La ozonoterapia como adyuvante para el tratamiento del cáncer

26 Ene La ozonoterapia como adyuvante para el tratamiento del cáncer

Compartimos un artículo publicado en la prestigiosa editorial de Publimed / NIH National Library of Medicine ( National Center for Biotechnology Informatión), que explica las causas del porque la ozonoterapia sistémica es muy recomendable para proteger del daño de la Radioterapia y la Quimioterapia SIN INTERFERIR PARA NADA en el progreso de la enfermedad o eficacia de los tratamientos convencionales. Por eso entendemos que HAY QUE IMPLEMENTAR QUE SE REALICEN ENSAYOS CLINICOS.

Artículo original:

Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

https://pubmed.ncbi.nlm.nih.gov/30271455/

Traducción:

La ozonoterapia como adyuvante para el tratamiento del cáncer: ¿se justifica más investigación?
Bernardino Clavo 1 2 3 4 5, Norberto Santana-Rodríguez 4 6, Pedro Llontop 7, Dominga Gutiérrez 8, Gerardo Suárez 2, Laura López 2, Gloria Rovira 9, Gregorio Martínez-Sánchez 10, Esteban González 11, Ignacio J Jorge 3, Carmen Perera 12, Jesús Blanco 2, Francisco Rodríguez-Esparragón 1

Resumen
Introducción: este artículo proporciona una descripción general del uso potencial del ozono como adyuvante durante el tratamiento del cáncer.

Métodos: Resumimos los hallazgos de las publicaciones más relevantes enfocadas en este objetivo e incluimos nuestra experiencia clínica relacionada.

Resultados: A lo largo de varias décadas, revistas de prestigio han publicado estudios in vitro sobre la capacidad del ozono para inducir daño directo sobre las células tumorales y, además, potenciar los efectos de la radioterapia y la quimioterapia. Se han demostrado efectos indirectos en modelos animales: modulación inmune por ozono solo y efecto sensibilizador de la radioterapia por administración concurrente de ozono. Los efectos del ozono en la modificación de la curva de disociación de la hemoglobina, los niveles de 2,3-difosfoglicerato, el flujo sanguíneo locorregional y la hipoxia tumoral brindan apoyo adicional para los posibles efectos beneficiosos durante el tratamiento del cáncer. Desafortunadamente, solo se encuentran disponibles unos pocos estudios clínicos. Finalmente, describimos algunos trabajos y nuestra experiencia apoyando el papel potencial de la ozonoterapia local en el tratamiento del retraso en la cicatrización tras la resección del tumor, para evitar retrasos en el inicio de la radioterapia y la quimioterapia.

Conclusiones: Los estudios in vitro y en animales, así como los informes clínicos aislados, sugieren el papel potencial del ozono como adyuvante durante la radioterapia y / o quimioterapia. Sin embargo, se requiere más investigación, como ensayos clínicos aleatorios, para demostrar su utilidad potencial como herramienta terapéutica adyuvante.

FIGURA 1

Ozonoterapia y flujo sanguíneo cerebral evaluados por SPECT-ECD. Flujo sanguíneo cerebral evaluado mediante tomografía computarizada por emisión de fotón único (SPECT) con ECD (dímero de cisteinato de etilo 99mTc); el marcador se correlaciona con el flujo sanguíneo cerebral. La figura muestra a un paciente de 68 años con un glioblastoma parietooccipital izquierdo (astrocitoma grado IV) después de una resección subtotal. La SPECT con ECD se realizó antes (izquierda) y después de 3 sesiones de O3T en días alternos (derecha). Después de 3 sesiones de O3T, (1) el índice SPECT general en el cerebro aumentó del 60% al 90% y (2) en el área del tumor (sección # 11) el índice SPECT aumentó del 28% al 49%, aumento> 50% . Tenga en cuenta que hay diferentes escalas antes y después de O3T.

