Protective Effects of Resveratrol Carbon Dots Against 6-OHDA-Induced Neurotoxicity in SH-SY5Y Cells

Öz

Background: We aimed to investigate the ability of resveratrol carbon dots (RES C-Dots) to protect SH-SY5Y cells from oxido-inflammatory stress and apoptosis caused by 6-hydroxydopamine (6-OHDA). Materials and Methods: In vitro PD model was generated in SH-SY5Y cells by administering of 200 µM 6-OHDA for 24 hours. Different concentrations of RES C-Dots (12.5, 25, and 50 µg/mL) were applied to the cells 30 minutes before administration of 6-OHDA. Results: We observed that application of RES C-Dots prevented cell death induced by 6-OHDA and main-tained cell viability. As expected, RES C-Dots prevented oxidative damage induced by 6-OHDA - by strengthening the total amount of antioxidants and lowering the total amount of oxidants in SH-SY5Y cells. Similarly, RES C-Dots markedly alleviated the secretion of inflammatory factors (TNF-α and IL-1β) promot-ed by 6-OHDA. Furthermore, RES C-Dots prevented apoptosis induced by 6-OHDA by suppressing caspase-3 mRNA expression level. Conclusions: RES C-Dots rescued SH-SY5Y cells from 6-OHDA- induced damage by modulating the oxido-inflammatory and apoptotic response. This report indicates enounces that RES- synthesised C-Dots may have promising curative potential for PD.

Anahtar Kelimeler

• Parkinson Disease
• 6-OHDA
• RES C-Dots
• SH-SY5Y cells

Resveratrol Karbon Noktalarının SH-SY5Y İnsan Nöroblastoma Hücrelerinde 6-OHDA Kaynaklı Nöronal Hücre Ölümü Üzerinde Koruyucu Etkileri

Öz

Amaç: Bu çalışmada Resveratrol karbon noktalarının (RES-KN) 6-OHDA'nın SH-SY5Y insan nöroblastoma hücrelerininde neden olduğu oksidoinflamatuar stres ve apoptozdan koruma potansiyelini araştırmayı amaçladık. Materyal ve Metod: SH-SY5Y hücreleri, in vitro PH modelini indüklemek için 24 saat boyunca 200 μM 6-OHDA'ya maruz bırakıldı. Hücrelere, 6-OHDA uygulamasından 30 dakika önce farklı konsantrasyonlarda RES KN (12.5, 25, and 50 µg/mL) uygulandı. Bulgular: Özellikle, RES KN uygulaması sonucu 6-OHDA'nın neden olduğu hücre ölümü etkili bir şekilde engellendiğini ve SH-SY5Y hücrelerinde hücre canlılığı önemli ölçüde korunduğunu gözlemledik. RES-KN, SH-SY5Y hücrelerinde toplam antioksidanları güçlendirerek ve toplam oksidanları düşürerek 6-OHDA kaynaklı oksidatif hasarı önledi. Benzer şekilde, RES-KN, 6-OHDA kaynaklı inflamatuvar faktörlerin (TNF-a ve IL-1β) salınımını önemli ölçüde azalttı. Ayrıca RES-KN, kaspaz-3 mRNA ekspresyonunu baskılayarak 6-OHDA’nın neden olduğu apoptozu engelledi. Sonuç: RES-KN’lar, oksido-inflamatuar ve apoptotik yanıtı modüle ederek SH-SY5Y hücrelerini 6-OHDA kaynaklı nörotoksisiteden kurtardı. Bu çalışma, RES’den sentezlenen KN’lerin PH tedavisinde umut verici terapötik potansiyele sahip olabileceğini düşündürmektedir.

Anahtar Kelimeler

• Parkinson's disease
• 6-OHDA
• RES C Dots
• SH-SY5Y cells

Kaynakça

1. 1. Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña, E. The chemistry of reactive oxygen species (ROS) revisited: outli-ning their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci, 2021;22(9): 42-63.
2. 2. Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Trajković, V. Graphene quantum dot antioxi-dant and proautophagic actions protect SH-SY5Y neuroblas-toma cells from oxidative stress-mediated apoptotic death. Free Radic Biol Med, 2021;177:167-180.
3. 3. Lee K H, Cha M, Lee BH. Crosstalk between neuron and glial cells in oxidative injury and neuroprotection. Int J Mol Sci, 2021;22(24):15-32.
4. 4. Mouchaileh N, & Hughes AJ. Pharmacological management of Parkinson’s disease in older people. J Pharm Pract Res, 2020; 50(5): 445-454.
5. 5. Ganesan P, Ko HM, Kim IS, & Choi DK. Recent trends in the development of nanophytobioactive compounds and deli-very systems for their possible role in reducing oxidative stress in Parkinson’s disease models. Int J Nanomedicine, 2015; 29(10):57-72.
6. 6. Dos Santos MG, Schimith LE, André-Miral C, Muccillo-Baisch AL, Arbo BD, & Hort M A. Neuroprotective effects of resve-ratrol in in vivo and in vitro experimental models of Parkin-son’s disease: A systematic review. Neurotox Res, 2022; 40:319–345.
7. 7. Zhang LF, Yu XL, Ji M, Liu SY, Wu XL, Wang YJ, et al. Resverat-rol alleviates motor and cognitive deficits and neuropatho-logy in the A53T α-synuclein mouse model of Parkinson's di-sease. Food Funct, 2018; 9(12): 6414-6426.
8. 8. Berman AY, Motechin RA, Wiesenfeld MY, & Holz MK. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol, 2017;1(1):35-46.

