiezel","year":"2015","journal-title":"Toxicon"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jprot.2007.10.004","article-title":"Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis","volume":"71","author":"L Sanz","year":"2008","journal-title":"J Proteomics"},{"issue":"5","key":"ref7","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0041-0101(00)00201-4","article-title":"Lachesis muta muta venom: immunological differences compared with Bothrops atrox venom and importance of specific antivenom therapy","volume":"39","author":"M Colombini","year":"2001","journal-title":"Toxicon"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jprot.2012.09.003","article-title":"Snake venomics across genus Lachesis. Ontogenetic changes in the venom composition of Lachesis stenophrys and comparative proteomics of the venoms of adult Lachesis melanocephala and Lachesis acrochorda","volume":"77","author":"M Madrigal","year":"2012","journal-title":"J Proteomics"},{"issue":"5","key":"ref9","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.toxicon.2006.11.014","article-title":"Cytotoxicity of Lachesis muta muta snake (bushmaster) venom and its purified basic phospholipase A2 (LmTX-I) in cultured cells","volume":"49","author":"DC Damico","year":"2007","journal-title":"Toxicon"},{"key":"ref10","unstructured":"Animais Pe\u00e7onhentos [Internet]. Minist\u00e9rio da Sa\u00fade. 2015 [cited 04\/02\/2015]. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dtr2004.saude.gov.br\/sinanweb\/\" xlink:type=\"simple\">http:\/\/dtr2004.saude.gov.br\/sinanweb\/<\/ext-link>."},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.toxicon.2004.12.006","article-title":"The improvement of the therapeutic anti-Lachesis muta serum production in horses","volume":"45","author":"MA Stephano","year":"2005","journal-title":"Toxicon"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0041-0101(96)00142-0","article-title":"Snakebite by the bushmaster (Lachesis muta) in Brazil: case report and review of the literature","volume":"35","author":"MT Jorge","year":"1997","journal-title":"Toxicon"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0035-9203(03)00005-1","article-title":"Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil","volume":"98","author":"PP Pardal","year":"2004","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref14","first-page":"37","article-title":"Acidente por surucucu (Lachesis muta muta) em Bel\u00e9m-Par\u00e1: relato de caso","volume":"21","author":"PPdO Pardal","year":"2007"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1534\/genetics.106.056515","article-title":"Lachesis muta (Viperidae) cDNAs reveal diverging pit viper molecules and scaffolds typical of cobra (Elapidae) venoms: implications for snake toxin repertoire evolution","volume":"173","author":"IL Junqueira-de-Azevedo","year":"2006","journal-title":"Genetics"},{"issue":"28","key":"ref16","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.2174\/138161207782023784","article-title":"Trends in snakebite envenomation therapy: scientific, technological and public health considerations","volume":"13","author":"JM Guti\u00e9rrez","year":"2007","journal-title":"Curr Pharm Des"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0041-0101(01)00229-X","article-title":"Toxicity of South American snake venoms measured by an in vitro cell culture assay","volume":"40","author":"JC Oliveira","year":"2002","journal-title":"Toxicon"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.4062\/biomolther.2017.043","article-title":"Establishment of Immortalized Primary Human Foreskin Keratinocytes and Their Application to Toxicity Assessment and Three Dimensional Skin Culture Construction","volume":"25","author":"M Choi","year":"2017","journal-title":"Biomol Ther (Seoul)"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"OH LOWRY","year":"1951","journal-title":"J Biol Chem"},{"issue":"10","key":"ref20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3727\/096504009789735404","article-title":"Establishment and characterization of MACL-1 and MGSO-3 cell lines derived from human primary breast cancer","volume":"17","author":"CR Correa","year":"2009","journal-title":"Oncol Res"},{"issue":"9","key":"ref21","doi-asserted-by":"crossref","first-page":"12347","DOI":"10.3390\/s120912347","article-title":"Multiple applications of Alamar Blue as an indicator of metabolic function and cellular health in cell viability bioassays","volume":"12","author":"SN Rampersad","year":"2012","journal-title":"Sensors (Basel)"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1080\/14756360701810082","article-title":"A high density assay format for the detection of novel cytotoxic agents in large chemical