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Resveratrol Reorganizes the Impaired Cellular Functions of ARPE-19 Cells Created in Diabetes Model

Year 2025, Volume: 10 Issue: 1, 38 - 44
https://doi.org/10.26453/otjhs.1576093

Abstract

Objective: It is well known that high blood glucose levels can damage many visual functions. So, the study aimed to investigate the effects of resveratrol on cellular lipid peroxidation (MDA), cytokines, VEGF-A and apoptosis levels in vitro diabetes model-induced ARPE-19 cells.
Materials and Methods: Six experimental groups were conceptualized as follows. 1-Control group: Received no treatment (Standard Growth Medium), 2-Mannitol Group (M): Cells incubated in 19.5 mM Mannitol supplemented medium, 3-High Glucose Group (HG): Cells incubated in high glucose (25 mM Glucose), 4-Resveratrol Group (R): Cells incubated with 100 µM resveratrol Standard Growth Medium, 5-Mannitol + Resveratrol Group (M+R), 6-High Glucose + Resveratrol Group (HG+R). In All groups, cells were incubated for 48 hrs, and MDA, IL-1β, TNF-α, VEGF-A and Apoptosis levels were measured.
Results: High glucose medium increased the MDA, IL-1β, TNF-α and VEGF-A levels while resveratrol caused a significant decrement in MDA, IL-1β, TNF-α and VEGF-A levels in diabetes model-induced ARPE-19 cells. As a result, resveratrol prevented the ARPE-19 cells against diabetes related impaired conditions.
Conclusions: In conclusion, resveratrol can reverse disrupted cellular functions by reducing cellular oxidative stress and supporting cellular viability.

Ethical Statement

The authors state no conflict of interest.

Thanks

The authors thanks to technician Muhammet Şahin for his helps.

