{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:11:48Z","timestamp":1790727108386,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bia\u0142ystok","doi-asserted-by":"publisher","award":["N\/ST\/ZB\/16\/002\/1152"],"award-info":[{"award-number":["N\/ST\/ZB\/16\/002\/1152"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Autohemotherapy with ozonated blood is used in the treatment of a broad spectrum of clinical disorders. Ozone demonstrates strong oxidizing properties and causes damage to cell membranes. The impact of whole-blood ozonation on the release of microparticles from blood and endothelial cells and the concentration of selected markers in the hemostatic system (APTT, PT, D-dimer, fibrinogen) were investigated. Venous blood, obtained from 19 healthy men, was split into four equal parts and treated with air, 15 \u00b5g\/mL ozone, or 30 \u00b5g\/mL ozone, or left untreated. The number and types of microparticles released were determined using flow cytometry on the basis of surface antigen expression: erythrocyte-derived microparticles (CD235+), platelet-derived microparticles (CD42+), leukocyte-derived microparticles (CD45+), and endothelial-derived microparticles (CD144+). The study is the first to demonstrate that ozone induces a statistically significant increase in the number of microparticles derived from blood and endothelial cells. Although statistically significant, the changes in some coagulation factors were somewhat mild and did not exceed normal values.<\/jats:p>","DOI":"10.3390\/biom12020164","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T08:37:18Z","timestamp":1642754238000},"page":"164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ozonation of Whole Blood Results in an Increased Release of Microparticles from Blood Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Barbara","family":"Boczkowska-Radziwon","sequence":"first","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr J\u00f3zef","family":"Olbromski","sequence":"additional","affiliation":[{"name":"Department of Gynecology IV, Gynecology-Obstetrics University Hospital, 60-235 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rogowska","sequence":"additional","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Bujno","sequence":"additional","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-2589","authenticated-orcid":false,"given":"Marta","family":"My\u015bliwiec","sequence":"additional","affiliation":[{"name":"Department of Oncology, Medical University of Bialystok, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"\u017bebrowska","sequence":"additional","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"\u015aredzi\u0144ski","sequence":"additional","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Polity\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Psychology and Philosophy, Medical University of Bialystok, 15-950 Bialystok, Poland"},{"name":"Robinson College, University of Cambridge, Cambridge CB3 9AN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-8188","authenticated-orcid":false,"given":"Marek Z.","family":"Wojtukiewicz","sequence":"additional","affiliation":[{"name":"Department of Oncology, Medical University of Bialystok, 15-027 Bialystok, Poland"},{"name":"Department of Clinical Oncology, Comprehensive Cancer Center, 15-950 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Radziwon","sequence":"additional","affiliation":[{"name":"Regional Center for Transfusion Medicine, 15-950 Bialystok, Poland"},{"name":"Department of Hematology, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/1811202a0","article-title":"Ozone as a possible radiomimetic gas","volume":"181","author":"Brinkman","year":"1958","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4103\/2045-9912.215752","article-title":"Ozone therapy: An overview of pharmacodynamics, current research, and clinical utility","volume":"7","author":"Smith","year":"2017","journal-title":"Med. Gas Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/acm.2005.11.257","article-title":"Restoration of normoxia by ozone therapy may control neoplastic growth: A review and a working hypothesis","volume":"11","author":"Bocci","year":"2005","journal-title":"J. Altern. Complement. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s11845-011-0675-7","article-title":"The effects of ozone therapy and coenzyme Q(1)(0) combination on oxidative stress markers in healthy subjects","volume":"180","author":"Inal","year":"2011","journal-title":"Ir. J. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1479-5876-9-66","article-title":"Ozone acting on human blood yields a hormetic dose-response relationship","volume":"9","author":"Bocci","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.2147\/JPR.S154154","article-title":"The effect and safety of ozone autohemotherapy combined with pharmacological therapy in postherpetic neuralgia","volume":"11","author":"Hu","year":"2018","journal-title":"J. Pain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1002\/jcp.26044","article-title":"Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain","volume":"233","author":"Braidy","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.2174\/187152909788488681","article-title":"May oxygen-ozone therapy improves cardiovascular disorders?","volume":"9","author":"Bocci","year":"2009","journal-title":"Cardiovasc. Hematol. Disord. Drug Targets"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/01919512.2016.1191992","article-title":"Ozone in medicine: Clinical evaluation and evidence classification of the systemic ozone applications, major