{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:04:46Z","timestamp":1778709886114,"version":"3.51.4"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2011\/23236-4"],"award-info":[{"award-number":["2011\/23236-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/06290-6"],"award-info":[{"award-number":["2015\/06290-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs\/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines\/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.<\/jats:p>","DOI":"10.3390\/biom10050794","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T11:31:18Z","timestamp":1590060678000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids"],"prefix":"10.3390","volume":"10","author":[{"given":"Marco Aurelio","family":"Sartim","sequence":"first","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-5270","authenticated-orcid":false,"given":"Camila O. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassiano Ricardo A. F.","family":"Diniz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-7142","authenticated-orcid":false,"given":"Vanessa M. B.","family":"da Fonseca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas O.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7252-1874","authenticated-orcid":false,"given":"Ana Paula F.","family":"Peti","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tassia Rafaella","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4005-157X","authenticated-orcid":false,"given":"Alan G.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Basic and Oral Biology, School of Dentistry of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-904, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos C.","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-9935","authenticated-orcid":false,"given":"Carlos A.","family":"Sorgi","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4999-8305","authenticated-orcid":false,"given":"Lucia Helena","family":"Faccioli","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3274-180X","authenticated-orcid":false,"given":"Suely Vilela","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.toxicon.2011.05.021","article-title":"Crotoxin and phospholipases A 2 from Crotalus durissus terrificus showed antiviral activity against dengue and yellow fever viruses","volume":"59","author":"Muller","year":"2012","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10760","DOI":"10.1038\/ncomms10760","article-title":"Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality","volume":"7","author":"Zoccal","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.toxicon.2012.12.003","article-title":"Inhibitory effect of Crotalus durissus terrificus venom on chronic edema induced by injection of bacillus Calmette-Gu\u00e9rin into the footpad of mice","volume":"63","author":"Sampaio","year":"2013","journal-title":"Toxicon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.biopsych.2013.04.009","article-title":"5-lipoxygenase activating protein reduction ameliorates cognitive deficit, synaptic dysfunction, and neuropathology in a mouse model of Alzheimer\u2019s disease","volume":"74","author":"Giannopoulos","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chaisakul, J., Ahmad 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_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.pbb.2008.08.016","article-title":"The analgesic effect of crotoxin on neuropathic pain is mediated by central muscarinic receptors and 5-lipoxygenase-derived mediators","volume":"91","author":"Amorim","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0041-0101(82)90062-9","article-title":"Protection by atropine against synergistic lethal effects of the Angusticeps-type toxin F7 from eastern green mamba venom and toxin I from black mamba venom","volume":"20","author":"Lee","year":"1982","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"H655","DOI":"10.1152\/ajpheart.00114.2015","article-title":"Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter","volume":"309","author":"Durand","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1476-5381.2009.00521.x","article-title":"Antidepressant-like effects of cannabidiol in mice: Possible involvement of 5-HT 1A receptors","volume":"159","author":"Zanelati","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","first-page":"e50062","article-title":"An in vivo assay to test blood vessel permeability","volume":"73","author":"Radu","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper\u2014Excel-based tool using pair-wise correlations","volume":"26","author":"Pfaffl","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"180167","DOI":"10.1038\/sdata.2018.167","article-title":"Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays","volume":"21","author":"Sorgi","year":"2018","journal-title":"Sci. Data"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"G593","DOI":"10.1152\/ajpgi.90431.2008","article-title":"IL-4 regulates susceptibility to intestinal inflammation in murine food allergy","volume":"296","author":"Cardoso","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.3389\/fimmu.2018.01970","article-title":"CD18 regulates monocyte hematopoiesis and promotes resistance to experimental schistosomiasis","volume":"9","author":"Souza","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.toxicon.2008.10.021","article-title":"Enzymatic and structural characterization of new PLA2 isoform isolated from white venom of Crotalus durissus ruruima","volume":"53","author":"Marangoni","year":"2009","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.taap.2017.08.021","article-title":"Neuromuscular paralysis by the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage","volume":"334","author":"Cavalcante","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_17","first-page":"1111","article-title":"Effects of crotoxin on the action potential kinetics of frog skeletal muscle","volume":"26","year":"1993","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_18","first-page":"1033","article-title":"Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA2, NSC-624244) in