Oxyresveratrolün, Deneysel Yaşa Bağli Makula Dejenerasyonunda Oksidatif Strese Karşi Koruyucu Etkisi
Year 2022,
Volume: 11 Issue: 3, 320 - 327, 30.12.2022
Cansu Kara Öztabağ
,
Akif Hakan Kurt
,
Lokman Ayaz
,
Mehmet Ali Sungur
Abstract
Amaç: Yaşa bağlı makula dejenerasyonu (YBMD), retina pigment epitel kompleksinin nörodejenerasyonunun neden olduğu görme kaybı ile karakterize kronik bir hastalıktır. Fazla oluşan reaktif oksijen türleri (ROS), makula dejenerasyonu başta olmak üzere retina hastalıklarının gelişmesinde önemli rol oynar. Başlıca ROS’lar ise; peroksinitritler, süperoksit radikaller ve hidrojen peroksitlerdir. Çalışmamızda hücre kültürü ortamında hidrojen peroksit (H2O2) ile oluşturulan oksidatif hasar öncesi oksiresveratrolün koruyucu etkisini araştırmayı amaçladık.
Gereç ve Yöntemler: İnsan retina pigment epitel (ARPE-19) hücrelerinde H2O2 ile oksidatif stres oluşturuldu. Oksidatif hasar öncesi oksiresveratrol 7 farklı konsantrasyonda uygulandı. Koruyucu etkiler, XTT hücre proliferasyonu testi ile hücre canlılığındaki değişiklik izlenerek araştırıldı. Oksiresveratrolün koruyucu etkisini moleküler düzeyde araştırmak için kaspaz-3 ve hücre ölüm tespit kiti kullanıldı.
Bulgular: Çalışmamızda ARPE-19 hücre hattında H2O2 ile oluşturulan oksidatif hasar öncesi oksiresveratrol uygulaması hücre canlılığını arttırarak hücrede oksidatif hasara karşı koruyucu etkinlik göstermiştir. Çalışmamız sonucunda elde ettiğimiz bulgularda; oksiresveratrol ARPE-19 hücrelerinde H2O2 ile oluşturulan oksidatif hasar oluşum öncesi uygulandığında 100 µM konsantrasyonda hücre hasarını yaklaşık %15 oranında azaltmıştır, buna ek olarak, hücre ölüm tespiti ve kaspaz-3 sonuçlarına göre, oksiresveratrolün oksidatif hasara karşı apoptotik hücre ölümünü azaltarak koruyucu etkinlik göstermektedir.
Sonuç: Bu in vitro çalışma oksiresveratrolün koruyucu etkisinin geliştirilmesi için ön çalışma niteliğindedir. Oksiresveratrol, deney hayvanları ve klinik çalışmalar sonrasında, başta YBMD olmak üzere retina hastalıklarının önlenmesinde etkin bir terapötik ajan olarak geliştirilebilir.
Supporting Institution
Bolu Abant İzzet Baysal Üniversitesi Bilimsel Araştırma Projeleri Birimi
Project Number
Proje numarası: 2020.08.36.1477
References
- Wang WL, Su X, Li X, Cheung CMG, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014; 2(2): e106-16.
- Ferris FL, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640-1642.
- Chiquita S, Rodrigues-Neves AC, Baptista FI, Carecho R, Moreira PI, Castelo-Branco M, et al. The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer's Disease: Critical Aspects to Unravel. Mol Neurobiol. 2019;56(8):5416-5435.
- Country MW. Retinal metabolism: a comparative look at energetics in the retina. Brain Res. 2017;1672:50–57.
- Cunha-Vaz J, Bernardes R, Lobo C. Blood-retinal barrier. European Journal of Ophthalmology. 2011;21(6):S3–S9.
- Campbell MI, Humphries P. The blood-retina barrier: tight junctions and barrier modulation. Advances in Experimental Medicine and Biology. 2012; 763:70–84.
- Ivanova E, Alam NM, Prusky GT, Sagdullaev BT. Blood-retina barrier failure and vision loss in neuron specific degeneration. JCI Insight. 2019;5:126747.