References

  • 1. Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018;19(6):1816. doi:10.3390/ijms19061816
  • 2. Sheemar A, Goel P, Thakur PS, et al. Diabetes, Diabetic Retinopathy, and Inflammatory Disorders. Ocul Immunol Inflamm. 2024;32(7):1155-1168. doi:10.1080/09273948.2023.2203742
  • 3. Kour V, Swain J, Singh J, Singh H, Kour H. A Review on Diabetic Retinopathy. Curr Diabetes Rev. 2024;20(6):e201023222418. doi:10.2174/0115733998253672231011161400
  • 4. Cioffi F, Adam RHI, Broersen K. Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer's Disease. J Alzheimers Dis. 2019;72(4):981-1017. doi:10.3233/JAD-190863
  • 5. Lu H, Chai J, Xu Z, et al. Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model. Zool Res. 2024;45(1):108-124. doi:10.24272/j.issn.2095-8137.2023.101
  • 6. Damay VA, Ivan I. Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression. Chin J Integr Med. 2024;30(10):927-937. doi:10.1007/s11655-024-3665-0
  • 7. Argun M, Tök L, Uğuz AC, Çelik Ö, Tök ÖY, Naziroğlu M. Melatonin and amfenac modulate calcium entry, apoptosis, and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation (405 nm). Eye (Lond). 2014;28(6):752-760. doi:10.1038/eye.2014.50
  • 8. Ma HZ, Chen Y, Guo HH, et al. Effect of resveratrol in gestational diabetes mellitus and its complications. World J Diabetes. 2023;14(6):808-819. doi:10.4239/wjd.v14.i6.808
  • 9. Santos MA, Franco FN, Caldeira CA, de Araújo GR, Vieira A, Chaves MM. Resveratrol has its antioxidant and anti-inflammatory protective mechanisms decreased in aging. Arch Gerontol Geriatr. 2023;107:104895. doi:10.1016/j.archger.2022.104895
  • 10. Arablou T, Aryaeian N, Khodaverdi S, et al. The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis. Sci Rep. 2021;11(1):6054. Published 2021 Mar 15. doi:10.1038/s41598-021-85512-y
  • 11. García-Layana A, Recalde S, Hernandez M, et al. A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration. Nutrients. 2021;13(4):1253. Published 2021 Apr 10. doi:10.3390/nu13041253
  • 12. Maugeri G, Bucolo C, Drago F, et al. Attenuation of High Glucose-Induced Damage in RPE Cells through p38 MAPK Signaling Pathway Inhibition. Front Pharmacol. 2021;12:684680. Published 2021 May 7. doi:10.3389/fphar.2021.684680
  • 13. Senol N, Nazıroğlu M. Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats. Neural Regen Res. 2014;9(11):1112-1116. doi:10.4103/1673-5374.135312
  • 14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275
  • 15. Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-364. doi:10.1016/0003-2697(66)90167-9
  • 16. Yıldızhan K, Nazıroğlu M. NMDA Receptor Activation Stimulates Hypoxia-Induced TRPM2 Channel Activation, Mitochondrial Oxidative Stress, and Apoptosis in Neuronal Cell Line: Modular Role of Memantine. Brain Res. 2023;1803:148232. doi:10.1016/j.brainres.2023.148232
  • 17. Öz A, Çelik Ö. The effects of neuronal cell differentiation on TRPM7, TRPM8 and TRPV1 channels in the model of Parkinson's disease. Neurol Res. 2022;44(1):24-37. doi:10.1080/01616412.2021.1952512
  • 18. King RE, Kent KD, Bomser JA. Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. Chem Biol Interact. 2005;151(2):143-149. doi:10.1016/j.cbi.2004.11.003
  • 19. Akbel E, Kucukkurt I, Ince S, et al. Investigation of protective effect of resveratrol and coenzyme Q10 against cyclophosphamide-induced lipid peroxidation, oxidative stress and DNA damage in rats. Toxicol Res (Camb). 2023;13(1):tfad123. Published 2023 Dec 30. doi:10.1093/toxres/tfad123
  • 20. Wang P, Yao Q, Zhu D, et al. Resveratrol protects against deoxynivalenol-induced ferroptosis in HepG2 cells. Toxicology. 2023;494:153589. doi:10.1016/j.tox.2023.153589
  • 21. Hashemzaei M, Tabrizian K, Alizadeh Z, et al. Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells. Toxicol Rep. 2020;7:1571-1577. Published 2020 Nov 23. doi:10.1016/j.toxrep.2020.11.008
  • 22. Lee WS, Shin JS, Jang DS, Lee KT. Cnidilide, an alkylphthalide isolated from the roots of Cnidium officinale, suppresses LPS-induced NO, PGE2, IL-1β, IL-6 and TNF-α production by AP-1 and NF-κB inactivation in RAW 264.7 macrophages. Int Immunopharmacol. 2016;40:146-155. doi:10.1016/j.intimp.2016.08.021
  • 23. Zhang W, Tang R, Ba G, Li M, Lin H. Anti-allergic and anti-inflammatory effects of resveratrol via inhibiting TXNIP-oxidative stress pathway in a mouse model of allergic rhinitis. World Allergy Organ J. 2020;13(10):100473. Published 2020 Oct 22. doi:10.1016/j.waojou.2020.100473
  • 24. Tanoğlu A, Özçelik F, Hacımustafaoğlu F, Coşkun G, Sapmaz T, Tanoğlu EG. Resveratrol has histone 4 and beta-defensin 1-mediated favorable biotherapeutic effects on liver and other target organs in diabetic rats. Turk J Gastroenterol. 2024;35(3):223-231. doi:10.5152/tjg.2024.23068
  • 25. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008;27(4):331-371. doi:10.1016/j.preteyeres.2008.05.001
  • 26. Ahmad A, Nawaz MI. Molecular mechanism of VEGF and its role in pathological angiogenesis. J Cell Biochem. 2022;123(12):1938-1965. doi:10.1002/jcb.30344
  • 27. Liu J, Li Y, Pu Q, Qiu H, Di D, Cao Y. A polysaccharide from Lycium barbarum L.: Structure and protective effects against oxidative stress and high-glucose-induced apoptosis in ARPE-19 cells. Int J Biol Macromol. 2022;201:111-120. doi:10.1016/j.ijbiomac.2021.12.139
  • 28. Tan J, Xiao A, Yang L, Tao YL, Shao Y, Zhou Q. Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina. World J Diabetes. 2024;15(3):519-529. doi:10.4239/wjd.v15.i3.519
  • 29. Yang Y, Zhang H, Liu Z, Zhao Z. Protective effect and mechanism of resveratrol on vascular endothelial cells. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024;36(6):664-668. doi:10.3760/cma.j.cn121430-20240103-00011
  • 30. Xiong F, Liu R, Guo H, Wu D, Sun N. Resveratrol alleviates Kawasaki disease-induced myocardial injury via inhibition of apoptosis and autophagy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021;46(10):1102-1108. doi:10.11817/j.issn.1672-7347.2021.200843

Resveratrol Diyabet Modeli Oluşturulmuş ARPE-19 Hücrelerinin Bozulmuş Hücre Fonksiyonlarini Yeniden Düzenler

