{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:21:36Z","timestamp":1794277296109,"version":"4.9.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Mashhad University of Medical Sciences, Iran, Islamic Republic Of","award":["981318"],"award-info":[{"award-number":["981318"]}],"id":[{"id":"https:\/\/ror.org\/04sfka033","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Melittin is one of the most studied antimicrobial peptides, and several\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the first step,\n                      <jats:italic>in vitro<\/jats:italic>\n                      toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB\/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR)\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      , methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (MRSA), and KPC-producing\n                      <jats:italic>Klebsiella pneumonia<\/jats:italic>\n                      (KPC-KP) pathogens were tested using both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Melittin showed extensive hemolysis (HD\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u20090.44\u00a0\u00b5g\/mL), and cytotoxicity (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u20096.45\u00a0\u00b5g\/mL) activities with i.p. LD\n                      <jats:sub>50<\/jats:sub>\n                      value of 4.98\u00a0mg\/kg in BALB\/c mice.\n                      <jats:italic>In vitro<\/jats:italic>\n                      antimicrobial evaluation showed melittin MIC range from 8 to 32\u00a0\u00b5g\/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4\u00a0mg\/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-021-00503-z","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T16:02:37Z","timestamp":1626278557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria"],"prefix":"10.1186","volume":"22","author":[{"given":"Parvin","family":"Askari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hasan","family":"Namaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiarash","family":"Ghazvini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"503_CR1","first-page":"1","volume-title":"Drug Discovery Targeting Drug-Resistant Bacteria","author":"R Thakare","year":"2020","unstructured":"Thakare R, Kesharwani P, Dasgupta A, Srinivas N, Chopra S. Antibiotics: past, present, and future. In: Kesharwani P, Chopra S, Dasgupta A, editors. Drug Discovery Targeting Drug-Resistant Bacteria. London: Acedemic press; 2020. p.\u00a01\u20138."},{"key":"503_CR2","doi-asserted-by":"crossref","unstructured":"Shakoor S, Warraich HJ, Zaidi AK. Infection Prevention and Control in the Tropics. In: Ryan ET, Hill DR, Solomon T, Endy TP, Aronson N, editors. Hunter\u2019s Tropical Medicine and Emerging Infectious Diseases. 10th ed. Canda:Elsevier; 2020. p.\u00a0159\u201365.","DOI":"10.1016\/B978-0-323-55512-8.00020-X"},{"key":"503_CR3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/CCM.0000000000004371","volume":"48","author":"SS Kadri","year":"2020","unstructured":"Kadri SS. Key Takeaways From the US CDC\u2019s 2019 Antibiotic Resistance Threats Report for Frontline Providers. Crit Care Med. 2020; 48:939\u2013945.","journal-title":"Crit Care Med"},{"key":"503_CR4","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1186\/s12879-019-4295-6","volume":"19","author":"M Mhondoro","year":"2019","unstructured":"Mhondoro M, Ndlovu N, Bangure D, Juru T, Gombe NT, Shambira G, et al. Trends in antimicrobial resistance of bacterial pathogens in Harare, Zimbabwe, 2012\u20132017: a secondary dataset analysis. BMC Infect Dis. 2019;19: 746.","journal-title":"BMC Infect Dis"},{"key":"503_CR5","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"AP Magiorakos","year":"2012","unstructured":"Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268\u201381.","journal-title":"Clin Microbiol Infect"},{"key":"503_CR6","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.3389\/fmicb.2020.01669","volume":"11","author":"A Le\u00f3n-Buitimea","year":"2020","unstructured":"Le\u00f3n-Buitimea A, Garza-C\u00e1rdenas CR, Garza-Cervantes JA, Lerma-Escalera JA, Morones-Ram\u00edrez JR. The Demand for New Antibiotics: Antimicrobial Peptides, Nanoparticles, and Combinatorial Therapies as Future Strategies in Antibacterial Agent Design. Front Microbiol. 