patients with advanced cancer","volume":"8","author":"Cura","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0041-0101(03)00037-0","article-title":"Inflammatory oedema induced by phospholipases A2 isolated from Crotalus durissus sp. in the rat dorsal skin: A role for mast cells and sensory C-fibers","volume":"41","author":"Esquisatto","year":"2003","journal-title":"Toxicon"},{"key":"ref_20","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":"Marangoni","year":"2008","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.toxicon.2008.06.012","article-title":"Secretory phospholipases A2 isolated from Bothrops asper and from Crotalus durissus terrificus snake venoms induce distinct mechanisms for biosynthesis of prostaglandins E2 and D2 and expression of cyclooxygenases","volume":"52","author":"Moreira","year":"2008","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0306-4522(03)00525-6","article-title":"Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons","volume":"121","author":"Wei","year":"2003","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.ijbiomac.2017.07.140","article-title":"Phospholipase A2 Inhibitor from Crotalus durissus terrificus rattlesnake: Effects on human peripheral blood mononuclear cells and human neutrophils cells","volume":"105","author":"Xavier","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0041-0101(85)90367-8","article-title":"Myonecrosis, myoglobinuria and acute renal failure induced by south american rattlesnake (Crotalus durissus terrificus) envenomation in brazil","volume":"23","author":"Cupo","year":"1985","journal-title":"Toxicon"},{"key":"ref_25","first-page":"27","article-title":"Rattlesnake bites. Clinical features and complementary tests","volume":"52","author":"Cupo","year":"1990","journal-title":"Mem. Inst. Butantan"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3109\/15563650.2013.802796","article-title":"Coagulopathy as the main systemic manifestation after envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus): Case report","volume":"51","author":"Bucaretchi","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0041-0101(83)90054-5","article-title":"Envenomation by the Mojave rattlesnake (Crotalus scutulatus scutulatus) in southern Arizona, USA","volume":"21","author":"Hardy","year":"1983","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1590\/S0036-46651991000400002","article-title":"Respiratory involvement secondary to crotalid ophidian bite (Crotalus durissus)","volume":"33","author":"Amaral","year":"1991","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0736-4679(01)00315-8","article-title":"Airway obstruction following canebrake rattlesnake envenomation","volume":"20","author":"Kerns","year":"2001","journal-title":"J. Emerg. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0736-4679(02)00573-5","article-title":"Respiratory compromise in patients with rattlesnake envenomation","volume":"23","author":"Brooks","year":"2002","journal-title":"J. Emerg. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.toxicon.2019.03.009","article-title":"Crotalus durissus terrificus (viperidae; crotalinae) envenomation: Respiratory failure and treatment with antivipmyn TRI \u00ae antivenom","volume":"163","author":"Baum","year":"2019","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0091-3057(99)00177-X","article-title":"Gabaergic-benzodiazepine system is involved in the crotoxin-induced anxiogenic effect","volume":"65","author":"Moreira","year":"2000","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1590\/S0004-27492012000500002","article-title":"Study of crotoxin on the induction of paralysis in extraocular muscle in animal model","volume":"75","author":"Velarde","year":"2012","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.toxicon.2004.03.011","article-title":"A comparative study of biological activities of crotoxin and CB fraction of venoms from Crotalus durissus terrificus, Crotalus durissus cascavella and Crotalus durissus collilineatus","volume":"43","author":"Lima","year":"2004","journal-title":"Toxicon"},{"key":"ref_35","first-page":"1000","article-title":"Pharmacology of crystalline crotoxin. 3. Cardiovascular and respiratory effects of crotoxin and Crotalus durissus terrificus venom","volume":"33","author":"Brazil","year":"1966","journal-title":"Mem. Inst. Butantan"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0035-9203(90)90358-L","article-title":"Acute myocardial infarction-like enzyme profile in human victims of Crotalus durissus terrificus envenoming","volume":"84","author":"Cupo","year":"1990","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/qjmed\/94.10.551","article-title":"Coagulopathy following lethal and non-lethal envenoming of humans by the South American rattlesnake (Crotalus durissus) in Brazil","volume":"94","year":"2001","journal-title":"QJM"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1191\/0960327103ht392oa","article-title":"Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus durissus terrificus snake venom in dogs","volume":"22","author":"Tomy","year":"2003","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_39","first-page":"981","article-title":"Pharmacology of crystalline crotoxin. II. Neuromuscular blocking action","volume":"33","author":"Brazil","year":"1966","journal-title":"Mem. Inst. Butantan"},{"key":"ref_40","unstructured":"Haschek, W.M., Rousseaux, C.G., Wallig, M.A., Bolon, B., and Ochoa, R. (2013). Haschek and Rousseaux\u2019s Handbook of Toxicologic Pathology, Elsevier. [3rd ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.pupt.2011.05.001","article-title":"Exploring lung physiology in health and disease with lung slices","volume":"24","author":"Sanderson","year":"2011","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.toxicon.2008.02.006","article-title":"Pulmonary mechanic and lung histology injury induced by Crotalus durissus terrificus snake