Year 2025, Volume: 10 Issue: 1, 38 - 44
https://doi.org/10.26453/otjhs.1576093

Abstract

Amaç: Yüksek kan şekeri seviyelerinin birçok görsel fonksiyona zarar verebileceği bilinmektedir. Bu çalışmada resveratrolün in vitro diyabet modeli oluşturulan ARPE-19 hücrelerinin hücresel lipid peroksidasyonu (MDA), sitokinler, VEGF-A ve apoptoz seviyeleri üzerindeki etkileri amaçlanmıştır.
Materyal ve Metot: Altı deney grubu aşağıdaki şekilde oluşturulmuştur. 1-Kontrol grubu: Hiçbir tedavi uygulanmadı (Standart Büyütme Medyumu), 2-Mannitol Grubu (M): 19,5 mM mannitol takviyeli ortamda inkübe edilen hücreler, 3-Yüksek Glikoz Grubu (HG): Yüksek glikozda (25 mM Glikoz) inkübe edilen hücreler, 4-Resveratrol Grubu (R): Standart Büyütme Medyumunda ve 100 µM resveratrol ile inkübe edilen hücreler, 5-Mannitol + Resveratrol Grubu (M+R), 6-Yüksek Glikoz + Resveratrol Grubu (HG+R). Tüm gruplar 48 saat inkübasyon sonrasında MDA, IL-1β, TNF-α, VEGF-A ve Apoptozis düzeyleri ölçüldü.
Bulgular: Yüksek glikoz ortamı ARPE-19 hücrelerinde MDA, IL-1β, TNF-α ve VEGF-A seviyelerinde artışa neden olurken resveratrol, diyabet modeli oluşturulmuş hücrelerde MDA, IL-1β, TNF-α ve VEGF-A seviyelerinde önemli bir azalmaya neden olduğu görülmüştür. Sonuç olarak resveratrolün ARPE-19 hücrelerinin diyabet modeline bağlı olarak bozulmuş hücresel fonksiyonların düzeltilmesine yardımcı olduğu belirlenmiştir.
Sonuç: Resveratrol’ün hücresel oksidatif stresi azaltarak ve hücresel canlılığı destekleyerek bozulan hücresel fonksiyonları tersine çevirebileceği sonucuna varılmıştır.