2020;11:1699.","journal-title":"Front Microbiol"},{"key":"503_CR7","doi-asserted-by":"publisher","unstructured":"Chen CH, Lu TK. Development and Challenges of Antimicrobial Peptides for Therapeutic Applications. Antibiotics (Basel, Switzerland). 2020;9(1):24.https:\/\/doi.org\/10.3390\/antibiotics9010024","DOI":"10.3390\/antibiotics9010024"},{"key":"503_CR8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/biom10020247","volume":"10","author":"M Ceremuga","year":"2020","unstructured":"Ceremuga M, Stela M, Janik E, Gorniak L, Synowiec E, Sliwinski T et al. Melittin\u2014A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells. Biomolecules. 2020;10:247.","journal-title":"Biomolecules"},{"key":"503_CR9","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1179\/1973947812Y.0000000007","volume":"24","author":"S Dosler","year":"2012","unstructured":"Dosler S, Gerceker AA. In vitro activities of antimicrobial cationic peptides; melittin and nisin, alone or in combination with antibiotics against Gram-positive bacteria. J chemother. 2012;24:137\u201343.","journal-title":"J chemother"},{"key":"503_CR10","doi-asserted-by":"publisher","first-page":"105592","DOI":"10.1016\/j.ejps.2020.105592","volume":"156","author":"WG Lima","year":"2020","unstructured":"Lima WG, de Brito JCM, Cardoso VN, Fernandes SOA. In-depth characterization of antibacterial activity of melittin against Staphylococcus aureus and use in a model of non-surgical MRSA-infected skin wounds. Euro J of Pharm Sci. 2020;156:105592.","journal-title":"Euro J of Pharm Sci"},{"key":"503_CR11","doi-asserted-by":"publisher","first-page":"3265","DOI":"10.1007\/s00253-019-09698-y","volume":"103","author":"H Memariani","year":"2019","unstructured":"Memariani H, Memariani M, Shahidi-Dadras M, Nasiri S, Akhavan MM, Moravvej H. Melittin: from honeybees to superbugs. Appl Microbiol Biotechnol. 2019;103:3265\u201376.","journal-title":"Appl Microbiol Biotechnol"},{"key":"503_CR12","doi-asserted-by":"publisher","first-page":"6483","DOI":"10.3892\/mmr.2015.4275","volume":"12","author":"JH Choi","year":"2015","unstructured":"Choi JH, Jang AY, Lin S, Lim S, Kim D, Park K et al. Melittin, a honeybee venom\u2013derived antimicrobial peptide, may target methicillin\u2013resistant Staphylococcus aureus. Mol Med Rep. 2015;12:6483\u201390.","journal-title":"Mol Med Rep"},{"key":"503_CR13","doi-asserted-by":"publisher","first-page":"55042","DOI":"10.1074\/jbc.M408881200","volume":"279","author":"N Asthana","year":"2004","unstructured":"Asthana N, Yadav SP, Ghosh JK. Dissection of antibacterial and toxic activity of Melittin a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity. J Biol Chem. 2004; 279:55042\u201350.","journal-title":"J Biol Chem"},{"key":"503_CR14","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.toxicon.2015.12.005","volume":"110","author":"G Gajski","year":"2016","unstructured":"Gajski G, Domijan A-M, \u017degura B, \u0160tern A, Geri\u0107 M, Jovanovi\u0107 IN et al. Melittin induced cytogenetic damage, oxidative stress and changes in gene expression in human peripheral blood lymphocytes. Toxicon. 2016;110:56\u201367.","journal-title":"Toxicon"},{"key":"503_CR15","doi-asserted-by":"publisher","first-page":"100900","DOI":"10.1016\/j.genrep.2020.100900","volume":"21","author":"K Moridi","year":"2020","unstructured":"Moridi K, Hemmaty M, Eidgahi MRA, Najafi MF, Zare H, Ghazvini K et al. Construction, cloning, and expression of Melittin antimicrobial peptide using Pichia pastoris expression system. Gene Rep. 2020;21:100900.","journal-title":"Gene Rep"},{"key":"503_CR16","doi-asserted-by":"publisher","first-page":"3427","DOI":"10.31557\/APJCP.2018.19.12.3427","volume":"19","author":"C Tipgomut","year":"2018","unstructured":"Tipgomut C, Wongprommoon A, Takeo E, Ittiudomrak T, Puthong S, Chanchao C. Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour-Associated Macrophages. Asian Pac J Cancer Prev. 2018;19:3427.","journal-title":"Asian Pac J Cancer Prev"},{"key":"503_CR17","doi-asserted-by":"publisher","unstructured":"Evans BC, Nelson CE, Shann SY, Beavers KR, Kim AJ, Li H et al. Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J Vis Exp. 2013(73):e50166. https:\/\/doi.org\/10.3791\/50166.","DOI":"10.3791\/50166"},{"key":"503_CR18","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1111\/bph.15193","volume":"177","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Br J Pharmacol. 2020;177:3617\u201324.","journal-title":"Br J Pharmacol"},{"key":"503_CR19","doi-asserted-by":"publisher","unstructured":"Nagarajan D, Roy N, Kulkarni O, Nanajkar N, Datey A, Ravichandran S et al. \u03a976: A designed antimicrobial peptide to combat carbapenem-and tigecycline-resistant Acinetobacter baumannii. Sci adv. 2019;5:eaax1946. doi: https:\/\/doi.org\/10.1126\/sciadv.aax1946.","DOI":"10.1126\/sciadv.aax"},{"key":"503_CR20","first-page":"DC09-13","volume":"9","author":"AD Khosravi","year":"2015","unstructured":"Khosravi AD, Sadeghi P, Shahraki AH, Heidarieh P, Sheikhi N. Molecular methods for identification of acinetobacter species by partial sequencing of the rpoB and 16S rRNA genes. J Clin Diagn Res. 2015;9: DC09-13.","journal-title":"J Clin Diagn Res"},{"key":"503_CR21","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.burns.2014.08.018","volume":"41","author":"EA Montazeri","year":"2015","unstructured":"Montazeri EA, Khosravi AD, Jolodar A, Ghaderpanah M, Azarpira S. Identification of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from burn patients by multiplex PCR. Burns. 2015;41:590\u20134.","journal-title":"Burns"},{"key":"503_CR22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.30699\/ijp.2020.111181.2188","volume":"15","author":"K Jalalvand","year":"2020","unstructured":"Jalalvand K, Shayanfar N, Shahcheraghi F, Amini E, Mohammadpour M, Babaheidarian P. Evaluation of phenotypic and genotypic characteristics of carbapnemases-producing enterobacteriaceae and its prevalence in a referral hospital in Tehran city. Iran J Pathol. 2020;15:86\u201395.","journal-title":"Iran J Pathol"},{"key":"503_CR23","doi-asserted-by":"publisher","unstructured":"Weinstein MP, Lewis JS, 2nd. The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: Background, Organization, Functions, and Processes. J Clin Microbiol. 2020;58:e01864-19. doi:https:\/\/doi.org\/10.1128\/JCM.01864-19.","DOI":"10.1128\/JCM.01864-19"},{"key":"503_CR24","doi-asserted-by":"publisher","unstructured":"Harris G, KuoLee R, Xu HH, Chen W. Mouse models of Acinetobacter baumannii infection. Curr Protoc Microbiol. 2017;46:6G. 3.1-6G. 3.23. doi: https:\/\/doi.org\/10.1002\/cpmc.36.","DOI":"10.1002\/cpmc.36"},{"key":"503_CR25","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1128\/AAC.01944-13","volume":"58","author":"MG Thompson","year":"2014","unstructured":"Thompson MG, Black CC, Pavlicek RL, Honnold CL, Wise MC, Alamneh YA et al. Validation of a novel murine wound model of Acinetobacter baumannii infection. Antimicrob Agents Chemother. 2014;58:1332\u201342.","journal-title":"Antimicrob Agents Chemother"},{"key":"503_CR26","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jim.2014.04.007","volume":"410","author":"HK Kim","year":"2014","unstructured":"Kim HK, Missiakas D, Schneewind O. Mouse models for infectious diseases caused by Staphylococcus aureus. J Immunol Methods. 2014;410:88\u201399.","journal-title":"J Immunol Methods"},{"key":"503_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-017-02123-w","volume":"9","author":"MA Blaskovich","year":"2018","unstructured":"Blaskovich MA, Hansford KA, Gong Y, Butler MS, Muldoon C, Huang JX et al. Protein-inspired antibiotics active against vancomycin-and daptomycinresistant bacteria. Nat commun. 2018;9:1\u201317.","journal-title":"Nat commun."},{"key":"503_CR28","doi-asserted-by":"publisher","first-page":"5144","DOI":"10.1128\/AAC.01052-13","volume":"57","author":"L Tzouvelekis","year":"2013","unstructured":"Tzouvelekis L, Miriagou V, Kotsakis S, Spyridopoulou K, Athanasiou E, Karagouni E et al. KPC-producing, multidrug-resistant Klebsiella pneumoniae sequence type 258 as a typical opportunistic pathogen. Antimicrob Agents Chemother. 