Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2014 Volume 9 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2014 Volume 9 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury

  • Authors:
    • Nan Kang
    • Yong Hai
    • Fang Liang
    • Chun‑Jin Gao
    • Xue‑Hua Liu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China
    Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2124-2130
    |
    Published online on: March 24, 2014
       https://doi.org/10.3892/mmr.2014.2064
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Hyperbaric oxygen (HBO) therapy is an effective therapy for ischemia/reperfusion (I/R) injury of the brain, small intestine, testes and liver. However, the detailed molecular mechanisms underlying the effect of HBO therapy remain undetermined. In the current study, the hypothesis that preconditioning rats with HBO protects grafted skin flaps against subsequent I/R injury was investigated. In addition, the molecular mechanisms underlying HBO therapy were characterized by analyzing the roles of the following important inflammatory factors: High mobility group protein 1 (HMGB1) and nuclear factor‑κ B (NF‑κB). A total of 40 rats were randomly divided into the following five groups: (i) Sham surgery (SH); (ii) ischemia followed by reperfusion 3 days following surgery (I/R3d); (iii) ischemia followed by reperfusion 5 days following surgery (I/R5d); (iv) HBO preconditioning (HBO‑PC) and ischemia followed by reperfusion 3 days following surgery (HBO‑PC+3d); and (v) HBO‑PC and ischemia followed by reperfusion 5 days following surgery (HBO‑PC+5d). For the surgical procedure, all pedicled skin flaps were first measured and elevated (9x6 cm). The feeding vessels of the skin flaps were subsequently clamped for 3 h and released to restore blood flow. The rats in the HBO‑PC+3d and HBO‑PC+5d groups received 1 h HBO for 3 and 5 consecutive days, respectively, prior to surgery. Following surgery, the rats were euthanized, and grafted tissues were collected for western blotting and immunohistochemistry. HBO‑PC increased blood perfusion in epigastric skin flaps and attenuated I/R injury following skin flap graft. Additionally, the elevated expression of HMGB1 and NF‑κB proteins during I/R injury was attenuated by HBO‑PC treatment. HBO‑PC may therefore be applied to reduce I/R injury and improve the survival rate of grafted skin flaps. The molecular mechanisms underlying the effect of HBO therapy are associated with the attenuation of inflammatory responses.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kerrigan CL and Stotland MA: Ischemia reperfusion injury: a review. Microsurgery. 14:165–175. 1993. View Article : Google Scholar : PubMed/NCBI

2 

Siemionow M and Arslan E: Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery. 24:468–475. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Yoshida WB and Campos EB: Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model. Acta Cir Bras. 20:358–363. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Kuo YR, Wang FS, Jeng SF, Huang HC, Wei FC and Yang KD: Nitrosoglutathione modulation of platelet activation and nitric oxide synthase expression in promotion of flap survival after ischemia/reperfusion injury. J Surg Res. 119:92–99. 2004. View Article : Google Scholar

5 

Xiong LZ, Zhu ZH, Dong HL, Hu W, Hou L and Chen S: Hyperbaric oxygen preconditioning induces neuroprotection against transient not permanent middle cerebral artery occlusion rat model. Chin Med J (Engl). 113:836–839. 2000.

6 

Dong H, Xiong L, Zhu Z, Chen S, Hou L and Sakabe T: Preconditioning with hyperbaric oxygen and hyperoxia induces tolerance against spinal cord ischemia in rabbits. Anesthesiology. 96:907–912. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Wada K, Miyazawa T, Nomura N, Tsuzuki N, Nawashiro H and Shima K: Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus. Neurosurgery. 49:160–167. 2001.PubMed/NCBI

8 

Wang YC, Zhang S, Du TY, Wang B and Sun XQ: Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by stimulating autophagy in neurocyte. Brain Res. 1323:149–151. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J, et al: A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci USA. 107:11942–11947. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Pavare J, Grope I, Kalnins I and Gardovska D: High-mobility group box-1 protein, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study. BMC Infect Dis. 10:282010. View Article : Google Scholar

11 

Lotze MT, Zeh HJ, Rubartelli A, Sparvero LJ, Amoscato AA, Washburn NR, et al: The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev. 220:60–81. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Li Q and Verma IM: NF-kappaB regulation in the immune system. Nat Rev Immunol. 2:725–734. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Zdichavsky M, Jones JW, Ustuner ET, Ren X, Edelstein J, Maldonado C, et al: Scoring of skin rejection in a swine composite tissue allograft model. J Surg Res. 85:1–8. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Rongione AJ, Kusske AM, Kwan K, Ashley SW, Reber HA and McFadden DW: Interleukin 10 reduces the severity of acute pancreatitis in rats. Gastroenterology. 112:960–967. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Rosato E, Borghese F, Pisarri S and Salsano F: Laser Doppler perfusion imaging is useful in the study of Raynaud’s phenomenon and improves the capillaroscopic diagnosis. J Rheumatol. 36:2257–2263. 2009.PubMed/NCBI

16 

Wong HP, Zamboni WA and Stephenson LL: Effect of hyperbaric oxygen on skeletal muscle necrosis following primary and secondary ischemia in a rat model. Surg Forum. 47:705–707. 1996.