autohemotherapy and rectal insufflation, according to the requirements for evidence-based medicine","volume":"38","author":"Fahmy","year":"2016","journal-title":"Ozone Sci. Eng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e9265","DOI":"10.1097\/MD.0000000000009265","article-title":"Ozone therapy induced sinus arrest in a hypertensive patient with chronic kidney disease. A case report","volume":"96","author":"Ang","year":"2017","journal-title":"Medicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000431078","article-title":"Myocardial infarction after ozone therapy: Is ozone therapy dr. Jekyll or Mr. Hyde?","volume":"132","author":"Arslan","year":"2015","journal-title":"Cardiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s002770100377","article-title":"Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease","volume":"80","author":"Giunta","year":"2001","journal-title":"Ann. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s10517-009-0340-6","article-title":"Modulation of phagocytic activity of blood polynuclear leukocytes with ozonized physiological saline","volume":"146","author":"Volkhovskaya","year":"2008","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_14","first-page":"510","article-title":"Studies on the biological effects of ozone 1. Induction of interferon gamma on human leucocytes","volume":"75","author":"Bocci","year":"1990","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0092-8674(86)90807-X","article-title":"Inducibility of kappa immunoglobulin enhance binding protein Nf-kappa B by a posttranslational mechanism","volume":"47","author":"Sen","year":"1986","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.iy.12.040194.001041","article-title":"Function and activation of NF-kappa B in the immune system","volume":"12","author":"Baeuerle","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104178","DOI":"10.1016\/j.cellimm.2020.104178","article-title":"A humoral solution: Autologous blood products and tissue repair","volume":"356","author":"Yogev","year":"2020","journal-title":"Cell. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1111\/j.1365-2672.2008.04141.x","article-title":"How much ozone bactericidal activity is compromised by plasma components?","volume":"106","author":"Burgassi","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/09629359990360","article-title":"Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets","volume":"8","author":"Valacchi","year":"1999","journal-title":"Mediat. Inflamm."},{"key":"ref_20","first-page":"860","article-title":"The effect of ozone therapy on experimental vasospasm in the rat femoral artery","volume":"26","author":"Orakdogen","year":"2016","journal-title":"Turk. Neurosurg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/039139880002300212","article-title":"Extracorporeal blood oxygenation and ozonation (EBOO) in man. preliminary report","volume":"23","author":"Bocci","year":"2000","journal-title":"Int. J. Artif. Organs."},{"key":"ref_22","first-page":"47","article-title":"Visual improvement following ozone therapy in dry age related macular degeneration; a review","volume":"2","author":"Borrelli","year":"2013","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejphar.2014.08.029","article-title":"Is ozone pre-conditioning effect linked to Nrf2\/EpRE activation pathway in vivo? A preliminary result","volume":"742","author":"Re","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cisterna, B., Costanzo, M., Nodari, A., Gali\u00e8, M., Zanzoni, S., Bernardi, P., Covi, V., Tabaracci, G., and Malatesta, M. (2020). Ozone activates the Nrf2 pathway and improves preservation of explanted adipose tissue in vitro. Antioxidants, 9.","DOI":"10.3390\/antiox9100989"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gali\u00e8, M., Covi, V., Tabaracci, G., and Malatesta, M. (2019). The role of Nrf2 in the antioxidant cellular response to medical ozone exposure. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164009"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.4330\/wjc.v6.i11.1135","article-title":"Role of microparticles in endothelial dysfunction and arterial hypertension","volume":"6","author":"Helbing","year":"2014","journal-title":"World J. Cadiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1111\/jth.13871","article-title":"Tissue factor-bearing microparticles and inflammation: A potential mechanism for the development of venous thromboembolism in cancer","volume":"15","author":"Date","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1161\/CIRCRESAHA.110.226456","article-title":"Microparticles: Protagonists of a novel communication network for intercellular information exchange","volume":"107","author":"Mause","year":"2010","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/1947601913499020","article-title":"Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: A mechanism of intercellular signaling in human hepatocellular cancer","volume":"4","author":"Kogure","year":"2013","journal-title":"Genes Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1161\/ATVBAHA.112.300139","article-title":"Intercellular transport of microRNAs","volume":"33","author":"Boon","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1189\/jlb.0607373","article-title":"Inflammation, endothelium, and coagulation in sepsis","volume":"83","author":"Schouten","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1161\/CIRCRESAHA.110.233163","article-title":"Microparticles, vascular function, and