2013;57:5144\u20136.","journal-title":"Antimicrob Agents Chemother"},{"key":"503_CR29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41698-020-00129-0","volume":"4","author":"C Duffy","year":"2020","unstructured":"Duffy C, Sorolla A, Wang E, Golden E, Woodward E, Davern K et al. Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer. NPJ precis oncol. 2020;4:24.","journal-title":"NPJ precis oncol"},{"key":"503_CR30","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/j.bcp.2006.01.012","volume":"71","author":"S Maher","year":"2006","unstructured":"Maher S, McClean S. Investigation of the cytotoxicity of eukaryotic and prokaryotic antimicrobial peptides in intestinal epithelial cells in vitro. Biochem Pharmacol. 2006;71:1289\u201398.","journal-title":"Biochem Pharmacol"},{"key":"503_CR31","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s10989-017-9641-1","volume":"24","author":"H Zarrinnahad","year":"2018","unstructured":"Zarrinnahad H, Mahmoodzadeh A, Hamidi MP, Mahdavi M, Moradi A, Bagheri KP et al. Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line. Int J Pept Res Ther. 2018;24:563\u201370.","journal-title":"Int J Pept Res Ther"},{"key":"503_CR32","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12090582","author":"B Cheng","year":"2020","unstructured":"Cheng B, Xu P. Redox-Sensitive Nanocomplex for Targeted Delivery of Melittin. Toxins. 2020; doi:https:\/\/doi.org\/10.3390\/toxins12090582.","journal-title":"Toxins"},{"key":"503_CR33","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1080\/03639045.2018.1427760","volume":"44","author":"SH Rajabnejad","year":"2018","unstructured":"Rajabnejad SH, Mokhtarzadeh A, Abnous K, Taghdisi SM, Ramezani M, Razavi BM. Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer. Drug Dev Ind Pharm. 2018;44:982\u20137.","journal-title":"Drug Dev Ind Pharm"},{"key":"503_CR34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.exppara.2017.02.012","volume":"175","author":"C Carvalho","year":"2017","unstructured":"Carvalho C, Sobrinho-Junior E, Brito L, Nicolau L, Carvalho T, Moura A et al. Anti-Leishmania activity of essential oil of Myracrodruon urundeuva (Engl.) Fr. All.: Composition, cytotoxity and possible mechanisms of action. Exp Parasitol. 2017;175:59\u201367.","journal-title":"Exp Parasitol"},{"key":"503_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-56847-4","volume":"10","author":"I Greco","year":"2020","unstructured":"Greco I, Molchanova N, Holmedal E, Jenssen H, Hummel BD, Watts JL et al. Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides. Sci Rep. 2020;10:1\u201313.","journal-title":"Sci Rep"},{"key":"503_CR36","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jgar.2019.09.013","volume":"20","author":"Y Wang","year":"2020","unstructured":"Wang Y, Li H, Xie X, Wu X, Li X, Zhao Z et al. In vitro and in vivo assessment of the antibacterial activity of colistin alone and in combination with other antibiotics against Acinetobacter baumannii and Escherichia coli. Gol Antimicrob Resist. 2020;20:351\u20139.","journal-title":"Gol Antimicrob Resist"},{"key":"503_CR37","doi-asserted-by":"publisher","first-page":"4437","DOI":"10.1021\/mp500584u","volume":"11","author":"EL Ferguson","year":"2014","unstructured":"Ferguson EL, Azzopardi E, Roberts JL, Walsh TR, Thomas DW. Dextrin-colistin conjugates as a model bioresponsive treatment for multidrug resistant bacterial infections. Mol Pharm. 2014;11:4437\u201347.","journal-title":"Mol Pharm"},{"key":"503_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12070451","author":"H El-Seedi","year":"2020","unstructured":"El-Seedi H, El-Wahed A, Yosri N, Musharraf SG, Chen L, Moustafa M et al. Antimicrobial Properties of Apis mellifera\u2019s Bee Venom. Toxins (Basel). 2020; doi: https:\/\/doi.org\/10.3390\/toxins12070451.","journal-title":"Toxins (Basel)"},{"key":"503_CR39","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.etap.2013.06.009","volume":"36","author":"G Gajski","year":"2013","unstructured":"Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol. 2013;36:697\u2013705.","journal-title":"Environ Toxicol Pharmacol"},{"key":"503_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00997294","volume":"270","author":"E Habermann","year":"1971","unstructured":"Habermann E, Zeuner G. Comparative studies of native and synthetic melittins. Naunyn Schmiedebergs Arch Pharmakol. 