9. 9. Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, et al. Grap-hene quantum dots prevent α-synucleinopathy in Parkin-son’s disease. Nat Nanotechnol, 2018;13(9):812-818.
10. 10. Ben-Zichri S, Rajendran S, Bhunia SK, & Jelinek R. Resveratrol Carbon Dots Disrupt Mitochondrial Function in Cancer Cells. Bioconjug Chem, 2022;33(9):1663-1671.
11. 11. Xu X, Zhang K, Zhao L, Li C, Bu W, Shen Y, et al. Aspirin-based carbon dots, a good biocompatibility of material applied for bioimaging and anti-inflammation. ACS Appl Mater Interfa-ces, 2016; 8(48):32706-32716.
12. 12. Ferah Okkay I, Okkay U, Cicek B, Yilmaz A, Yesilyurt F, Mendil AS, et al. Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson’s di-sease. Mol Biol Rep, 2021:48;7711-7717.
13. 13. Tiong CX, Lu M, & Bian JS. Protective effect of hydrogen sulphide against 6‐OHDA‐induced cell injury in SH‐SY5Y cells involves PKC/PI3K/Akt pathway. Br J Pharmacol, 2010;161(2):467-480.
14. 14. Cicek B, & Danışman B. Cerium Oxide Nanoparticles Rescue Dopaminergic Neurons in Parkinson’s Disease Model of SH-SY5Y Cells via Modulating Nrf2 Signaling and Ameliorating Apoptotic Cell Death. ABC Research, 2023;5(2):284-290.
15. 15. Lee GH, Lee WJ, Hur J, Kim E, Lee HG., & Seo HG. Ginsenosi-de Re mitigates 6-hydroxydopamine-induced oxidative stress through upregulation of GPX4. Mol, 2020; 25(1):188-201.
16. 16. Raza C, & Anjum R. Parkinson's disease: Mechanisms, transla-tional models and management strategies. Life Sci, 2019; 226:77-90.
17. 17. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stab-le ABTS radical cation. Clin Biochem, 2004;37(4): 277-285.
18. 18. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 2005; 38(12):1103-1111.
19. 19. Leathem A, Simone M, Dennis JM, & Witting PK. The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inf-lammation in a Cell Model of Parkinson’s Disease. Antioxid, 2022:11(2);257-279.
20. 20. Kesh S, Kannan RR, Balakrishnan A. Naringenin alleviates 6-hydroxydopamine induced Parkinsonism in SHSY5Y cells and zebrafish model. Comp Biochem Physiol Part - C: Toxicol Pharmacol, 2021;239:1-7.
21. 21. Taylor JM, Main BS, & Crack PJ. Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkin-son’s disease. Neurochem Int, 2013; 62(5):803-819.
22. 22. Shao J, Liu X, Lian M, & Mao Y. Citronellol Prevents 6-OHDA-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Parkinson Disease Model of SH-SY5Y Cells via Modulating ROS-NO, MAPK/ERK, and PI3K/Akt Signaling Pathways. Neurotox Res, 2022; 40:1-17.
23. 23. Adebayo OG, Asiwe JN, Ben‐Azu B, Aduema W, Onyeleonu I, Akpotu AE, et al. Ginkgo biloba protects striatal neurodege-neration and gut phagoinflammatory damage in rotenone‐induced mice model of Parkinson's disease: Role of executi-oner caspase‐3/Nrf2/ARE signaling. J Food Biochem, 2022; 46(9):1-18.
24. 24. Ahmad MH, Fatima M, Ali M, Rizvi MA, & Mondal AC. Narin-genin alleviates paraquat-induced dopaminergic neuronal loss in SH-SY5Y cells and a rat model of Parkinson's disease. Neuropharmacology, 2021;201:1-14.
25. 25. Chen CH, Hsu PC, Hsu SW, Hong KT, Chen KY, He JL, et al. Protective Effects of Jujubosides on 6-OHDA-Induced Neuro-toxicity in SH-SY5Y and SK-N-SH Cells. Mol, 2022; 27(13):4106-4123.