Effects of the Topical Application of Cyclosporin A, Propolis and Dexamethasone on Oxidative Stress in Rats with Corneal Neovascularization

Year 2020, Volume: 5 Issue: 2, 271 - 280, 30.06.2020

İsa Yuvacı , Hayrullah Yazar

https://doi.org/10.26453/otjhs.718950

Cited By: 1

Abstract

Objective: To compare the effects of topical corneal inhibitory agents on total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidative stress index (OSI) levels in rats with experimentally acquired corneal neovascularization (CNV).
Materials and Methods: 35 Wistar male rats were divided into 5 Groups; Group I: 0.9% saline, Group II: 0.05% topical cyclosporine A, Group III: 1% topical propolis, Group IV: 3% topical propolis and Group V: 0.1% dexamethasone. CNV was formed with sodium hydroxide in the right eyes. All groups were treated 3/day for 10 days. Blood samples were taken from all of the rats.
Results: The TAC of the groups were 1.32, 1.22, 1.75, 1.27, and 1.37 μmol Trolox equivalent/L, respectively. The highest statistically significant increase in the TAC parameter was determined in Group III (p=0.041). TOC of the groups were 4.80, 6.0, 5.98, 6.09, and 10,32mmol H2O2 equivalent/L. The highest statistically significant increment of the TOC parameter was determined in Group V (p=0.041). OSI in the groups was 355.39, 494.63, 346.55, 477.18, and 746.48, respectively. Statistically significant increment of the OSI parameter was determined in GroupV (p=0.002).
Conclusion: Among these agents, 1% propolis was found to have the greatest effect on TAC. On the other hand, the use of Dexamethasone has caused a significant increase in OSI.

Keywords

oxidative stress, Cyclosporin A, dexamethasone, propolis

Thanks

This research was supported by Stj. Dr. F.E. Yazar, literature conformity (Bulent Ecevit University, Medical School) and Prof. Dr. O. Karabay, for the statistical study and revising it critically for important intellectual content (Sakarya University Medical School).

Topikal Siklosporin A, Propolis, ve Deksametazonun Korneal Neovaskülarisazyonlu Ratlarda Oksidatif Stres Üzerine Etkileri

Abstract

Amaç: Deneysel kornea neovaskülarizasyonu (KNV) oluşturulmuş ratlarda topikal kornea inhibe edici ajanların toplam antioksidan kapasite (TAK), toplam oksidan kapasite (TOK) ve oksidatif stres indeksi(OSİ) düzeyleri üzerindeki etkilerininin karşılaştırılması.
Materyal ve Metot: 35 Wistar erkek rat tedavilere göre 5 gruba ayrıldı. Grup I:% 0.9 salin, Grup II:% 0.05 topikal siklosporin A, GrupIII:% 1 topikal propolis, Grup IV:% 3 topikal propolis ve GrupV:% 0.1 deksametazon. KNV, ratların sağ gözlerinde sodyum hidroksit ile oluşturuldu. Bu uygulamadan 24 saat sonra tedaviler başlatıldı. Tüm gruplar 10 gün boyunca günde 3 kez tedavi edildi. Daha sonra tüm ratlardan kan örnekleri alındı. Tüm istatistiksel analizler IBM SPSS for Windows Version 20.0 yazılımı kullanılarak yapıldı.
Bulgular; TAK değerleri sırasıyla 1.32, 1.22, 1.75, 1.27 ve 1.37 μmol Trolox equivalent/L idi. TAK değerleri açısından en anlamlı artış Grup 3’te bulundu (p=0.041). TOK değerleri sırasıyla; 4.80, 6.0, 5.98, 6.09 ve 10,32 mmol H2O2 equivalent/L. idi. TOK değerleri açısından en anlamlı fark Grup 5’te bulundu (p=0.041). OSİ değerleri sırasıyla; 355.39, 494.63, 346.55, 477.18 ve746.48 idi. OSİ parametreleri açısından sadece Grup 5’te anlamlı fark ölçüldü (p=0.002).
Sonuç: Topikal korneal inhibitör ajanlar arasında % 1’lik propolisin TAK üzerinde önemli etkisinin olduğu, Deksametazon kullanımının OSİ'de önemli bir artışa neden olduğu bulundu.