1971;270:1\u20139.","journal-title":"Naunyn Schmiedebergs Arch Pharmakol"},{"key":"503_CR41","first-page":"111","volume":"3","author":"W Saeed","year":"2017","unstructured":"Saeed W, Khalil E. Toxic effects and safety of bee venom protein [Melittin] in mice: Search for natural vaccine adjuvants. IJNPR. 2017;3:111\u20134.","journal-title":"IJNPR"},{"key":"503_CR42","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/ame2.12099","volume":"3","author":"PGdS Pessini","year":"2020","unstructured":"Pessini PGdS, Knox de Souza PR, Chagas CdS, Sampaio EG, Neves DS, Petri G et al. Hematological reference values and animal welfare parameters of BALB\/C-FMABC (Mus musculus) inoculated with Ehrlich tumor kept in the vivarium at ABC Medical School. Animal Model Exp Med. 2020;3:32\u20139.","journal-title":"Animal Model Exp Med"},{"key":"503_CR43","doi-asserted-by":"publisher","first-page":"119071","DOI":"10.1016\/j.ijpharm.2020.119071","volume":"577","author":"Z Gui","year":"2020","unstructured":"Gui Z, Zhu J, Ye S, Ye J, Chen J, Ling Y et al. Prolonged melittin release from polyelectrolyte-based nanocomplexes decreases acute toxicity and improves blood glycemic control in a mouse model of type II diabetes. Int J Pharm. 2020;577:119071.","journal-title":"Int J Pharm"},{"key":"503_CR44","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/j.1469-0691.2011.03581.x","volume":"18","author":"X Vila-Farres","year":"2012","unstructured":"Vila-Farres X, De La Maria CG, L\u00f3pez-Rojas R, Pach\u00f3n J, Giralt E, Vila J. In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii. Clin Microbiol Infect. 2012;18:383\u20137.","journal-title":"Clin Microbiol Infect"},{"key":"503_CR45","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1016\/j.peptides.2003.08.003","volume":"24","author":"A Giacometti","year":"2003","unstructured":"Giacometti A, Cirioni O, Kamysz W, D\u2019Amato G, Silvestri C, Del Prete MS et al. Comparative activities of cecropin A, melittin, and cecropin A\u2013melittin peptide CA (1\u20137) M (2\u20139) NH2 against multidrug-resistant nosocomial isolates of Acinetobacter baumannii. Peptides. 2003;24:1315\u20138.","journal-title":"Peptides"},{"key":"503_CR46","doi-asserted-by":"publisher","first-page":"104011","DOI":"10.1016\/j.micpath.2020.104011","volume":"141","author":"AFM Pereira","year":"2020","unstructured":"Pereira AFM, Albano M, Alves FCB, Andrade BFMT, Furlanetto A, Rall VLM et al. Influence of apitoxin and melittin from Apis mellifera bee on Staphylococcus aureus strains. Microb Pathog. 2020;141:104011.","journal-title":"Microb Pathog"},{"key":"503_CR47","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1179\/1973947815Y.0000000004","volume":"28","author":"S Dosler","year":"2016","unstructured":"Dosler S, Karaaslan E, Alev Gerceker A. Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria. J chemother. 2016;28:95\u2013103.","journal-title":"J chemother"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-021-00503-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-021-00503-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-021-00503-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T21:04:45Z","timestamp":1699218285000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-021-00503-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["503"],"URL":"https:\/\/doi.org\/10.1186\/s40360-021-00503-z","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"assertion":[{"value":"28 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All study protocols human and animal studies were approved by the Mashhad University of Medical Sciences Ethics Committee (permit code: IR.MUMS.MEDICAL.REC.1399.151). Written informed consents were obtained from all healthy volunteer blood donors. Guidelines as drawn up by the institutional review board were followed. The guidelines meet the requirements of the Declaration of Helsinki or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare that they have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"42"}}