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Published in: Archives of Gynecology and Obstetrics 5/2012

01-11-2012 | General Gynecology

Medical ozone therapy decreases postoperative uterine adhesion formation in rats

Authors: Bulent Uysal, Suzi Demirbag, Yavuz Poyrazoglu, Tuncer Cayci, Narter Yesildaglar, Ahmet Guven, Ilhami Sürer, Ahmet Korkmaz

Published in: Archives of Gynecology and Obstetrics | Issue 5/2012

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Abstract

Purpose

Various studies have been performed to find out novel treatment strategies to prevent postoperative adhesion formation. Ozone therapy (OT) is shown to reduce inflammation in several pathological conditions. Therefore, we aimed to evaluate the efficacy of OT in a rat model of experimental uterine adhesion (EUA).

Methods

Thirty female Wistar rats (200–250 g) were divided into three groups: sham, EUA and EUA+OT. EUA and EUA+OT groups were subjected to the postoperative adhesion procedure by bipolar coagulation on the uterine horns and corresponding pelvic sidewall parietal peritoneum. EUA+OT group received 0.7 mg/kg daily single dose for 3 days of ozone/oxygen mixture intraperitoneally after adhesion induction. All animals were killed on the 7th day and uterine adhesions were scored. Uterine tissues and peritoneal washing fluid were harvested for all analyses.

Results

Uterine malondialdehyde levels in the EUA group were significantly higher compared to the other groups. However, in the EUA group, uterine superoxide dismutase and glutathione peroxidase activities were lower than in other groups. Peritoneal fluid TNF-α levels were found to be significantly different for all groups (p < 0.001). Macroscopic total adhesion score was significantly higher in the EUA group compared to the other groups (p < 0.001). But, total score in the EUA+OT group was lower than in the EUA group (p = 0.006).