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    REFERENCIAS

  • 1. Bocci V., Borrelli E., Travagli V., Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Medicinal Research Reviews. 2009;29(4):646–682. doi: 10.1002/med.20150. – DOI – PubMed
  • 1. Bocci V. A., Zanardi I., Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. Journal of Translational Medicine. 2011;9, article 66 doi: 10.1186/1479-5876-9-66. – DOI – PMC – PubMed
  • 1. Brinkman R., Lamberts H. B. Ozone as a possible radiomimetic gas [13] Nature. 1958;181(4617):1202–1203. doi: 10.1038/1811202a0. – DOI – PubMed
  • 1. Schwartz-Tapia A., Martínez-Sánchez G., Sabah F. Madrid Declaration on Ozone Therapy., Madrid. Vol. 50. Madrid: ISCO3 (International Scientific Committee of Ozone Therapy); 2015. Madrid Declaration on Ozone Therapy 2015-2020 Eng.
  • 1. Baeza J., Cabo J. R., Gómez M., et al. WFOTs Review on Evidence Based Ozone Therapy. World Federation of Ozone Therapy. 2015:1–116.
  • 1. Fetner R. H. Chromosome breakage in Vicia faba by ozone [42] Nature. 1958;181(4607):504–505. doi: 10.1038/181504a0. – DOI
  • 1. Fetner R. H. Ozone-induced chromosome breakage in human cell cultures. Nature. 1962;194(4830):793–794. doi: 10.1038/194793a0. – DOI – PubMed
  • 1. Sweet F., Kao M.-S., Lee S.-C. D., Hagar W. L., Sweet W. E. Ozone selectively inhibits growth of human cancer cells. Science. 1980;209(4459):931–933. doi: 10.1126/science.7403859. – DOI – PubMed
  • 1. Karlic H., Kucera H., Metka M. Effect of ozone and ionizing radiation on an in vitro model–a pilot study of 4 gynecologic tumors. Strahlenther Onkol. 1987;163:37–42. – PubMed
  • 1. Zanker K. S., Kroczek R. In vitro synergistic activity of 5-fluorouracil with low-dose ozone against a chemoresistant tumor cell line and fresh human tumor cells. Chemotherapy. 1990;36(2):147–154. doi: 10.1159/000238761. – DOI – PubMed
  • 1. Cannizzaro A., Verga Falzacappa C., Martinelli M., Misiti S., Brunetti E., Bucci B. O2/3 exposure inhibits cell progression affecting cyclin B1/cdk1 activity in SK-N-SH while induces apoptosis in SK-N-DZ neuroblastoma cells. Journal of Cellular Physiology. 2007;213(1):115–125. doi: 10.1002/jcp.21097. – DOI – PubMed
  • 1. Simonetti V., Quagliariello V., Giustetto P., Franzini M., Iaffaioli R. V. Association of Ozone with 5-Fluorouracil and Cisplatin in Regulation of Human Colon Cancer Cell Viability: In Vitro Anti-Inflammatory Properties of Ozone in Colon Cancer Cells Exposed to Lipopolysaccharides. Evidence-Based Complementary and Alternative Medicine. 2017;2017:6. doi: 10.1155/2017/7414083.7414083 – DOI – PMC – PubMed
  • 1. Reuter S., Gupta S. C., Chaturvedi M. M., Aggarwal B. B. Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biology & Medicine. 2010;49(11):1603–1616. doi: 10.1016/j.freeradbiomed.2010.09.006. – DOI – PMC – PubMed
  • 1. Re L., Malcangi G., Martínez-Sánchez G. Medical ozone is now ready for a scientific challenge: current status and future perspectives. Journal of Experimental and Integrative Medicine. 2012;2:193–196. doi: 10.5455/jeim.070612.ir.012. – DOI
  • 1. Pryor W. A. How far does ozone penetrate into the pulmonary air/tissue boundary before it reacts? Free Radical Biology & Medicine. 1992;12(1):83–88. doi: 10.1016/0891-5849(92)90060-T. – DOI – PubMed
  • 1. Pryor W. A., Squadrito G. L., Friedman M. The cascade mechanism to explain ozone toxicity: The role of lipid ozonation products. Free Radical Biology & Medicine. 1995;19(6):935–941. doi: 10.1016/0891-5849(95)02033-7. – DOI – PubMed