- Handa JH, Rickman CB, Dick AD, Gorin MB, Miller JW, Toth CA, et al. A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nat. Commun. 2019;10:3347.
- Jun S, Datta S, Wang L, Pegany R, Cano M, Handa JT. The impact of lipids, lipid oxidation, andinflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE. Exp. Eye Res. 2019;181:346–355.
- Dias MF, Joo K, Kemp JA, Fialho SL, Cunha AS, Woo SJ, et al. Molecular genetics andemerging therapies for retinitis pigmentosa: basic research and clinical perspectives. Prog Retin Eye Res. 2018;63:107-131.
- Shu W, Dunaief JL. Potential treatment of retinal diseases with iron chelators. Pharmaceuticals. 2018;11:E112.
- Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004;122(4):598-614.
- Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997;104(1):7-21.
- Abdelsalam A, Priore LD, Zarbin MA. Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol. 1999;44(1):1-29.
- Parmet S, Lynm C, Glass RM. Age-related macular degeneration. JAMA. 2006;295(20):2438.
- Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium.. Eye. 1988;2(5):552–577.
- Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: a review.. Clinical interventions in aging. 2017;12:1313.
- Karaçorlu SA, Karaçorlu M. Makula hastalıkları. In 0’Dwyer PA AY, editor. Temel Göz Hastalıkları.: Güneş Tıp Kitabevleri; 2010. p.559-573.
- Li J, Wuliji O, Li W, Jiang ZG, Ghanbari HA. Oxidative stress and neurodegenerative disorders. International Journal of Molecular Sciences. 2013;14(12):24438–24475.
- Pham-Huy LA, He H, Pham-Huyc C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 2008;4(2):89-96.
- Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;266(1-2):37-56.
- Halliwell B, Gutteridge JM. The antioxidants of human extracellular fluids. Arch Biochem Biophys. 1990;280:1-8.
- Dutta S, Parames SM. Phytoestrogens as Novel Therapeutic Molecules Against Breast Cancer. Natural Product Drug Discovery. 2021;197-229.
- Likhitwitayawuid K, Sornsute A, Sritularak B, Ploypradith P. Chemical transformations of oxyresveratrol ( trans -2,4,3 ,5 -tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent. Bioorg Med Chem Lett. 2006;16:5650–5653.
- Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an Internationalforum on cardiac remodeling.. J Am Coll Cardiol. 2000;35(3):569-82.
- Chung, KO., Kim, BY., Lee, MH., Kim, YR., Chung, HY., Park, JH., Moon, JO. In-vitro and in-vivo anti inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol. 2003;55(55):1695-700.
- Andrabi SA, Spina MG, Lorenz P, Ebmeyer U, Wolf G, Horn TF. Oxyresveratrol ( t rans-2,3, 4 ,5tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic the apoptotic cell death in transient cerebral ischemia. Brain Res. 2004;13:98-107.
- Lipipun V, Sasivimolphan P, Yoshida Y, Daikoku T, Sritularak B, Ritthidej G, et al. Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antiviral Research. 91(2):154–160.
- Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ. Cell Viability Assays. In n: Markossian S GE. Assay Guidance Manual [Internet].: Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2016.
- Gordois A, Cutler H, Pezzullo L. An estimation of the worldwide economic and health burden of visual impairment. Global Public Health. 2012;7(5):465–481.
- Stahl A. The diagnosis and treatment of age-related macular degeneration. Dtsch Arztebl Int. 2020;117:513-9.
- Likhitwitayawuid KB, Sritularak K, Benchanak V, Lipipun J, Schinazi RF. Phenolics with antiviral activity from Millettia erythrocalyx and Artocarpus lakoocha. Natural Product Research. 2005;19(2):177–182.
- Hu X, Liang Y, Zhao B, Wang Y. Oxyresveratrol protects human lens epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis by activation of Akt/HO-1 pathway. Journal of Pharmacological Sciences. 2019;166-173.
- Lorenz P, Roychowdhury S, Engelmann M, Wolf G, Horn TFW. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: Effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide. 2003;9:64–76.
- Crompton M. Mitochondria and aging: a role for the permeability transition? Aging Cell. 2004;3:3-6.