Conclusions

Medical OT prevents postoperative uterine adhesions by modulating TNF-α levels and oxidative/antioxidative status in an experimental uterine adhesion model.
Literature
1.
go back to reference Binda MM, Molinas CR, Koninckx PR (2003) Reactive oxygen species and adhesion formation: clinical implications in adhesion prevention. Hum Reprod 18:2503–2507PubMedCrossRef Binda MM, Molinas CR, Koninckx PR (2003) Reactive oxygen species and adhesion formation: clinical implications in adhesion prevention. Hum Reprod 18:2503–2507PubMedCrossRef
2.
go back to reference Rajab TK, Ahmad UN, Kelly E (2010) Implications of late complications from adhesions for preoperative informed consent. J R Soc Med 103:317–321PubMedCrossRef Rajab TK, Ahmad UN, Kelly E (2010) Implications of late complications from adhesions for preoperative informed consent. J R Soc Med 103:317–321PubMedCrossRef
3.
go back to reference Kelekci S, Uygur D, Yilmaz B et al (2007) Comparison of human amniotic membrane and hyaluronate/carboxymethylcellulose membrane for prevention of adhesion formation in rats. Arch Gynecol Obstet 276:355–359PubMedCrossRef Kelekci S, Uygur D, Yilmaz B et al (2007) Comparison of human amniotic membrane and hyaluronate/carboxymethylcellulose membrane for prevention of adhesion formation in rats. Arch Gynecol Obstet 276:355–359PubMedCrossRef
4.
go back to reference Roy S, Clark CJ, Mohebali K et al (2004) Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesions. World J Surg 28:316–320PubMedCrossRef Roy S, Clark CJ, Mohebali K et al (2004) Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesions. World J Surg 28:316–320PubMedCrossRef
5.
go back to reference ten Raa S, van den Tol MP, Sluiter W et al (2006) The role of neutrophils and oxygen free radicals in post-operative adhesions. J Surg Res 136:45–52PubMedCrossRef ten Raa S, van den Tol MP, Sluiter W et al (2006) The role of neutrophils and oxygen free radicals in post-operative adhesions. J Surg Res 136:45–52PubMedCrossRef
6.
go back to reference Gotloib L, Wajsbrot V, Cuperman Y et al (2004) Acute oxidative stress induces peritoneal hyperpermeability, mesothelial loss, and fibrosis. J Lab Clin Med 143:31–40PubMedCrossRef Gotloib L, Wajsbrot V, Cuperman Y et al (2004) Acute oxidative stress induces peritoneal hyperpermeability, mesothelial loss, and fibrosis. J Lab Clin Med 143:31–40PubMedCrossRef
7.
go back to reference Kaidi AA, Nazzal M, Gurchumelidze T et al (1995) Preoperative administration of antibodies against tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. Am Surg 61:569–572PubMed Kaidi AA, Nazzal M, Gurchumelidze T et al (1995) Preoperative administration of antibodies against tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. Am Surg 61:569–572PubMed
8.
go back to reference Mirastschijski U, Johannesson K, Jeppsson B et al (2005) Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor on intra-abdominal adhesions. Eur Surg Res 37:68–75PubMedCrossRef Mirastschijski U, Johannesson K, Jeppsson B et al (2005) Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor on intra-abdominal adhesions. Eur Surg Res 37:68–75PubMedCrossRef
9.
go back to reference Saba AA, Godziachvili V, Mavani AK et al (1998) Serum levels of interleukin 1 and tumor necrosis factor alpha correlate with peritoneal adhesion grades in humans after major abdominal surgery. Am Surg 64:734–736 discussion 737PubMed Saba AA, Godziachvili V, Mavani AK et al (1998) Serum levels of interleukin 1 and tumor necrosis factor alpha correlate with peritoneal adhesion grades in humans after major abdominal surgery. Am Surg 64:734–736 discussion 737PubMed
10.
go back to reference Williams RS, Rossi AM, Chegini N et al (1992) Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum. J Surg Res 52:65–70PubMedCrossRef Williams RS, Rossi AM, Chegini N et al (1992) Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum. J Surg Res 52:65–70PubMedCrossRef
11.
go back to reference Cheong YC, Laird SM, Shelton JB et al (2002) The correlation of adhesions and peritoneal fluid cytokine concentrations: a pilot study. Hum Reprod 17:1039–1045PubMedCrossRef Cheong YC, Laird SM, Shelton JB et al (2002) The correlation of adhesions and peritoneal fluid cytokine concentrations: a pilot study. Hum Reprod 17:1039–1045PubMedCrossRef
12.
go back to reference Kurukahvecioglu O, Koksal H, Gulbahar O et al (2007) Infliximab “TNF-alpha antagonist” decreases intraabdominal adhesions. Saudi Med J 28:1830–1835PubMed Kurukahvecioglu O, Koksal H, Gulbahar O et al (2007) Infliximab “TNF-alpha antagonist” decreases intraabdominal adhesions. Saudi Med J 28:1830–1835PubMed
13.
go back to reference Bocci V (2004) Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm 13:3–11PubMedCrossRef Bocci V (2004) Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm 13:3–11PubMedCrossRef