  • 1. Re L., Martínez-Sánchez G., Bordicchia M., et al. Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result. European Journal of Pharmacology. 2014;742:158–162. doi: 10.1016/j.ejphar.2014.08.029. – DOI – PubMed
  • 1. Bocci V., Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Frontiers in Chemistry. 2015;3 – PMC – PubMed
  • 1. Pecorelli A., Bocci V., Acquaviva A., et al. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells. Toxicology and Applied Pharmacology. 2013;267(1):30–40. doi: 10.1016/j.taap.2012.12.001. – DOI – PubMed
  • 1. Rovira G., Clavo B., Perez J. L. Ozonoterapia tópica en el tratamiento de los retardos de cicatrización en pacientes oncológicos. Revista de Oncología. 1999;1:45–46.
  • 1. Menéndez S., Cepero J., Borrego L. Ozone therapy in cancer treatment: State of the art. Ozone: Sciende and Engineering. 2008;30(6):398–404. doi: 10.1080/01919510802473724. – DOI
  • 1. Schulz S., Häussler U., Mandic R., et al. Treatment with ozone/oxygen-pneumoperitoneum results in complete remission of rabbit squamous cell carcinomas. International Journal of Cancer. 2008;122(10):2360–2367. doi: 10.1002/ijc.23382. – DOI – PubMed
  • 1. Schulz S., Ninke S., Watzer B., Nüsing R. M. Ozone induces synthesis of systemic prostacyclin by cyclooxygenase-2 dependent mechanism in vivo. Biochemical Pharmacology. 2012;83(4):506–513. doi: 10.1016/j.bcp.2011.11.025. – DOI – PubMed
  • 1. Honn K. V., Cicone B., Skoff A. Prostacyclin: A potent antimetastatic agent. Science. 1981;212(4500):1270–1272. doi: 10.1126/science.7015512. – DOI – PubMed
  • 1. Rossmann A., Mandic R., Heinis J., et al. Intraperitoneal oxidative stress in rabbits with papillomavirus-associated head and neck cancer induces tumoricidal immune response that is adoptively transferable. Clinical Cancer Research. 2014;20(16):4289–4301. doi: 10.1158/1078-0432.CCR-14-0677. – DOI – PubMed
  • 1. Bocci V. Ozonetherapy as a possible biological response modifier in cancer. Forsch Komplementarmed. 1998;5:54–60. – PubMed
  • 1. Wang X., Bao Z., Zhang X., et al. Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: A systematic review and meta-analysis. Oncotarget . 2017;8(35):59901–59914. – PMC – PubMed
  • 1. Ohtsuka H., Ogata A., Terasaki N., Koiwa M., Kawamura S. Changes in leukocyte population after ozonated autohemoadministration in cows with inflammatory diseases. Journal of Veterinary Medical Science. 2006;68(2):175–178. doi: 10.1292/jvms.68.175. – DOI – PubMed
  • 1. Bocci V. A reasonable approach for the treatment of HIV infection in the early phase with ozonetherapy (autohaemotherapy). How ‘inflammatory’ cytokines may have a therapeutic role. Mediators Inflamm. 1994;3:315–321. – PMC – PubMed
  • 1. Bocci V. Ozone A new medical drug. Dordrecht, The Netherlands: Springer; 2005. Autoimmune diseases. Can ozone-therapy do better than antibodies to TNF alpha? pp. 149–162.
  • 1. Kuroda K., Azuma K., Mori T., et al. The safety and anti-tumor effects of ozonated water in vivo. International Journal of Molecular Sciences. 2015;16(10):25108–25120. doi: 10.3390/ijms161025108. – DOI – PMC – PubMed
  • 1. Hernuss P., Mueller Tyl E., Seitz W. The radiosensitizing effect of ozone in the animal experiment. Strahlentherapie und Onkologie. 1974;147(1):91–96. – PubMed
  • 1. Grundner H. G., Bauer E., Tramer G., Utesch E. Animal experimental examinations concerning the application of ozone to non irradiated and to irradiated tumors. I. Intravenous ozone therapy of Crocker sarcoma 180 and of Ehrlich’s carcinoma in the white mouse (German) Strahlentherapie und Onkologie. 1976;151(4):372–381. – PubMed