libraries","volume":"23","author":"D Shum","year":"2008","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"2","key":"ref23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0022-1759(97)00043-4","article-title":"Assessment of the Alamar Blue assay for cellular growth and viability in vitro","volume":"204","author":"GR Nakayama","year":"1997","journal-title":"J Immunol Methods"},{"issue":"4","key":"ref24","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.etp.2017.01.001","article-title":"Montivipera bornmuelleri venom selectively exhibits high cytotoxic effects on keratinocytes cancer cell lines","volume":"69","author":"S Sawan","year":"2017","journal-title":"Exp Toxicol Pathol"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/sj.jid.5700049","article-title":"Role of matrix metalloproteinases in HaCaT keratinocytes apoptosis induced by loxosceles venom sphingomyelinase D","volume":"126","author":"D Paix\u00e3o-Cavalcante","year":"2006","journal-title":"J Invest Dermatol"},{"issue":"4","key":"ref26","doi-asserted-by":"crossref","first-page":"e0153090","DOI":"10.1371\/journal.pone.0153090","article-title":"Sphingomyelinase D from Loxosceles laeta Venom Induces the Expression of MMP7 in Human Keratinocytes: Contribution to Dermonecrosis","volume":"11","author":"MA Corr\u00eaa","year":"2016","journal-title":"PLoS One"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.3892\/ijmm.2015.2180","article-title":"Effects of bee venom against Propionibacterium acnes-induced inflammation in human keratinocytes and monocytes","volume":"35","author":"JY Kim","year":"2015","journal-title":"Int J Mol Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1042\/bse0390041","article-title":"Apoptosis: bombarding the mitochondria","volume":"39","author":"P Parone","year":"2003","journal-title":"Essays Biochem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"502676","DOI":"10.1155\/2014\/502676","article-title":"The impact of autophagy on cell death modalities","volume":"2014","author":"SW Ryter","year":"2014","journal-title":"Int J Cell Biol"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"DJ Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.toxicon.2015.11.013","article-title":"Understanding and confronting snakebite envenoming: The harvest of cooperation","volume":"109","author":"JM Guti\u00e9rrez","year":"2016","journal-title":"Toxicon"},{"issue":"10","key":"ref32","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":"N Jim\u00e9nez","year":"2008","journal-title":"J Invest Dermatol"},{"issue":"9\u201310","key":"ref33","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0300-9084(00)01163-9","article-title":"Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage","volume":"82","author":"JM Guti\u00e9rrez","year":"2000","journal-title":"Biochimie"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0014-4827(03)00183-6","article-title":"Activation of MMP-2, cleavage of matrix proteins, and adherens junctions during a snake venom metalloproteinase-induced endothelial cell apoptosis","volume":"288","author":"WB Wu","year":"2003","journal-title":"Exp Cell Res"},{"issue":"6","key":"ref35","doi-asserted-by":"crossref","first-page":"e727","DOI":"10.1371\/journal.pntd.0000727","article-title":"Mechanisms of vascular damage by hemorrhagic snake venom metalloproteinases: tissue distribution and in situ hydrolysis","volume":"4","author":"C Baldo","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"ref36","first-page":"249","article-title":"In vitro studies on Bothrops venoms cytotoxic effect on tumor cells","volume":"9","author":"RJ Jorge","year":"2011","journal-title":"J Exp Ther Oncol"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s10616-014-9820-2","article-title":"Evaluation of cytotoxic activities of snake venoms toward breast (MCF-7) and skin cancer (A-375) cell lines","volume":"68","author":"MJ Bradshaw","year":"2016","journal-title":"Cytotechnology"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1006\/taap.2002.9404","article-title":"Impairment of the cell-to-matrix adhesion and cytotoxicity induced by Bothrops moojeni snake venom in cultured renal tubular epithelia","volume":"181","author":"CB Collares-Buzato","year":"2002","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.toxicon.2016.04.040","article-title":"Bothrops erythromelas () venom induces apoptosis on renal tubular epithelial cells","volume":"118","author":"FC de Sousa","year":"2016","journal-title":"Toxicon"},{"issue":"5","key":"ref40","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1139\/O07-067","article-title":"Cytoskeletal rearrangement and cell death induced by Bothrops alternatus snake venom in cultured Madin-Darby canine kidney