- Ban JY, Cho SO, Choi SH, Yeon HSJ, Bae KH, Song KS, et al. Neuroprotective Effect of Smilacis chinae Rhizome on NMDA-Induced. Journal of Pharmacological Sciences. 2007;106:68-77.
- Chao J, Yu MS, Ho YS, Wang M, Chang RCC. Dietary oxyresveratrol prevents parkinsonian mimetic. Free Radical Biology & Medicine. 2008;45:1019–1026.
Protectıve Effect Of Oxyresveratrol Agaınst Oxıdatıve Stress In Experımental Age-Related Macula Degeneratıon
Year 2022,
Volume: 11 Issue: 3, 320 - 327, 30.12.2022
Cansu Kara Öztabağ
,
Akif Hakan Kurt
,
Lokman Ayaz
,
Mehmet Ali Sungur
Abstract
Objective: Age-related-macular-degeneration (AMD) is a chronic disease characterized by vision loss caused by neurodegeneration of the retinal pigment epithelial complex. Excess reactive oxygen species(ROS) play an important role in the development of retinal diseases, especially macular degeneration. The main ROS are; peroxynitrides, superoxide radicals and hydrogen peroxides. In our study, we aimed to investigate the protective effect of before oxidative damage induced by hydrogen peroxide(H2O2) in cell culture.
Materials and Methods: Oxidative stress was induced with H2O2 in human retinal pigment epithelial(ARPE-19) cells. Oxyresveratrol was applied at 7 different concentrations before oxidative damage. Protective effects were investigated by monitoring the change in cell viability with the XTT cell proliferation assay. Caspase-3 and cell-death-detection kit were used to investigate the protective effect of oxyresveratrol and its molecular mechanism.
Results: In our study, oxyresveratrol application before oxidative damage induced by H2O2 in ARPE-19 cell line increased cell viability and showed protective activity against oxidative damage in the cell. In the findings we obtained as a result of our study; When oxyresveratrol was applied to ARPE-19 cells before the oxidative damage induced by H2O2, it reduced cell damage by about 15% at 100 µM concentration. In addition, according to cell death detection and caspase-3 results, oxyresveratrol showed protective activity against oxidative damage by reducing apoptotic cell death.
Conclusion: This in vitro study is a preliminary study for the development of the protective effect of oxyresveratrol. Oxyresveratrol can be developed as an effective therapeutic agent in the prevention of retinal diseases, especially AMD, after experimental animals and clinical studies.
Project Number
Proje numarası: 2020.08.36.1477
References
- Wang WL, Su X, Li X, Cheung CMG, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014; 2(2): e106-16.
- Ferris FL, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640-1642.
- Chiquita S, Rodrigues-Neves AC, Baptista FI, Carecho R, Moreira PI, Castelo-Branco M, et al. The Retina as a Window or Mirror of the Brain Changes Detected in Alzheimer's Disease: Critical Aspects to Unravel. Mol Neurobiol. 2019;56(8):5416-5435.
- Country MW. Retinal metabolism: a comparative look at energetics in the retina. Brain Res. 2017;1672:50–57.
- Cunha-Vaz J, Bernardes R, Lobo C. Blood-retinal barrier. European Journal of Ophthalmology. 2011;21(6):S3–S9.
- Campbell MI, Humphries P. The blood-retina barrier: tight junctions and barrier modulation. Advances in Experimental Medicine and Biology. 2012; 763:70–84.
- Ivanova E, Alam NM, Prusky GT, Sagdullaev BT. Blood-retina barrier failure and vision loss in neuron specific degeneration. JCI Insight. 2019;5:126747.
- Handa JH, Rickman CB, Dick AD, Gorin MB, Miller JW, Toth CA, et al. A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nat. Commun. 2019;10:3347.
- Jun S, Datta S, Wang L, Pegany R, Cano M, Handa JT. The impact of lipids, lipid oxidation, andinflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE. Exp. Eye Res. 2019;181:346–355.
- Dias MF, Joo K, Kemp JA, Fialho SL, Cunha AS, Woo SJ, et al. Molecular genetics andemerging therapies for retinitis pigmentosa: basic research and clinical perspectives. Prog Retin Eye Res. 2018;63:107-131.