atherothrombosis","volume":"109","author":"Rautou","year":"2011","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1111\/j.1538-7836.2012.04758.x","article-title":"Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa","volume":"10","author":"Van","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lipets, E., Vlasova, O., Urnova, E., Margolin, O., Soloveva, A., Ostapushchenko, O., Andersen, J., Ataullakhanov, F., and Panteleev, M. (2014). Circulating contact-pathway-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic Patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087692"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1055\/s-0036-1592301","article-title":"Microparticles and fibrinolysis","volume":"43","author":"Vallier","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s12253-020-00854-8","article-title":"Elevated microparticles, thrombin-antithrombin and VEGF levels in colorectal cancer patients undergoing chemotherapy","volume":"26","author":"Wojtukiewicz","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.1021\/pr3008946","article-title":"Combination of LC-MS- and GC-MS-based metabolomics to study the effect of ozonated autohemotherapy on human blood","volume":"11","author":"Ciborowski","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1177\/1091581809360069","article-title":"Effects of ozone blood treatment on the metabolite profile of human blood","volume":"29","author":"Travagli","year":"2010","journal-title":"Int. J. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.transci.2015.10.010","article-title":"An overview of the role of microparticles\/microvesicles in blood components: Are they clinically beneficial or harmful?","volume":"53","author":"Burnouf","year":"2015","journal-title":"Transfus. Apher. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.transci.2016.10.018","article-title":"Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing","volume":"255","author":"Almizraq","year":"2016","journal-title":"Transfus. Apher. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.thromres.2010.12.014","article-title":"Measurement of circulating cell-derived microparticles by flow cytometry: Sources of variability within the assay","volume":"127","author":"Ayersa","year":"2011","journal-title":"Thromb. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.transci.2018.07.018","article-title":"Effects of donor age, donor sex, blood-component processing, and storage on cell-derived microparticle concentrations in routine blood-component preparation","volume":"57","author":"Noulsri","year":"2018","journal-title":"Transfus. Apher. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.transci.2017.03.007","article-title":"Extracellular vesicle characteristics in stored red blood cell concentrates are influenced by the method of detection","volume":"56","author":"Almizraq","year":"2017","journal-title":"Transfus. Apher. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/vox.12014","article-title":"Elevated levels of thrombin-generating microparticles in stored red blood cells","volume":"105","author":"Gao","year":"2013","journal-title":"Vox Sang."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1159\/000342228","article-title":"Red blood cell microparticles: Clinical relevance","volume":"39","author":"Rubin","year":"2012","journal-title":"Transfus. Med. Hemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1365-2249.2010.04271.x","article-title":"Ectosomes as modulators of inflammation and immunity","volume":"163","author":"Sadallah","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.blre.2006.09.001","article-title":"Circulating microparticles: Pathophysiology and clinical implications","volume":"21","author":"Piccin","year":"2007","journal-title":"Blood Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.freeradbiomed.2014.08.018","article-title":"Ozone-induced oxidative modification of fibrinogen: Role of the D regions","volume":"77","author":"Rosenfeld","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1111\/trf.12008","article-title":"Red blood celliderived microparticles isolated from blood units initiate and propagate thrombin generation","volume":"53","author":"Olivier","year":"2013","journal-title":"Transfusion"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.3324\/haematol.2012.066167","article-title":"Leukocyte- and endothelial-derived microparticles: A circulating source for fibrinolysis","volume":"97","author":"Lacroix","year":"2012","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000443604","article-title":"Ozone therapy and its use in medicine","volume":"134","author":"Re","year":"2016","journal-title":"Cardiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.arcmed.2006.06.006","article-title":"Blood coagulation unaffected by ozonated autohemotherapy in patients on maintenance hemodialysis","volume":"37","author":"Biedunkiewicz","year":"2006","journal-title":"Arch. Med. Res."},{"key":"ref_53","first-page":"45","article-title":"Efecto del ozono sobre la actividad plaquetaria en paciente diab\u00e9ticos tratados con ozonoterapia: Informe preliminar","volume":"20","author":"Pina","year":"2001","journal-title":"Rev. Cuba. Investig. Biomed."},{"key":"ref_54","first-page":"41","article-title":"Effect of ozone oxidative preconditioning on bleeding time and venous thrombosis in a septic shock model in rats","volume":"41","author":"Zamora","year":"2010","journal-title":"Cienc. Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:05:04Z","timestamp":1760133904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["biom12020164"],"URL":"https:\/\/doi.org\/10.3390\/biom12020164","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,21]]}}}