venom","volume":"51","author":"Nonaka","year":"2008","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.toxicon.2017.07.023","article-title":"Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom","volume":"137","author":"Serra","year":"2017","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/cphy.c100013","article-title":"Acute lung injury and pulmonary vascular permeability: Use of transgenic models","volume":"1","author":"Parker","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/ncomms2774","article-title":"Control of lung vascular permeability and endotoxin-induced pulmonary oedema by changes in extracellular matrix mechanics","volume":"4","author":"Mammoto","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0952-3278(03)00070-X","article-title":"5-Lipoxygenase and FLAP","volume":"69","author":"Brock","year":"2003","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2017.07.012","article-title":"Biosynthesis of leukotriene B4","volume":"33","author":"Wan","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1194\/jlr.M002428","article-title":"Modulation of the activity of cytosolic phospholipase A2\u03b1 (cPLA2\u03b1) by cellular sphingolipids and inhibition of cPLA2\u03b1 by sphingomyelin","volume":"51","author":"Nakamura","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0952-3278(91)90146-V","article-title":"The antiinflammatory agent SC-41930 inhibits granulocyte infiltration of the rodent dermis induced by 6-trans-leukotriene B4","volume":"44","author":"Fretland","year":"1991","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4049\/jimmunol.1101029","article-title":"Regulation of immune responses by prostaglandin E 2","volume":"188","author":"Kalinski","year":"2012","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bbalip.2014.10.008","article-title":"Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid","volume":"1851","author":"Powell","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.smim.2017.09.009","article-title":"LTB4 and BLT1 in inflammatory arthritis","volume":"33","author":"Miyabe","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1111\/bph.12815","article-title":"Multiple roles of the PGE2-EP receptor signal in vascular permeability","volume":"171","author":"Omori","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1136\/thx.37.12.918","article-title":"Dual effect of prostaglandm E2 on normal airways smooth muscle in vivo","volume":"37","author":"Walters","year":"1982","journal-title":"Thorax"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1038\/s41598-017-04498-8","article-title":"A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages","volume":"7","author":"Giannotti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.toxicon.2005.11.008","article-title":"Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis","volume":"47","author":"Sampaio","year":"2006","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"De Almeida, C.S., Andrade-Oliveira, V., C\u00e2mara, N.O.S., Jacysyn, J.F., and Faquim-Mauro, E.L. (2015). Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121427"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pulli, B., Ali, M., Forghani, R., Schob, S., Hsieh, K.L.C., Wojtkiewicz, G., Linnoila, J.J., and Chen, J.W. (2013). Measuring myeloperoxidase activity in biological samples. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067976"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0041-0101(86)90178-9","article-title":"Muscle necrosis caused by the sub-units of crotoxin","volume":"24","author":"Kouyoumdjian","year":"1986","journal-title":"Toxicon"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1476-5381.1995.tb17178.x","article-title":"Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2","volume":"114","author":"Landucci","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/09629350124986","article-title":"Role of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus snake venom, on inflammatory and immune reactions","volume":"10","author":"Cardoso","year":"2001","journal-title":"Mediat. Inflamm."},{"key":"ref_62","first-page":"440","article-title":"Legionella longbeachae is immunologically silent and highly virulent in vivo","volume":"215","author":"Massis","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1002\/cphy.c100067","article-title":"Mechanics of the lung in the 20th century","volume":"1","author":"Mitzner","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1152\/physrev.00019.2007","article-title":"Lung parenchymal mechanics in health and disease","volume":"89","author":"Faffe","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"McGovern, T.K., Robichaud, A., Fereydoonzad, L., Schuessler, T.F., and Martin, J.G. (2013). Evaluation of respiratory system mechanics in mice using the forced oscillation technique. J. Vis. Exp., e50172.","DOI":"10.3791\/50172"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1186\/cc3516","article-title":"Clinical review: Respiratory mechanics in spontaneous and assisted ventilation","volume":"9","author":"Grinnan","year":"2005","journal-title":"Crit. Care"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40248-017-0084-5","article-title":"The physiological basis and clinical significance of lung volume measurements","volume":"12","author":"Lutfi","year":"2017","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"L919","DOI":"10.1152\/ajplung.00183.2015","article-title":"Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis","volume":"310","author":"Fernandez","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Vulfius, C.A., Kasheverov, I.E., Kryukova, E.V., Spirova, E.N., Shelukhina, I.V., Starkov, V.G., Andreeva, T.V., Faure, G., Zouridakis, M., and Tsetlin, V.I. (2017). Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186206"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0306-4522(79)90090-3","article-title":"Changes in spontaneous and evoked release of transmitter induced by the crotoxin complex and its component phospholipase A2 at the frog neuromuscular junction","volume":"4","author":"Hawgood","year":"1979","journal-title":"Neuroscience"},{"key":"ref_71","first-page":"33","article-title":"Nature of the postsynaptic action of crotoxin at guinea-pig diaphragm end-plates","volume":"9","author":"Brazil","year":"2000","journal-title":"J. Nat. Toxins"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0041-0101(90)90415-4","article-title":"Effects of crotoxin on the isolated guinea pig heart","volume":"28","author":"Santos","year":"1990","journal-title":"Toxicon"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/0028-3908(89)90160-3","article-title":"The effect of crotoxin on the longitudinal muscle-myenteric plexus preparation of the guinea pig ileum","volume":"28","author":"Muniz","year":"1989","journal-title":"Neuropharmacology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0005-2760(89)90194-X","article-title":"Binding of divalent and trivalent cations with crotoxin and with its phospholipase and its non-catalytic subunits: Effects on enzymatic activity and on the interaction of phospholipase component with phospholipids","volume":"1006","author":"Radvanyi","year":"1989","journal-title":"Biochim. Biophys. Acta (BBA) Lipids Lipid Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1021\/bi00112a015","article-title":"Identification of a new binding protein for crotoxin and other neurotoxic phospholipase A 2 s on brain synaptic membranes","volume":"30","author":"Yen","year":"1991","journal-title":"Biochemistry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/head.12769","article-title":"The Pharmacology of Indomethacin","volume":"56","author":"Lucas","year":"2016","journal-title":"Headache"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1476-5381.1984.tb10801.x","article-title":"The channel-blocking action of methonium compounds on rat submandibular ganglion cells","volume":"82","author":"Gurney","year":"1984","journal-title":"Br. J. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1476-5381.1984.tb10105.x","article-title":"The interaction between hexamethonium and tubocurarine on the rat neuromuscular junction","volume":"81","author":"Rang","year":"1984","journal-title":"Br. J. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.etp.2007.04.002","article-title":"Alterations in the ultrastructure of cardiac autonomic nervous system triggered by crotoxin from rattlesnake (Crotalus durissus cumanensis) venom","volume":"59","author":"Scannone","year":"2007","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF00517389","article-title":"Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin","volume":"292","author":"Breithaupt","year":"1976","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.rmed.2010.10.020","article-title":"The lung permeability index: A feasible measurement of pulmonary capillary permeability","volume":"105","author":"Huaringa","year":"2011","journal-title":"Respir. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/BF00499666","article-title":"Biochemistry and pharmacology of the crotoxin complex-II. Possible interrelationships between toxicity and organ distribution of phospholipase A, crotapotin and their combination","volume":"273","author":"Habermann","year":"1972","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_83","unstructured":"Soares, M.A., Silveira, M.B., Simal, C., Forte-Dias, C.L., and dos Santos, R.G. (October, January 27). Biodistibution and spect imaging of crotoxin on mice bearing Ehrlich tumor. Proceedings of the International Nuclear Atlantic Conference, Aben, Associa\u00e7\u00e3o Brasileira De Energia Nuclear, Rio de Janeiro, Brazil."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40409-018-0178-3","article-title":"Immunotherapeutic potential of Crotoxin: Anti-inflammatory and immunosuppressive properties","volume":"24","author":"Sartim","year":"2018","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/aps.2009.88","article-title":"Central cholinergic regulation of respiration: Nicotinic receptors","volume":"30","author":"Shao","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000336498","article-title":"Role of parasympathetic nerves and muscarinic receptors in allergy and asthma","volume":"98","author":"Scott","year":"2012","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jnnp.56.4.334","article-title":"Acute neuromuscular respiratory paralysis","volume":"56","author":"Hughes","year":"1993","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1089\/ars.2007.1574","article-title":"Hypoxia and the lung: Beyond hypoxic vasoconstriction","volume":"9","author":"Nicolls","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"856918","DOI":"10.1155\/2012\/856918","article-title":"Lung oxidative damage by hypoxia","volume":"2012","author":"Araneda","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.toxicon.2013.07.019","article-title":"Antinociceptive activity of crotoxin in the central nervous system: A functional Magnetic Resonance Imaging study","volume":"74","author":"Esser","year":"2013","journal-title":"Toxicon"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.3892\/mmr.2014.2620","article-title":"Crotoxin suppresses the tumorigenic properties and enhances the antitumor activity of Iressa\u00ae (gefinitib) in human lung adenocarcinoma SPCA-1 cells","volume":"10","author":"Wang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.toxicon.2018.10.306","article-title":"Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines","volume":"156","author":"Muller","year":"2018","journal-title":"Toxicon"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.conctc.2017.07.008","article-title":"Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study","volume":"7","author":"Medioni","year":"2017","journal-title":"Contemp. Clin. Trials Commun."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/794\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:30:54Z","timestamp":1760175054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":93,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["biom10050794"],"URL":"https:\/\/doi.org\/10.3390\/biom10050794","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,20]]}}}