- Shu W, Dunaief JL. Potential treatment of retinal diseases with iron chelators. Pharmaceuticals. 2018;11:E112.
- Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004;122(4):598-614.
- Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997;104(1):7-21.
- Abdelsalam A, Priore LD, Zarbin MA. Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol. 1999;44(1):1-29.
- Parmet S, Lynm C, Glass RM. Age-related macular degeneration. JAMA. 2006;295(20):2438.
- Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium.. Eye. 1988;2(5):552–577.
- Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: a review.. Clinical interventions in aging. 2017;12:1313.
- Karaçorlu SA, Karaçorlu M. Makula hastalıkları. In 0’Dwyer PA AY, editor. Temel Göz Hastalıkları.: Güneş Tıp Kitabevleri; 2010. p.559-573.
- Li J, Wuliji O, Li W, Jiang ZG, Ghanbari HA. Oxidative stress and neurodegenerative disorders. International Journal of Molecular Sciences. 2013;14(12):24438–24475.
- Pham-Huy LA, He H, Pham-Huyc C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. 2008;4(2):89-96.
- Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;266(1-2):37-56.
- Halliwell B, Gutteridge JM. The antioxidants of human extracellular fluids. Arch Biochem Biophys. 1990;280:1-8.
- Dutta S, Parames SM. Phytoestrogens as Novel Therapeutic Molecules Against Breast Cancer. Natural Product Drug Discovery. 2021;197-229.
- Likhitwitayawuid K, Sornsute A, Sritularak B, Ploypradith P. Chemical transformations of oxyresveratrol ( trans -2,4,3 ,5 -tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent. Bioorg Med Chem Lett. 2006;16:5650–5653.
- Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an Internationalforum on cardiac remodeling.. J Am Coll Cardiol. 2000;35(3):569-82.
- Chung, KO., Kim, BY., Lee, MH., Kim, YR., Chung, HY., Park, JH., Moon, JO. In-vitro and in-vivo anti inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol. 2003;55(55):1695-700.
- Andrabi SA, Spina MG, Lorenz P, Ebmeyer U, Wolf G, Horn TF. Oxyresveratrol ( t rans-2,3, 4 ,5tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic the apoptotic cell death in transient cerebral ischemia. Brain Res. 2004;13:98-107.
- Lipipun V, Sasivimolphan P, Yoshida Y, Daikoku T, Sritularak B, Ritthidej G, et al. Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antiviral Research. 91(2):154–160.
- Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ. Cell Viability Assays. In n: Markossian S GE. Assay Guidance Manual [Internet].: Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2016.
- Gordois A, Cutler H, Pezzullo L. An estimation of the worldwide economic and health burden of visual impairment. Global Public Health. 2012;7(5):465–481.
- Stahl A. The diagnosis and treatment of age-related macular degeneration. Dtsch Arztebl Int. 2020;117:513-9.
- Likhitwitayawuid KB, Sritularak K, Benchanak V, Lipipun J, Schinazi RF. Phenolics with antiviral activity from Millettia erythrocalyx and Artocarpus lakoocha. Natural Product Research. 2005;19(2):177–182.
- Hu X, Liang Y, Zhao B, Wang Y. Oxyresveratrol protects human lens epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis by activation of Akt/HO-1 pathway. Journal of Pharmacological Sciences. 2019;166-173.
- Lorenz P, Roychowdhury S, Engelmann M, Wolf G, Horn TFW. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: Effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide. 2003;9:64–76.
- Crompton M. Mitochondria and aging: a role for the permeability transition? Aging Cell. 2004;3:3-6.
- Ban JY, Cho SO, Choi SH, Yeon HSJ, Bae KH, Song KS, et al. Neuroprotective Effect of Smilacis chinae Rhizome on NMDA-Induced. Journal of Pharmacological Sciences. 2007;106:68-77.
- Chao J, Yu MS, Ho YS, Wang M, Chang RCC. Dietary oxyresveratrol prevents parkinsonian mimetic. Free Radical Biology & Medicine. 2008;45:1019–1026.