  • 1. Grundner H. G., Erler U. Experimentation on animals for investigation of ozone treatment in tumors with and without irradiation. II. Ehrlich ascites carcinoma in vivo. Strahlentherapie und Onkologie. 1976;151(6):522–529. – PubMed
  • 1. Grundner H. G. Animal experimental examinations concerning the application of ozone to non irradiated and to irradiated tumours. III. Ehrlich ascites cancer cells in vitro. Strahlentherapie und Onkologie. 1976;151(5):480–486. – PubMed
  • 1. Kiziltan H. S., Bayir A. G., Yucesan G. Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Altern Ther Health Med. 2015;21:24–29. – PubMed
  • 1. Dogan R., Hafız A. M., Kiziltan H. S., et al. Effectiveness of radiotherapy + ozone on tumoral tissue and survival in tongue cancer rat model. Auris Nasus Larynx. 2018;45(1):170–174. doi: 10.1016/j.anl.2016.12.010. – DOI – PubMed
  • 1. Vaupel P., Höckel M., Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxidants & Redox Signaling. 2007;9(8):1221–1235. doi: 10.1089/ars.2007.1628. – DOI – PubMed
  • 1. Gray L. H., Conger A. D., Ebert M., Hornsey S., Scott O. C. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. British Journal of Radiology. 1953;26(312):638–648. doi: 10.1259/0007-1285-26-312-638. – DOI – PubMed
  • 1. Horsman M. R., Vaupel P. Pathophysiological Basis for the Formation of the Tumor Microenvironment. Frontiers in Oncology. 2016;6 doi: 10.3389/fonc.2016.00066. – DOI – PMC – PubMed
  • 1. Nordsmark M., Bentzen S. M., Rudat V., et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiotherapy & Oncology. 2005;77(1):18–24. doi: 10.1016/j.radonc.2005.06.038. – DOI – PubMed
  • 1. Clavo B., Robaina F., Fiuza D., et al. Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification. Clinical and Translational Oncology. 2017;19(4):419–424. doi: 10.1007/s12094-016-1541-x. – DOI – PubMed
  • 1. Brizel D. M., Scully S. P., Harrelson J. M., et al. Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Research. 1996;56(5):941–943. – PubMed
  • 1. Clavo B., Pérez J. L., López L., Suárez G., et Ozone Therapy for Tumor Oxygenation: a Pilot Study. Evidence-Based Complementary and Alternative Medicine. 2004;1:93–98. doi: 10.1093/ecam/neh009.437019 – DOI – PMC – PubMed
  • 1. Falk S. J., Ward R., Bleehen N. M. The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. British Journal of Cancer. 1992;66(5):919–924. doi: 10.1038/bjc.1992.386. – DOI – PMC – PubMed
  • 1. Robaina F., Clavo B. The role of spinal cord stimulation in the management of patients with brain tumors. Acta Neurochirurgica, Supplementum. 2007;(97):445–453. doi: 10.1007/978-3-211-33079-1-58. – DOI – PubMed
  • 1. Mattassi R., D’Angelo F., Bisetti P. Terapia con ozono per via parenterale nelle arteriopatie obliteranti periferiche: mecanismo biochimico e risultati clinici. Il Giornale Di Chirurgia. 1987;VIII:109–111.
  • 1. Verrazzo G., Coppola L., Luongo C., et al. Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusive arterial disease. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc. 1995;22(1):17–22. – PubMed
  • 1. Giunta R., Coppola A., Luongo C., et al. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Annals of Hematology. 2001;80(12):745–748. doi: 10.1007/s002770100377. – DOI – PubMed
  • 1. Valacchi G., Bocci V. Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells. Mediators of Inflammation. 2000;9:271–276. doi: 10.1080/09629350020027573.649737 – DOI – PMC – PubMed
