Journal of Venomous Animals and Toxins Including Tropical Diseases最新文献

{"title":"A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy","authors":"D. Buchaim, J. Andreo, K. T. Pomini, B. Barraviera, R. S. Ferreira, M. H. Duarte, M. Alcalde, Carlos Henrique Bertoni Reis, Daniel de Bortoli Teixeira, C. R. Bueno, C. Detregiachi, A. Araújo, R. Buchaim","doi":"10.1590/1678-9199-JVATITD-2021-0056","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0056","url":null,"abstract":"Abstract Background: The association of scaffolds to repair extensive bone defects can contribute to their evolution and morphophysiological recomposition. The incorporation of particulate biomaterials into three-dimensional fibrin bioproducts together with photobiomodulation therapy (PBM) has potential and can improve regenerative medicine procedures. The objective of this experiment was to evaluate the effects of PBM therapy on critical size defects filled with xenogenic bone substitute associated with fibrin biopolymer. Methods: A critical defect of 8 mm was performed in 36 Wistar male adult rats that were divided into four groups. Groups BC and BC-PBM were defined as controls with defects filled by a clot (without or with PBM, respectively) and groups XS and XS-PBM that comprised those filled with biocomplex Bio-OssTM in association with fibrin biopolymer. PBM was applied immediately after the surgery and three times a week every other day, with the parameters: wavelength of 830 nm, energy density 6.2 J/cm2, output power 30 mW, beam area of 0.116 cm2, irradiance 0.258,62 W/cm2, energy/point 0.72 J, total energy 2.88 J. Fourteen and 42 days after the surgery, animals were euthanatized and subjected to microtomography, qualitative and quantitative histological analysis. Results: The BC-PBM and XS-PBM groups had a similar evolution in the tissue repair process, with a higher density of the volume of new formed bone in relation to the groups without PBM (p = 0.04086; p = 0.07093, respectively). Intense vascular proliferation and bone deposition around the biomaterial particles were observed in the animals of the groups in which biocomplex was applied (XS and XS-PBM). Conclusion: PBM therapy allowed an improvement in the formation of new bone, with a more organized deposition of collagen fibers in the defect area. Biocomplex favored the insertion and permanence of the particulate material in bone defects, creating a favorable microenvironment for accelerate repair process.","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"64 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84258123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voracity, reaction to stings, and survival of domestic hens when feeding on the yellow scorpion (Tityus serrulatus)","authors":"G. P. Murayama, G. F. Pagoti, J. Guadanucci, R. Willemart","doi":"10.1590/1678-9199-JVATITD-2021-0050","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0050","url":null,"abstract":"Abstract Background: Scorpionism is a worldwide problem that has already made thousands of victims, and multi-disciplinary approaches for controlling their populations are to be more successful. Hens are often mentioned as tools for controlling scorpions; however, systematic/experimental behavioral studies are not available. Moreover, there is no systematic information on the effect of scorpion venoms on hens. Using the venomous yellow scorpion Tityus serrulatus, the present study aimed to clarify the following aspects: (1) voracity of hens, (2) how hens react when stung, (3) the effect of scorpion stings on hen behavior during attacks, and (4) hen survivorship after feeding on scorpions. Methods: We attracted hens with corn powder, offered them scorpions and then recorded the hen-scorpion interaction. To test the effects of the sting we manually removed the scorpion’s telson. Results: We found that some hens ate up to six scorpions within minutes. By means of an ethogram and drawings, we showed that they exhibited several aversive behaviors when capturing scorpions. Removal of the scorpion telson stopped the aversive reactions, which was not observed in the control group. Finally, hens did not exhibit atypical behaviors after 1, 7 and 30 days and were all alive after 30 days. Conclusion: This is the first empirical and video recorded study providing evidence that hens are clearly affected by scorpion venom but do not die. Therefore, they may have potential to be used in biological control of these arthropods.","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74997331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative venomic profiles of three spiders of the genus Phoneutria","authors":"Frederico Francisco Fernandes, Juliana Rodrigues Moraes, Jaqueline Leal Dos Santos, Thiago G Soares, Vitor José Pinto Gouveia, Alessandra Matavel, W. C. Borges, M. N. Cordeiro, S. Figueiredo, M. H. Borges","doi":"10.1590/1678-9199-JVATITD-2021-0042","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0042","url":null,"abstract":"Abstract Background: Spider