14.
go back to reference Bocci VA (2006) Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 37:425–435PubMedCrossRef Bocci VA (2006) Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 37:425–435PubMedCrossRef
15.
go back to reference Oter S, Korkmaz A (2006) Relevance of hyperbaric oxygen to ozone therapy. Arch Med Res 37:917–918 author reply 919PubMedCrossRef Oter S, Korkmaz A (2006) Relevance of hyperbaric oxygen to ozone therapy. Arch Med Res 37:917–918 author reply 919PubMedCrossRef
16.
go back to reference Bocci V (1996) Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses 46:150–154PubMedCrossRef Bocci V (1996) Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses 46:150–154PubMedCrossRef
17.
go back to reference Guven A, Gundogdu G, Vurucu S et al (2009) Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 44:1730–1735PubMedCrossRef Guven A, Gundogdu G, Vurucu S et al (2009) Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 44:1730–1735PubMedCrossRef
18.
go back to reference Kesik V, Uysal B, Kurt B et al (2009) Ozone ameliorates methotrexate-induced intestinal injury in rats. Cancer Biol Ther 8:1623–1628PubMedCrossRef Kesik V, Uysal B, Kurt B et al (2009) Ozone ameliorates methotrexate-induced intestinal injury in rats. Cancer Biol Ther 8:1623–1628PubMedCrossRef
19.
go back to reference Uysal B, Yasar M, Ersoz N et al (2010) Efficacy of hyperbaric oxygen therapy and medical ozone therapy in experimental acute necrotizing pancreatitis. Pancreas 39:9–15PubMedCrossRef Uysal B, Yasar M, Ersoz N et al (2010) Efficacy of hyperbaric oxygen therapy and medical ozone therapy in experimental acute necrotizing pancreatitis. Pancreas 39:9–15PubMedCrossRef
20.
go back to reference Di Filippo C, Luongo M, Marfella R, Ferraraccio F, Lettieri B, Capuano A, Rossi F, D’Amico M (2010) Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment. Naunyn Schmiedebergs Arch Pharmacol 382:287–291PubMedCrossRef Di Filippo C, Luongo M, Marfella R, Ferraraccio F, Lettieri B, Capuano A, Rossi F, D’Amico M (2010) Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment. Naunyn Schmiedebergs Arch Pharmacol 382:287–291PubMedCrossRef
21.
go back to reference Chu DI, Lim R, Heydrick S et al (2011) N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses. Surgery 149:801–812PubMedCrossRef Chu DI, Lim R, Heydrick S et al (2011) N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses. Surgery 149:801–812PubMedCrossRef
22.
go back to reference Cetinkursun S, Demirbag S, Tasdemir U et al (2005) Comparison of hyaluronate/carboxymethylcellulose membrane and melatonin for prevention of adhesion formation in a rat model. Hum Reprod 20:2021–2024PubMedCrossRef Cetinkursun S, Demirbag S, Tasdemir U et al (2005) Comparison of hyaluronate/carboxymethylcellulose membrane and melatonin for prevention of adhesion formation in a rat model. Hum Reprod 20:2021–2024PubMedCrossRef
23.
go back to reference Basbug M, Aygen E, Tayyar M et al (1998) Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion formation in rat uterine horn model. Eur J Obstet Gynecol Reprod Biol 78:109–112PubMedCrossRef Basbug M, Aygen E, Tayyar M et al (1998) Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion formation in rat uterine horn model. Eur J Obstet Gynecol Reprod Biol 78:109–112PubMedCrossRef
24.
go back to reference Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMed Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMed
25.
go back to reference Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRef Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRef
26.
go back to reference Durak I, Yurtarslanl Z, Canbolat O et al (1993) A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 214:103–104PubMedCrossRef Durak I, Yurtarslanl Z, Canbolat O et al (1993) A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 214:103–104PubMedCrossRef
27.
go back to reference Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMed Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMed
28.
go back to reference Leach RE, Burns JW, Dawe EJ et al (1998) Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel. Fertil Steril 69:415–418PubMedCrossRef Leach RE, Burns JW, Dawe EJ et al (1998) Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel. Fertil Steril 69:415–418PubMedCrossRef
29.
go back to reference Di Filippo C, Capuano A, Rinaldi B et al (2011) Intraperitoneal oxygen/ozone treatment decreases the formation of experimental postsurgical peritoneal adhesions and the levels/activity of the local ubiquitin–proteasome system. Mediators Inflamm 2011:606718PubMed Di Filippo C, Capuano A, Rinaldi B et al (2011) Intraperitoneal oxygen/ozone treatment decreases the formation of experimental postsurgical peritoneal adhesions and the levels/activity of the local ubiquitin–proteasome system. Mediators Inflamm 2011:606718PubMed