  • 1. Clavo B., Catalá L., Pérez J. L., Rodríguez V., Robaina F. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report. Evidence-Based Complementary and Alternative Medicine. 2004;1:5. doi: 10.1093/ecam/neh039.428436 – DOI – PMC – PubMed
  • 1. Robaina F., Clavo B. Spinal cord stimulation in the treatment of post-stroke patients: Current state and future directions. Acta Neurochirurgica, Supplementum. 2007;(97):277–282. doi: 10.1007/978-3-211-33079-1-37. – DOI – PubMed
  • 1. Clavo B., Perez J. L., Lopez L., et al. Effect of ozone therapy on muscle oxygenation. The Journal of Alternative and Complementary Medicine. 2003;9(2):251–256. doi: 10.1089/10755530360623365. – DOI – PubMed
  • 1. Bocci V., Larini A., Micheli V. Restoration of normoxia by ozone therapy may control neoplastic growth: A review and a working hypothtesis. The Journal of Alternative and Complementary Medicine. 2005;11(2):257–265. doi: 10.1089/acm.2005.11.257. – DOI – PubMed
  • 1. Luongo M., Brigida A. L., Mascolo L., Gaudino G. Possible therapeutic effects of ozone mixture on hypoxia in tumor development. Anticancer Reseach. 2017;37(2):425–436. doi: 10.21873/anticanres.11334. – DOI – PubMed
  • 1. Güçlü A., Erken H. A., Erken G., et al. The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy. International Urology and Nephrology. 2016;48(3):441–450. doi: 10.1007/s11255-015-1169-8. – DOI – PubMed
  • 1. Overgaard J. Hypoxic radiosensitization: Adored and ignored. Journal of Clinical Oncology. 2007;25(26):4066–4074. doi: 10.1200/JCO.2007.12.7878. – DOI – PubMed
  • 1. Overgaard J. Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck—a systematic review and meta-analysis. Radiotherapy & Oncology. 2011;100(1):22–32. doi: 10.1016/j.radonc.2011.03.004. – DOI – PubMed
  • 1. Bergofsky E. H., Bertun P. Response of regional circulations to hyperoxia. Journal of Applied Physiology. 1966;21(2):567–572. doi: 10.1152/jappl.1966.21.2.567. – DOI – PubMed
  • 1. Bergø G. W., Tyssebotn I. Cardiovascular effects of hyperbaric oxygen with and without addition of carbon dioxide. European Journal of Applied Physiology. 1999;80(4):264–275. doi: 10.1007/s004210050592. – DOI – PubMed
  • 1. Hernuss P., Müller-Tyl E., Dimopoulos J. Ozone-oxygen injection in gynecological radiotherapy. Strahlentherapie und Onkologie. 1974;148(3):242–245. – PubMed
  • 1. Muller-Tyl E., Hernuss P., Salzer H. Phospholipids under combined ozone-oxygen administration. Osterr Z Onkol. 1975;2:94–97. – PubMed
  • 1. Muller-Tyl E., Salzer H., Reisinger L. Ozone-oxygen therapy for gynecologic carcinomas. The effect of parenteral-ozone oxygen mixture administration on free fatty acids and triglycerides in patients with gynecologic carcinomas. Fortschr Med. 1979;97:451–454. – PubMed
  • 1. Enzelsberger H., Metka M., Salzer H. Effect of a parenteral ozone-oxygen mixture on the concentration of immunoglobulins (IgA, IgG, IgM), of vitamin A and lysozyme activity in patients with cervical cancer. Geburtshilfe und Frauenheilkunde. 1987;47(12):343–345. – PubMed
  • 1. Clavo B., Ruiz A., Lloret M., et al. Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study. Evidence-Based Complementary and Alternative Medicine. 2004;;1:321–325. doi: 10.1093/bioinformatics/neh038. – DOI – PMC – PubMed
  • 1. Parkhisenko I. A., Bil’chenko S. V. The ozone therapy in patients with mechanical jaundice of tumorous genesis. Vestnik khirurgii imeni I. I. Grekova. 2003;162(5):85–87. – PubMed
  • 1. Borrelli E. Treatment of advanced non-small-cell lung cancer with oxygen ozone therapy and mistletoe: an integrative approach. European Journal of Integrative Medicine. 2012;4:p. 130. doi: 10.1016/j.eujim.2012.07.775. – DOI