cells","volume":"85","author":"JM Nascimento","year":"2007","journal-title":"Biochem Cell Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.toxicon.2015.09.007","article-title":"Partial in vitro analysis of toxic and antigenic activities of eleven Peruvian pitviper snake venoms","volume":"108","author":"C Guerra-Duarte","year":"2015","journal-title":"Toxicon"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/toxsci\/kfv140","article-title":"Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays","volume":"147","author":"LL de Souza","year":"2015","journal-title":"Toxicol Sci"},{"issue":"12","key":"ref43","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/S0041-0101(98)00089-0","article-title":"Comparative study of the venoms of three subspecies of Lachesis muta (bushmaster) from Brazil, Colombia and Costa Rica","volume":"36","author":"R Otero","year":"1998","journal-title":"Toxicon"},{"key":"ref44","article-title":"The enigma of the north margin of the Amazon river: proven <italic>Lachesis<\/italic> bites in Brazil, report of two cases, general considerations about the genus and bibliographic review","author":"R Souza","year":"2007"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"S Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"issue":"5","key":"ref46","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1354\/vp.40-5-481","article-title":"The apoptosis-necrosis continuum: insights from genetically altered mice","volume":"40","author":"CJ Zeiss","year":"2003","journal-title":"Vet Pathol"},{"issue":"3","key":"ref47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrd3373","article-title":"Cell death assays for drug discovery","volume":"10","author":"O Kepp","year":"2011","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1152\/physrev.00013.2006","article-title":"Mitochondrial membrane permeabilization in cell death","volume":"87","author":"G Kroemer","year":"2007","journal-title":"Physiol Rev"},{"key":"ref49","doi-asserted-by":"crossref","DOI":"10.1177\/1179670717691251","article-title":"In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues","volume":"10","author":"B M\u00e9ry","year":"2017","journal-title":"J Cell Death"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijbiomac.2017.05.025","article-title":"A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities","volume":"103","author":"SEI Carone","year":"2017","journal-title":"Int J Biol Macromol"},{"issue":"3","key":"ref51","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/jcb.20322","article-title":"Characterization of events associated with apoptosis\/anoikis induced by snake venom metalloproteinase BaP1 on human endothelial cells","volume":"94","author":"C D\u00edaz","year":"2005","journal-title":"J Cell Biochem"},{"issue":"22","key":"ref52","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: process and function","volume":"21","author":"N Mizushima","year":"2007","journal-title":"Genes Dev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.toxicon.2016.08.004","article-title":"NKCT1 (purified Naja kaouthia protein toxin) conjugated gold nanoparticles induced Akt\/mTOR inactivation mediated autophagic and caspase 3 activated apoptotic cell death in leukemic cell","volume":"121","author":"T Bhowmik","year":"2016","journal-title":"Toxicon"},{"issue":"10","key":"ref54","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/aps.2014.62","article-title":"Crotoxin induces apoptosis and autophagy in human lung carcinoma cells in vitro via activation of the p38MAPK signaling pathway","volume":"35","author":"R Han","year":"2014","journal-title":"Acta Pharmacol Sin"},{"issue":"7","key":"ref55","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.toxicon.2012.08.008","article-title":"Isolation and biochemical, functional and structural characterization of a novel L-amino acid oxidase from Lachesis muta snake venom","volume":"60","author":"C Bregge-Silva","year":"2012","journal-title":"Toxicon"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/15569543.2016.1220397","article-title":"Toxin synergism in snake venoms","author":"AH Laustsen","year":"2016","journal-title":"Toxin Reviews"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0006427","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0006427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T20:48:52Z","timestamp":1660942132000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0006427"}},"subtitle":[],"editor":[{"given":"Juan J","family":"Calvete","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,4,16]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0006427","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0006427","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,16]]}}}