venoms induce different physio-pharmacological effects by binding with high affinity on molecular targets, therefore being of biotechnological interest. Some of these toxins, acting on different types of ion channels, have been identified in the venom of spiders of the genus Phoneutria, mainly from P. nigriventer. In spite of the pharmaceutical potential demonstrated by P. nigriventer toxins, there is limited information on molecules from venoms of the same genus, as their toxins remain poorly characterized. Understanding this diversity and clarifying the differences in the mechanisms of action of spider toxins is of great importance for establishing their true biotechnological potential. This prompted us to compare three different venoms of the Phoneutria genus: P. nigriventer (Pn-V), P. eickstedtae (Pe-V) and P. pertyi (Pp-V). Methods: Biochemical and functional comparison of the venoms were carried out by SDS-PAGE, HPLC, mass spectrometry, enzymatic activities and electrophysiological assays (whole-cell patch clamp). Results: The employed approach revealed that all three venoms had an overall similarity in their components, with only minor differences. The presence of a high number of similar proteins was evident, particularly toxins in the mass range of ~6.0 kDa. Hyaluronidase and proteolytic activities were detected in all venoms, in addition to isoforms of the toxins Tx1 and Tx2-6. All Tx1 isoforms blocked Nav1.6 ion currents, with slight differences. Conclusion: Our findings showed that Pn-V, Pe-V and Pp-V are highly similar concerning protein composition and enzymatic activities, containing isoforms of the same toxins sharing high sequence homology, with minor modifications. However, these structural and functional variations are very important for venom diversity. In addition, our findings will contribute to the comprehension of the molecular diversity of the venoms of the other species from Phoneutria genus, exposing their biotechnological potential as a source for searching for new active molecules.","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"33 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81038879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant expression and antigenicity of two peptide families of neurotoxins from <i>Androctonus</i> sp.","authors":"Samuel Cardoso-Arenas,&nbsp;Herlinda Clement,&nbsp;Iván Arenas,&nbsp;Felipe Olvera,&nbsp;Fernando Zamudio,&nbsp;Figen Caliskan,&nbsp;Ligia Luz Corrales-García,&nbsp;Gerardo Corzo","doi":"10.1590/1678-9199-JVATITD-2022-0026","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0026","url":null,"abstract":"<p><strong>Background: </strong>Scorpion neurotoxins such as those that modify the mammalian voltage-gated sodium ion channels (Nav) are the main responsible for scorpion envenomation. Their neutralization is crucial in the production of antivenoms against scorpion stings.</p><p><strong>Methods: </strong>In the present study, two <i>in silico</i> designed genes - one that codes for a native neurotoxin from the venom of the Anatolian scorpion <i>Androctonus crassicauda,</i> named Acra 4 - and another non-native toxin - named consensus scorpion toxin (SccTx) obtained from the alignment of the primary structures of the most toxic neurotoxins from the Middle Eastern and North African scorpions - were recombinantly expressed in <i>E. coli</i> Origami.</p><p><strong>Results: </strong>Following bacterial expression, the two expressed neurotoxins, hereafter named HisrAcra4 and HisrSccTx, were obtained from inclusion bodies. Both recombinant neurotoxins were obtained in multiple Cys-Cys isoforms. After refolding, the active protein fractions were identified with molecular masses of 8,947.6 and 9,989.1 Da for HisrAcra4 and HisrSccTx, respectively, which agreed with their expected theoretical masses. HisrAcra4 and HisrSccTx were used as antigens to immunize two groups of rabbits, to produce either anti-HisrAcra4 or anti-HisrSccTx serum antibodies, which in turn could recognize and neutralize neurotoxins from venoms of scorpion species from the Middle East and North Africa. The antibodies obtained from rabbits neutralized the 3LD₅₀ of <i>Androctonus australis, Leiurus quinquestriatus hebraeus</i> and <i>Buthus occitanus</i> venoms, but they did not neutralize <i>A. crassicauda</i> and <i>A. mauritanicus</i> venoms. In addition, the anti-HisrAcra4 antibodies did not neutralize any of the five scorpion venoms tested. However, an antibody blend of anti-HisrAcra4 and anti-HisrSccTx was able to neutralize <i>A. crassicauda</i> and <i>A. mauritanicus</i> venoms.</p><p><strong>Conclusions: </strong>Two recombinant Nav neurotoxins, from different peptide families, were used as antigens to generate IgGs for neutralizing scorpion venoms of species from the Middle East and North Africa.