17 

Elktzschig HK and Collard CD: Vascular ischemia and reperfusion injury. Br Med Bull. 70:71–86. 2004. View Article : Google Scholar

18 

Aydogan H, Gurlek A, Parlakpinar H, Askar I, Bay-Karabulut A, Aydogan N, et al: Beneficial effects of caffeic acid phenethyl ester (CAPE) on the ischaemia-reperfusion injury in rat skin flaps. J Plast Reconstr Aesthet Surg. 60:563–568. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Feng GM, Yang WG, Huan-Tang CS, Chu YM, Tsai LM, Chang TM, et al: Periodic alterations of jejunal mucosa morphology following free microvascular transfer for pharyngoesophageal reconstruction. J Plast Reconstr Aesthet Surg. 59:1312–1317. 2006. View Article : Google Scholar

20 

Cetin C, Köse AA, Aral E, Colak O, Erçel C, Karabağli Y, et al: Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia reperfusion injury: experimental study in rat epigastric island flaps. Ann Plast Surg. 47:540–546. 2001. View Article : Google Scholar

21 

Tomur A, Etlik O and Gundogan NU: Hyperbaric oxygenation and antioxidant vitamin combination reduces ischemia-reperfusion injury in a rat epigastric island skin-flap model. J Basic Clin Physiol Pharmacol. 16:275–285. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Reichenberger MA, Heimer S, Schaefer A, Lass U, Gebhard MM, Germann G, et al: Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury. Stem Cell Rev. 8:854–862. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Kim CH, Choi H, Chun YS, Kim GT, Park JW and Kim MS: Hyperbaric oxygenation pretreatment induces catalase and reduces infarct size in ischemic rat myocardium. Pflugers Arch. 442:519–525. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Prass K, Wiegand F, Schumann P, Ahrens M, Kapinya K, Harms C, et al: Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent. Brain Res. 871:146–150. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Yamada T, Taguchi T, Hirata Y, Suita S and Yagi H: The protective effect of hyperbaric oxygenation on the small intestine in ischemia-reperfusion injury. J Pediatr Surg. 30:786–790. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Yu SY, Chiu JH, Yang SD, Yu HY, Hsieh CC, Chen PJ, et al: Preconditioned hyperbaric oxygenation protects the liver against ischemia-reperfusion injury in rats. J Surg Res. 128:28–36. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Li Y, Dong H, Chen M, Liu J, Yang L, Chen S, et al: Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral protection in patients undergoing coronary artery bypass graft surgery: a prospective, randomized, controlled clinical trial. J Cardiothorac Vasc Anesth. 25:908–916. 2011. View Article : Google Scholar

28 

Andrassy M, Volz HC, Igwe JC, Funke B, Eichberger SN, Kaya Z, et al: High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation. 117:3216–3226. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze MT, et al: The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med. 201:1135–1143. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Scaffidi P, Misteli T and Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 418:191–195. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al: HMG-1 as a late mediator of endotoxin lethality in mice. Science. 285:248–251. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, et al: High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 192:565–570. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Duan XF, Huang YM, Zhou YQ, Xu JJ and Zhang Q: Study of hyperbaric oxygenation on serum resistin and HMGB1 in patients with severe craniocerebral injury. Chin J Clinicians. 5:3189–3192. 2011.

34 

Chen YQ, Liu DH, Yang GT, et al: Expression of nuclear factor kappa B in rats after acute global cerebral ischemia-reperfusion and its significance. J Clin Res. 121:772–774. 2004.

35 

Qin C, Xiao YB, Zhong QJ, Chen L and Wang XF: Anti-inflammatory effect of erythropoietin pretreatment on cardiomyocytes with hypoxia/reoxygenation injury and the possible mechanism. Chin J Traumatol. 11:352–358. 2008.PubMed/NCBI

36 

Ghosh S and Baltimore D: Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 344:678–682. 1990. View Article : Google Scholar : PubMed/NCBI

37 

Wang L, Zhang X, Liu L, Cui L, Yang R, Li M, et al: Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression, ameliorates BBB permeability and endothelial cell function, and protects rat brains against focal ischemia. Brain Res. 1321:143–151. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Yang J, Li Y and Hu C: Ischemic preconditioning protects against myocardial ischemia-reperfusion injury through inhibiting toll-like receptor 4/NF-κB signaling pathway in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 36:972–978. 2011.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kang N, Hai Y, Liang F, Gao CJ and Liu XH: Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury. Mol Med Rep 9: 2124-2130, 2014.
APA
Kang, N., Hai, Y., Liang, F., Gao, C., & Liu, X. (2014). Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury. Molecular Medicine Reports, 9, 2124-2130. https://doi.org/10.3892/mmr.2014.2064
MLA
Kang, N., Hai, Y., Liang, F., Gao, C., Liu, X."Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury". Molecular Medicine Reports 9.6 (2014): 2124-2130.
Chicago
Kang, N., Hai, Y., Liang, F., Gao, C., Liu, X."Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury". Molecular Medicine Reports 9, no. 6 (2014): 2124-2130. https://doi.org/10.3892/mmr.2014.2064
Copy and paste a formatted citation
x
Spandidos Publications style
Kang N, Hai Y, Liang F, Gao CJ and Liu XH: Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury. Mol Med Rep 9: 2124-2130, 2014.
APA
Kang, N., Hai, Y., Liang, F., Gao, C., & Liu, X. (2014). Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury. Molecular Medicine Reports, 9, 2124-2130. https://doi.org/10.3892/mmr.2014.2064
MLA
Kang, N., Hai, Y., Liang, F., Gao, C., Liu, X."Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury". Molecular Medicine Reports 9.6 (2014): 2124-2130.
Chicago
Kang, N., Hai, Y., Liang, F., Gao, C., Liu, X."Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury". Molecular Medicine Reports 9, no. 6 (2014): 2124-2130. https://doi.org/10.3892/mmr.2014.2064
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team