title: Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers.
abstract: Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%, P < 0.05). The wound size reduction was significantly more in ozone group than in control group (P < 0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415).
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis*; D005260:Female; D016523:Foot Ulcer / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000494:pharmacology / Q000627:therapeutic use*; D010126:Ozone / Q000494:pharmacology / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D010126:Ozone; D010100:Oxygen
references.citation: Biogerontology. 2012 Dec;13(6):565-81
references.pmid: 23001537
references.citation: Eur J Pharmacol. 2012 Sep 15;691(1-3):156-62
references.pmid: 22796450
references.citation: J Cardiovasc Pharmacol. 2013 Feb;61(2):160-5
references.pmid: 23222311
references.citation: Wound Repair Regen. 2006 Sep-Oct;14(5):558-65
references.pmid: 17014667
references.citation: Diabetes Care. 2009 Jan;32(1):117-9
references.pmid: 18835949
references.citation: Diabetes Technol Ther. 2011 Dec;13(12):1255-60
references.pmid: 21751891
references.citation: Lancet. 2005 Nov 12;366(9498):1719-24
references.pmid: 16291066
references.citation: Pharmacol Res. 2001 Nov;44(5):391-6
references.pmid: 11712870
references.citation: Med Res Rev. 2009 Jul;29(4):646-82
references.pmid: 19260079
references.citation: Mediators Inflamm. 2007;2007:65873
references.pmid: 17497036
references.citation: Acta Biomater. 2013 Aug;9(8):7814-21
references.pmid: 23603001
references.citation: Diabet Med. 2002 Jun;19(6):440-7
references.pmid: 12060054
references.citation: Eur J Pharmacol. 2005 Oct 31;523(1-3):151-61
references.pmid: 16198334
references.citation: J Wound Care. 2008 Jan;17(1):30-2, 34-7
references.pmid: 18210954
references.citation: Am J Surg. 2004 May;187(5A):71S-74S
references.pmid: 15147995
references.citation: Eur Rev Med Pharmacol Sci. 2012 Nov;16(12):1741-7
references.pmid: 23161050
references.citation: JAMA Dermatol. 2013 Sep;149(9):1050-8
references.pmid: 23884238
references.citation: Recent Pat Antiinfect Drug Discov. 2009 Jun;4(2):130-42
references.pmid: 19519548