30.
go back to reference Di Domenico I, Dimarzio G, Pepe L, Lettieri B (2011) Comparision between O2 and oxygen/ozone mixture treatment in decreasing postsurgical peritoneal adhesion and the levels/activity of local ubiquitine–proteasome system.Translational Medicine @ UniSa, Special Issues 1(4 Poster) Di Domenico I, Dimarzio G, Pepe L, Lettieri B (2011) Comparision between O2 and oxygen/ozone mixture treatment in decreasing postsurgical peritoneal adhesion and the levels/activity of local ubiquitine–proteasome system.Translational Medicine @ UniSa, Special Issues 1(4 Poster)
31.
go back to reference Yesildaglar N, Ordonez JL, Laermans I et al (1999) The mouse as a model to study adhesion formation following endoscopic surgery: a preliminary report. Hum Reprod 14:55–59PubMedCrossRef Yesildaglar N, Ordonez JL, Laermans I et al (1999) The mouse as a model to study adhesion formation following endoscopic surgery: a preliminary report. Hum Reprod 14:55–59PubMedCrossRef
32.
go back to reference Yesildaglar N, Koninckx PR (2000) Adhesion formation in intubated rabbits increases with high insufflation pressure during endoscopic surgery. Hum Reprod 15:687–691PubMedCrossRef Yesildaglar N, Koninckx PR (2000) Adhesion formation in intubated rabbits increases with high insufflation pressure during endoscopic surgery. Hum Reprod 15:687–691PubMedCrossRef
33.
go back to reference Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107:395–418PubMed Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107:395–418PubMed
34.
go back to reference Dijkgraaf LC, Zardeneta G, Cordewener FW et al (2003) Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial step in adhesion formation in osteoarthritis of the temporomandibular joint. J Oral Maxillofac Surg 61:101–111PubMedCrossRef Dijkgraaf LC, Zardeneta G, Cordewener FW et al (2003) Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial step in adhesion formation in osteoarthritis of the temporomandibular joint. J Oral Maxillofac Surg 61:101–111PubMedCrossRef
35.
go back to reference Bertuglia S, Colantuoni A, Intaglietta M (1993) Effect of leukocyte adhesion and microvascular permeability on capillary perfusion during ischemia–reperfusion injury in hamster cheek pouch. Int J Microcirc Clin Exp 13:13–26PubMed Bertuglia S, Colantuoni A, Intaglietta M (1993) Effect of leukocyte adhesion and microvascular permeability on capillary perfusion during ischemia–reperfusion injury in hamster cheek pouch. Int J Microcirc Clin Exp 13:13–26PubMed
36.
go back to reference Demirbag S, Uysal B, Guven A et al (2010) Effects of medical ozone therapy on acetaminophen-induced nephrotoxicity in rats. Ren Fail 32:493–497PubMedCrossRef Demirbag S, Uysal B, Guven A et al (2010) Effects of medical ozone therapy on acetaminophen-induced nephrotoxicity in rats. Ren Fail 32:493–497PubMedCrossRef
37.
go back to reference Bocci V, Zanardi I, Travagli V (2011) Has oxygen–ozone therapy a future in medicine? J Exp Integr Med 1:5–11CrossRef Bocci V, Zanardi I, Travagli V (2011) Has oxygen–ozone therapy a future in medicine? J Exp Integr Med 1:5–11CrossRef
38.
go back to reference Souza YM, Fontes B, Martins JO, Sannomiya P, Brito GS, Younes RN, Rasslan S (2010) Evaluation of the effects of ozone therapy in the treatment of intra-abdominal infection in rats. Clinics (Sao Paulo) 65:195–202CrossRef Souza YM, Fontes B, Martins JO, Sannomiya P, Brito GS, Younes RN, Rasslan S (2010) Evaluation of the effects of ozone therapy in the treatment of intra-abdominal infection in rats. Clinics (Sao Paulo) 65:195–202CrossRef
39.
go back to reference Rodríguez ZZ, Guanche D, Alvarez RG, Martinez Y, Alonso Y, Schulz S (2011) Effects of ozone oxidative preconditioning on different hepatic biomarkers of oxidative stress in endotoxic shock in mice. Toxicol Mech Methods 21:236–240PubMedCrossRef Rodríguez ZZ, Guanche D, Alvarez RG, Martinez Y, Alonso Y, Schulz S (2011) Effects of ozone oxidative preconditioning on different hepatic biomarkers of oxidative stress in endotoxic shock in mice. Toxicol Mech Methods 21:236–240PubMedCrossRef
40.
go back to reference Guven A, Gundogdu G, Sadir S et al (2008) The efficacy of ozone therapy in experimental caustic esophageal burn. J Pediatr Surg 43:1679–1684PubMedCrossRef Guven A, Gundogdu G, Sadir S et al (2008) The efficacy of ozone therapy in experimental caustic esophageal burn. J Pediatr Surg 43:1679–1684PubMedCrossRef
Metadata
Title
Medical ozone therapy decreases postoperative uterine adhesion formation in rats
Authors
Bulent Uysal
Suzi Demirbag
Yavuz Poyrazoglu
Tuncer Cayci
Narter Yesildaglar
Ahmet Guven
Ilhami Sürer
Ahmet Korkmaz
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 5/2012
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-012-2435-y

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