  • 1. Velez-Aguilar M. Terapia adyuvante con ozono en paciente con cáncer de páncreas metastásico. Revista Espa±ola de Ozonoterapia. 2015;5:21–31.
  • 1. Bocci V., Zanardi I., Pérez Olmedo J. C., Travagli V. A technically feasible treatment for peritoneal carcinomatosis. International Journal of Ozone Therapy. 2012;11(2):85–89.
  • 1. Stoker G. The surgical uses of ozone. The Lancet. 1916;188(4860):p. 712. doi: 10.1016/S0140-6736(01)31717-8. – DOI
  • 1. Stoker G. The surgical uses of ozone. The Lancet. 1917;189(4891):p. 797. doi: 10.1016/S0140-6736(01)49000-3. – DOI
  • 1. Martínez-Sánchez G., Re L., Pérez-Davison G. Las aplicaciones médicas de los aceites ozonizados, actualización. Revista Española de Ozonoterapia. 2012;2:121–139.
  • 1. Sechi L. A., Lezcano I., Nunez N., et al. Antibacterial activity of ozonized sunflower oil (Oleozon) Journal of Applied Microbiology. 2001;90(2):279–284. doi: 10.1046/j.1365-2672.2001.01235.x. – DOI – PubMed
  • 1. Rovira G., Galindo N. La ozonoterapia en el tratamiento de las úlceras crónicas de las extremidades inferiores. Angiologia. 1991;2:47–50. – PubMed
  • 1. Martínez-Sánchez G., Al-Dalain S. M., Menéndez S., et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology. 2005;523(1–3):151–161. doi: 10.1016/j.ejphar.2005.08.020. – DOI – PubMed
  • 1. Wainstein J., Feldbrin Z., Boaz M., Harman-Boehm I. Efficacy of ozone-oxygen therapy for the treatment of diabetic foot ulcers. Diabetes Technology & Therapeutics. 2011;13(12):1255–1260. doi: 10.1089/dia.2011.0018. – DOI – PubMed
  • 1. Smith N., Wilson A., Gandhi J., Vatsia S., Khan S. Ozone therapy: An overview of pharmacodynamics, current research, and clinical utility. Medical Gas Research. 2017;7(3):212–219. doi: 10.4103/2045-9912.215752. – DOI – PMC – PubMed
  • 1. Valacchi G., Fortino V., Bocci V. The dual action of ozone on the skin. British Journal of Dermatology. 2005;153(6):1096–1100. doi: 10.1111/j.1365-2133.2005.06939.x. – DOI – PubMed
  • 1. Sánchez G. M., Re L., Perez-Davison G. Las aplicaciones médicas de los aceites ozonizados, actualización. Rev Esp Ozonoterapia. 2012;2:121–139.
  • 1. Valacchi G., Lim Y., Belmonte G., et al. Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice. Wound Repair and Regeneration. 2011;19(1):107–115. doi: 10.1111/j.1524-475x.2010.00649.x. – DOI – PubMed
  • 1. Leite Rodrigues K., Catellani Cardoso C., Caputo L. R., Tavares Carvalho J. C., Evangelista Fiorini J., Schneedorf J. M. Cicatrizing and antimicrobial properties of an ozonised oil from sunflower seeds. Inflammopharmacology. 2004;12(3):261–270. doi: 10.1163/1568560042342275. – DOI – PubMed
  • 1. Kim H. S., Noh S. U., Han Y. W., et al. Therapeutic effects of topical application of ozone on acute cutaneous wound healing. Journal of Korean Medical Science. 2009;24(3):368–374. doi: 10.3346/jkms.2009.24.3.368. – DOI – PMC – PubMed
  • 1. Krkl C., Yiğit M. V., Özercan İ. H., Aygen E., Gültürk B., Artaş G. The Effect of Ozonated Olive Oil on Neovascularizatıon in an Experimental Skin Flap Model. Advances in Skin & Wound Care. 2016;29(7):322–327. doi: 10.1097/01.ASW.0000484172.04260.46. – DOI – PubMed
  • 1. Xiao W., Tang H., Wu M., et al. Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway. Bioscience Reports. 2017;37(6) – PMC – PubMed
  • 1. Clavo B., SantanaRodriguez N. Are we ready for a medical ozone challenge? Journal of Experimental and Integrative Medicine. 2012;2(3):p. 189. doi: 10.5455/jeim.170612.ed.014. – DOI