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"28 ","pages":"e20220026"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospecting for candidate molecules from <i>Conus virgo</i> toxins to develop new biopharmaceuticals.","authors":"Anas A Mohamed,&nbsp;Zohour I Nabil,&nbsp;Mohamed S El-Naggar","doi":"10.1590/1678-9199-JVATITD-2022-0028","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0028","url":null,"abstract":"<p><strong>Background: </strong>A combination of pharmacological and biomedical assays was applied in this study to examine the bioactivity of <i>Conus virgo</i> crude venom in order to determine the potential pharmacological benefit of this venom, and its <i>in vivo</i> mechanism of action.</p><p><strong>Methods: </strong>Two doses (1/5 and 1/10 of LC₅₀, 9.14 and 4.57 mg/kg) of the venom were used in pharmacological assays (central and peripheral analgesic, anti-inflammatory and antipyretic), while 1/2 of LC₅₀ (22.85 mg/kg) was used in cytotoxic assays on experimental animals at different time intervals, and then compared with control and reference drug groups.</p><p><strong>Results: </strong>The tail immersion time was significantly increased in venom-treated mice compared with the control group. Also, a significant reduction in writhing movement was recorded after injection of both venom doses compared with the control group. In addition, only the high venom concentration has a mild anti-inflammatory effect at the late inflammation stage. The induced pyrexia was also decreased significantly after treatment with both venom doses. On the other hand, significant increases were observed in lipid peroxidation (after 4 hours) and reduced glutathione contents and glutathione peroxidase activity, while contents of lipid peroxidation and nitric oxide (after 24 hours) and catalase activity were depleted significantly after venom administration.</p><p><strong>Conclusion: </strong>These results indicated that the crude venom of <i>Conus virgo</i> probably contain bioactive components that have pharmacological activities with low cytotoxic effects. Therefore, it may comprise a potential lead compound for the development of drugs that would control pain and pyrexia.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"28 ","pages":"e20220028"},"PeriodicalIF":2.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10481729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent interstitial lung abnormalities in post-COVID-19 patients: a case series.","authors":"Vanessa Carvalho Lago,&nbsp;Robson Aparecido Prudente,&nbsp;Dayane Araujo Luzia,&nbsp;Estefânia Thomé Franco,&nbsp;Talita Jacon Cezare,&nbsp;Amanda Peralta,&nbsp;Eloara Vieira M Ferreira,&nbsp;André Luis Pereira Albuquerque,&nbsp;Marina Politi Okoshi,&nbsp;Bruno Guedes Baldi,&nbsp;Suzana Erico Tanni","doi":"10.1590/1678-9199-JVATITD-2020-0157","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0157","url":null,"abstract":"<p><p>A new concept of multisystem disease has emerged as a long-term condition following mild-severe COVID-19 infection. The main symptoms of this affection are breathlessness, chest pain, and fatigue. We present here the clinical case of four COVID-19 patients during hospitalization and 60 days after hospital discharge. Physiological impairment of all patients was assessed by spirometry, dyspnea score, arterial blood gas, and 6-minute walk test 60 days after hospital discharge, and computed tomographic scan 90 days after discharge. All patients had fatigue, which was not related to hypoxemia or impaired spirometry values, and interstitial lung alterations, which occurred in both mechanically ventilated and non-mechanically ventilated patients. In conclusion, identifying the prevalence and patterns of permanent lung damage is paramount in preventing and treating COVID-19-induced fibrotic lung disease. Additionally, and based on our preliminary results, it will be also relevant to establish long-term outpatient programs for these individuals.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"27 ","pages":"e20200157"},"PeriodicalIF":2.4,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region.","authors":"Manuela B Pucca,&nbsp;Michelle V S Franco,&nbsp;Jilvando M Medeiros,&nbsp;Isadora S Oliveira,&nbsp;Shirin Ahmadi,&nbsp;Felipe A Cerni,&nbsp;Umberto Zottich,&nbsp;Bruna K Bassoli,&nbsp;Wuelton M Monteiro,&nbsp;Andreas H Laustsen","doi":"10.1590/1678-9199-JVATITD-2020-0083","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0083","url":null,"abstract":"<p><strong>Background: </strong>Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The <i>Bothrops</i> (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. <i>Bothrops</i> spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied.</p><p><strong>Case presentation: </strong>Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the <i>Bothrops</i> genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming.</p><p><strong>Conclusion: </strong>In Latin America, especially in Brazil, where there is a high prevalence of <i>Bothrops</i> envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200083"},"PeriodicalIF":2.4,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38805602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hello, kitty: could cat allergy be a form of intoxication?","authors":"Rodrigo Ligabue-Braun","doi":"10.1590/1678-9199-JVATITD-2020-0051","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0051","url":null,"abstract":"<p><strong>Background: </strong>The relationship between slow loris (<i>Nycticebus</i> spp.) venom (BGE protein) and the major cat allergen (Fel d 1) from domestic cat (<i>Felis catus</i>) is known for about two decades. Along this time, evidence was accumulated regarding convergences between them, including their almost identical mode of action.</p><p><strong>Methods: </strong>Large-scale database mining for Fel d 1 and BGE proteins in Felidae and <i>Nycticebus</i> spp., alignment, phylogeny proposition and molecular modelling, associated with directed literature review were assessed.</p><p><strong>Results: </strong>Fel d 1 sequences for 28 non-domestic felids were identified, along with two additional loris BGE protein sequences. Dimer interfaces are less conserved among sequences, and the chain 1 shows more sequence similarity than chain 2. Post-translational modification similarities are highly probable.</p><p><strong>Conclusions: </strong>Fel d 1 functions beyond allergy are discussed, considering the great conservation of felid orthologs of this protein. Reasons for toxicity being found only in domestic cats are proposed in the context of domestication. The combination of the literature review, genome-derived sequence data, and comparisons with the venomous primate slow loris may point to domestic cats as potentially poisonous mammals.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200051"},"PeriodicalIF":2.4,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38827590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of <i>Bitis gabonica</i> and <i>Dendroaspis angusticeps</i> snake venoms on apoptosis-related genes in human thymic epithelial cells.","authors":"Francisc Boda,&nbsp;Krisztina Banfai,&nbsp;Kitti Garai,&nbsp;Bela Kovacs,&nbsp;Attila Almasi,&nbsp;Dalma Scheffer,&nbsp;Reka Lambertne Sinkler,&nbsp;Robert Csonka,&nbsp;Tamas Czompoly,&nbsp;Krisztian Kvell","doi":"10.1590/1678-9199-JVATITD-2020-0057","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0057","url":null,"abstract":"<p><strong>Background: </strong>Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from <i>Bitis gabonica</i> and <i>Dendroaspis angusticeps.</i></p><p><strong>Methods: </strong>Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 μg/mL (as used in previous TaqMan Array study). Gene expressional changes restricted to apoptosis were assayed by TaqMan Array (Human Apoptosis Plate).</p><p><strong>Results: </strong>The most prominent gene expressional changes were shown by <i>CASP5</i> (≈ 2.5 million-fold, confirmed by dedicated quantitative polymerase chain reaction) and <i>CARD9</i> (0.016-fold) for <i>B. gabonica,</i> and <i>BIRC7</i> (6.46-fold) and <i>CASP1</i> (0.30-fold) for <i>D. angusticeps.</i></p><p><strong>Conclusion: </strong>The observed apoptotic environment suggests that pyroptosis may be the dominant pathway through which <i>B. gabonica</i> and <i>D. angusticeps</i> snake venoms trigger thymic epithelial apoptosis following envenomation.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200057"},"PeriodicalIF":2.4,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38784793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Bothrops moojeni</i> L-amino acid oxidase induces apoptosis and epigenetic modulation on Bcr-Abl⁺ cells.","authors":"Sandra Mara Burin,&nbsp;Maira da Costa Cacemiro,&nbsp;Juçara Gastaldi Cominal,&nbsp;Rone Aparecido De Grandis,&nbsp;Ana Rita Thomazela Machado,&nbsp;Flavia Sacilotto Donaires,&nbsp;Adelia Cristina Oliveira Cintra,&nbsp;Luciana Ambrosio,&nbsp;Lusânia Maria Greggi Antunes,&nbsp;Suely Vilela Sampaio,&nbsp;Fabíola Attié de Castro","doi":"10.1590/1678-9199-JVATITD-2020-0123","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0123","url":null,"abstract":"<p><strong>Background: </strong>Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Abl⁺ leukemic cells and improve the disease treatment.</p><p><strong>Methods: </strong>In the present study, we investigated whether the L-amino acid oxidase isolated from <i>Bothrops moojeni</i> snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Abl⁺ cell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression <i>in vitro</i>.</p><p><strong>Results: </strong>BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes <i>BID</i> and <i>FADD</i> and downregulated <i>DFFA</i> expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene <i>BCL2</i> - in Bcr-Abl⁺ cells.</p><p><strong>Conclusion: </strong>BmooLAAO-I exerts selective antitumor action mediated by H₂O₂ release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on <i>in vivo</i> models to determine its potential in CML therapy.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200123"},"PeriodicalIF":2.4,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38743465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}