Keywords

Deksametazon, oksidatif stress, propolis, siklosporin A

References

• 1. Lee P, Wang CC, Adamis AP. Ocular neovascularization. An epidemiologic review. Surv Ophthalmol. 1998;433:245-269.
• 2. Alldredge OC, Krachmer JH. Clinical types of corneal transplant rejection their manifestations, frequency, preoperative correlates, and treatment. Arch Ophthalmol. 1981;994:599-604.
• 3. Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001;124:242-249.
• 4. Boneham GC, Collin HB. Steroid inhibition of limbal blood and lymphatic vascular cell growth. Curr Eye Res. 1995;14:1–10.
• 5. Manzano RP, Peyman GA, Khan P, et al. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol. 2007;91:804–807.
• 6. Nakao S, Hata Y, Miura M, et al. Dexamethasone inhibits interleukin-1beta-induced corneal neovascularization: role of nuclear factor-kappaB-activated stromal cells in inflammatory angiogenesis. Am J Pathol. 2007;171:1058–1065.
• 7. Bian F, Wang C, Tukler-Henriksson J, et al. MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions. J Cell Physiol. 2016;231(11):2506-2516. doi: 10.1002/jcp.25364
• 8. Marcucci MC. Propolis: chemical composition, biological properties and therapeutic activity. Apidologie. 1995;26:83-99.
• 9. Nakajima Y, Shimazawa M, Mishima S, Hara H. Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions. Life Sci. 2007;80:370-377.
• 10. Burdock GA. Review of the biological properties and toxicity of bee propolis (Propolis). Food Chem Toxicol. 1988;36:347-363.
• 11. Hwang HJ, Park HJ, Chung, et al. Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. J Nutr Biochem. 2006;17: 356-362.
• 12. Hepsen IF, Er H, Cekic O. Topically applied water extract of propolis to suppress corneal neovascularization in rabbits. Ophthalmic Res. 1999;31:426-431.
• 13. Jin UH, Chunga TW, Kanga SK, et al. Caffeic acid phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9 and invasion inhibitor: isolation and identification. Clin Chim Acta. 2005;362:57-64.
• 14. Ahn MR, Kunimasa K, Ohta T, et al. Suppression of tumor-induced angiogenesis by Brazilian propolis: major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation. Cancer Lett. 2007;252(2):235-243.
• 15. Kimoto T, Arai Kohguchi M, Aga M, et al. Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis. Cancer Detect Prev. 1998;22:506-515.
• 16. Shimizua K, Dasa SK, Babab M, Matsuurac Y, Kanazawaa K. Dietary artepillin C suppresses the formation of aberrant crypt foci induced by azoxymethane in mouse colon. Cancer Lett. 2006;240:135-142.
• 17. Nussenblatt RB, Palestine AG. Cyclosporine: immunology, pharmacology, and therapeutic uses. Surv Ophthalmol. 1986;31:159-169.
• 18. Lutty GA, Liu SH, Pendergrast RA. Angiogenic lymphokines of activated T-cell origin. Invest Ophthalmol Vis Sci. 1983;24:1595-1601.
• 19. Heiligenhaus A, Steuhl KP. Treatment of HSV-1 stromal keratitis with topical cyclosporin A: a pilot study. Graefes Arch Clin Exp Ophthalmol. 1999;237:435–438.
• 20. Lipman RM, Epstein RJ, Hendricks RL. Suppression of corneal neovascularization with cyclosporine. Arch Ophthalmol. 1992;110: 405–407.
• 21. Benelli U, Ross JR, Nardi M, Klintworth GK. Corneal neovascularization induced by xenografts or chemical cautery. Inhibition by cyclosporin A. Invest Ophthalmol Vis Sci. 1997;38:274–282.
• 22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37:112-121.
• 23. Ates I, Ozkayar N, Topcuoglu C, Dede F. Relationship between oxidative stress parameters and asymptomatic organ damage in hypertensive patients without diabetes mellitus. Scand Cardiovasc J. 2015;49(5):249-56. doi: 10.3109/14017431.2015.1060355
• 24. Gunay S, Taskin A, Eser I, Yalcin S, Yalcin F. Oxidative stress and DNA damage due to one-lung ventilation. Ann Ital Chir. 2018;89:24-29.
• 25. Khazan M, Hedayati M, Robati RM, Riahi SM, Nasiri S. Impaired oxidative status as a potential predictor in clinical manifestations of herpes zoster. J Med Virol. 2018;28. doi: 10.1002/jmv.25204.
• 26. Bakunowicz-Łazarczyk A, Urban B. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation. Adv Med Sci. 2015;3;61(1):101-112. doi: 10.1016/j.advms.2015.10.003
• 27. Mirabelli P, Peebo BB, Xeroudaki M, Koulikovska M, Lagali N. Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Exp Eye Res. 2014;125:118-27. doi: 10.1016/j.exer.2014.06.006
• 28. Barichello T, Santos AL, Silvestre C, et al. Dexamethasone treatment reverses cognitive impairment but increases brain oxidative stress in rats submitted to pneumococcal meningitis. Oxid Med Cell Longev. 2011:173035. doi: 10.1155/2011/173035
• 29. Fasolo D, Bergold AM, von Poser G, Teixeira HF. Determination of benzophenones in lipophilic extract of Brazilian red propolis, nanotechnology-based product and porcine skin and mucosa: Analytical and bioanalytical assays. J Pharm Biomed Anal. 2016;124:57-66. doi: 10.1016/j.jpba.2016.02.018
• 30. Keshavarz M, Mostafaie A, Mansouri K, Shakiba Y, Motlagh HR. Inhibition of corneal neovascularization with propolis extract. Arch Med Res. 2009:40(1):59-61.