References

  • 1. Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018;19(6):1816. doi:10.3390/ijms19061816
  • 2. Sheemar A, Goel P, Thakur PS, et al. Diabetes, Diabetic Retinopathy, and Inflammatory Disorders. Ocul Immunol Inflamm. 2024;32(7):1155-1168. doi:10.1080/09273948.2023.2203742
  • 3. Kour V, Swain J, Singh J, Singh H, Kour H. A Review on Diabetic Retinopathy. Curr Diabetes Rev. 2024;20(6):e201023222418. doi:10.2174/0115733998253672231011161400
  • 4. Cioffi F, Adam RHI, Broersen K. Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer's Disease. J Alzheimers Dis. 2019;72(4):981-1017. doi:10.3233/JAD-190863
  • 5. Lu H, Chai J, Xu Z, et al. Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model. Zool Res. 2024;45(1):108-124. doi:10.24272/j.issn.2095-8137.2023.101
  • 6. Damay VA, Ivan I. Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression. Chin J Integr Med. 2024;30(10):927-937. doi:10.1007/s11655-024-3665-0
  • 7. Argun M, Tök L, Uğuz AC, Çelik Ö, Tök ÖY, Naziroğlu M. Melatonin and amfenac modulate calcium entry, apoptosis, and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation (405 nm). Eye (Lond). 2014;28(6):752-760. doi:10.1038/eye.2014.50
  • 8. Ma HZ, Chen Y, Guo HH, et al. Effect of resveratrol in gestational diabetes mellitus and its complications. World J Diabetes. 2023;14(6):808-819. doi:10.4239/wjd.v14.i6.808
  • 9. Santos MA, Franco FN, Caldeira CA, de Araújo GR, Vieira A, Chaves MM. Resveratrol has its antioxidant and anti-inflammatory protective mechanisms decreased in aging. Arch Gerontol Geriatr. 2023;107:104895. doi:10.1016/j.archger.2022.104895
  • 10. Arablou T, Aryaeian N, Khodaverdi S, et al. The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis. Sci Rep. 2021;11(1):6054. Published 2021 Mar 15. doi:10.1038/s41598-021-85512-y
  • 11. García-Layana A, Recalde S, Hernandez M, et al. A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration. Nutrients. 2021;13(4):1253. Published 2021 Apr 10. doi:10.3390/nu13041253
  • 12. Maugeri G, Bucolo C, Drago F, et al. Attenuation of High Glucose-Induced Damage in RPE Cells through p38 MAPK Signaling Pathway Inhibition. Front Pharmacol. 2021;12:684680. Published 2021 May 7. doi:10.3389/fphar.2021.684680
  • 13. Senol N, Nazıroğlu M. Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats. Neural Regen Res. 2014;9(11):1112-1116. doi:10.4103/1673-5374.135312
  • 14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275
  • 15. Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-364. doi:10.1016/0003-2697(66)90167-9
  • 16. Yıldızhan K, Nazıroğlu M. NMDA Receptor Activation Stimulates Hypoxia-Induced TRPM2 Channel Activation, Mitochondrial Oxidative Stress, and Apoptosis in Neuronal Cell Line: Modular Role of Memantine. Brain Res. 2023;1803:148232. doi:10.1016/j.brainres.2023.148232
  • 17. Öz A, Çelik Ö. The effects of neuronal cell differentiation on TRPM7, TRPM8 and TRPV1 channels in the model of Parkinson's disease. Neurol Res. 2022;44(1):24-37. doi:10.1080/01616412.2021.1952512
  • 18. King RE, Kent KD, Bomser JA. Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. Chem Biol Interact. 2005;151(2):143-149. doi:10.1016/j.cbi.2004.11.003
  • 19. Akbel E, Kucukkurt I, Ince S, et al. Investigation of protective effect of resveratrol and coenzyme Q10 against cyclophosphamide-induced lipid peroxidation, oxidative stress and DNA damage in rats. Toxicol Res (Camb). 2023;13(1):tfad123. Published 2023 Dec 30. doi:10.1093/toxres/tfad123
  • 20. Wang P, Yao Q, Zhu D, et al. Resveratrol protects against deoxynivalenol-induced ferroptosis in HepG2 cells. Toxicology. 2023;494:153589. doi:10.1016/j.tox.2023.153589
  • 21. Hashemzaei M, Tabrizian K, Alizadeh Z, et al. Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells. Toxicol Rep. 2020;7:1571-1577. Published 2020 Nov 23. doi:10.1016/j.toxrep.2020.11.008
  • 22. Lee WS, Shin JS, Jang DS, Lee KT. Cnidilide, an alkylphthalide isolated from the roots of Cnidium officinale, suppresses LPS-induced NO, PGE2, IL-1β, IL-6 and TNF-α production by AP-1 and NF-κB inactivation in RAW 264.7 macrophages. Int Immunopharmacol. 2016;40:146-155. doi:10.1016/j.intimp.2016.08.021
  • 23. Zhang W, Tang R, Ba G, Li M, Lin H. Anti-allergic and anti-inflammatory effects of resveratrol via inhibiting TXNIP-oxidative stress pathway in a mouse model of allergic rhinitis. World Allergy Organ J. 2020;13(10):100473. Published 2020 Oct 22. doi:10.1016/j.waojou.2020.100473
  • 24. Tanoğlu A, Özçelik F, Hacımustafaoğlu F, Coşkun G, Sapmaz T, Tanoğlu EG. Resveratrol has histone 4 and beta-defensin 1-mediated favorable biotherapeutic effects on liver and other target organs in diabetic rats. Turk J Gastroenterol. 2024;35(3):223-231. doi:10.5152/tjg.2024.23068
  • 25. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008;27(4):331-371. doi:10.1016/j.preteyeres.2008.05.001
  • 26. Ahmad A, Nawaz MI. Molecular mechanism of VEGF and its role in pathological angiogenesis. J Cell Biochem. 2022;123(12):1938-1965. doi:10.1002/jcb.30344
  • 27. Liu J, Li Y, Pu Q, Qiu H, Di D, Cao Y. A polysaccharide from Lycium barbarum L.: Structure and protective effects against oxidative stress and high-glucose-induced apoptosis in ARPE-19 cells. Int J Biol Macromol. 2022;201:111-120. doi:10.1016/j.ijbiomac.2021.12.139
  • 28. Tan J, Xiao A, Yang L, Tao YL, Shao Y, Zhou Q. Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina. World J Diabetes. 2024;15(3):519-529. doi:10.4239/wjd.v15.i3.519
  • 29. Yang Y, Zhang H, Liu Z, Zhao Z. Protective effect and mechanism of resveratrol on vascular endothelial cells. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024;36(6):664-668. doi:10.3760/cma.j.cn121430-20240103-00011
  • 30. Xiong F, Liu R, Guo H, Wu D, Sun N. Resveratrol alleviates Kawasaki disease-induced myocardial injury via inhibition of apoptosis and autophagy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021;46(10):1102-1108. doi:10.11817/j.issn.1672-7347.2021.200843
There are 30 citations in total.

Details

Primary Language English
Subjects Vision Science
Journal Section Research article
Authors

Mehmet Argun 0000-0002-6877-4884

Ömer Çelik 0000-0002-9262-996X

Early Pub Date March 10, 2025
Publication Date
Submission Date October 30, 2024
Acceptance Date December 29, 2024
Published in Issue Year 2025 Volume: 10 Issue: 1

Cite

AMA Argun M, Çelik Ö. Resveratrol Reorganizes the Impaired Cellular Functions of ARPE-19 Cells Created in Diabetes Model. OTJHS. March 2025;10(1):38-44. doi:10.26453/otjhs.1576093

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