Öz
Amaç: Bir dikarbonil bileşiği olan Metilglioksal (MG), hücresel metabolizmanın bir ürünü olarak normal veya patolojik koşullarda tüm hücrelerde bulunur. Kuersetinin antioksidan, anti-apoptotik ve nöroprotektif etkileri olduğu bilinmektedir. Bu çalışmanın amacı, kuersetinin nöron benzeri SH-SY5Y hücrelerinde metilglioksal kaynaklı toksisiteyi azaltıp azaltmadığını araştırmaktır.
Gereç ve Yöntem: MG'nin etkin toksik dozunu belirlemek için kültür ortamına farklı dozlarda (0-1000 µM) MG ilave edildi ve 24 saat inkübasyondan sonra MTT testi ile hücre canlılığı belirlendi. Daha sonra kuersetin (0.1 ve 1 µM), MG ile birlikte kültür ortamına verildi ve hücre canlılığı, hücre morfolojisi, apoptotik hücre ölümü, reaktif oksijen türlerinin oluşumu (ROS), total antioksidan kapasitesi (TAC) ve total oksidan stres (TOS) değerlendirildi.
Bulgular: MG, konsantrasyona bağlı olarak SH-SY5Y hücrelerinde hücre ölümünü artırdı. MG, hücrelerin morfolojik özelliklerinde önemli bozulmalara, apoptotik hücre ölümünün artmasına ve reaktif oksijen türlerinin oluşumuna neden oldu. Ayrıca toplam oksidan stres düzeyleri MG eklenen hücrelerde kontrole göre daha yüksek bulundu (p<0.005). MG ile birlikte kuersetin eklendiğinde hücre ölümü ve diğer tüm parametrelerde istatistiksel olarak anlamlı düzelme olduğu gözlendi.
Sonuç: Bu çalışmanın sonuçları, MG'nin insan SH-SY5Y hücreleri üzerinde doza bağımlı toksik etkiye sahip olduğunu ve bu toksik etkiden oksidatif hasarın sorumlu olabileceğini gösterdi. Ayrıca bulgular, kuersetinin MG ile indüklenen hücre hasarına karşı koruyucu etkilere sahip olabileceğini ortaya koydu.
Anahtar Kelimeler
Metilglioksal nörotoksisite oksidatif stres hücre ölümü kuersetin
Destekleyen Kurum
Yok
Proje Numarası
Yok
Teşekkür
Yok
Kaynakça
- Allaman I, Bélanger M, Magistretti P J. Methylglyoxal, the dark side of glycolysis. Front Neurosci 2015;9:1-12. doi:10.3389/fnins.2015.00023.
- Dhar I, Desai K. Aging: drugs to eliminate methylglyoxal, a reactive glucose metabolite, and advanced glycation endproducts. Pharmacology (Intechopen Book Series) 2012;30:681-708. doi:10.5772/34337.
- Nigro C, Leone A, Fiory F, Prevenzano I, Nicolò A, Mirra P, Beguinot F, Miele C. Dicarbonyl stress at the crossroads of healthy and unhealthy aging. Cells 2019;8(7):749. doi:10.3390/cells8070749.
- Degen J, Vogel M, Richter D, Hellwig M, Henle T. Metabolic transit of dietary methylglyoxal. J Agric Food Chem 2013;61(43):10253-60. doi:10.1021/jf304946p.
- Poulsen WM, Hedegaard VR, Andersen MJ, Courten B, Bügel S, Nielsen J, Skibsted HL, Dragsted OL. Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 2013;60:10-37. doi:10.1016/j.fct.2013.06.052.
- Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: A review. Diabetologia 2001;44 (2):129-46. doi: 10.1007/s001250051591.
- Egaña-Gorroño L, López-Díez R, Yepuri G, Ramirez LS, Reverdatto S, Gugger PF, Shekhtman A, Ramasamy R, Schmidt AM. Receptor for advanced glycation end products (rage) and mechanisms and therapeutic opportunities in diabetes and cardiovascular disease: insights from human subjects and animal models. Front Cardiovasc Med 2020;7:37. doi:10.3389/fcvm.2020.00037.
- Perrone A, Giovino A, Benny J, Martinelli F. Advanced glycation end products (ages): biochemistry, signaling, analytical methods, and epigenetic effects. Oxid Med Cell Longev. 2020;3818196. doi:10.1155/2020/3818196.
- Frandsen JR, Narayanasamy P. Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biol 2018;14:465-473. doi:10.1016/j.redox.2017.10.015.
- Huang X, Wang F, Chen W, Chen Y, Wang N, Von Maltzan K. Possible link between the cognitive dysfunction associated with diabetes mellitus and the neurotoxicity of methylglyoxal. Brain Res 2012;1469:82-91. doi:10.1016/j.brainres.2012.06.011.
- Wang Y, Ho CT. Flavour chemistry of methylglyoxal and glyoxal. Chem Soc Rev 2012;41 (11):4140-9. doi:10.1039/c2cs35025d.
- Rabbani N, Xue M, Thornalley PJ. Methylglyoxal-induced dicarbonyl stress in aging and disease: first steps towards glyoxalase 1-based treatments. Clin Sci (London) 2016;130(19):1677-96. doi:10.1042/CS20160025.
- Tavares JF, Ribeiro PVM, Coelho OGL, Silva LEd, Alfenas RCG. Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review. Obes Rev 2020;21(6):1-13. doi:10.1111/obr.1300.
- Shamsaldeen YA, Mackenzie LS, Lione LA, Benham CD. Methylglyoxal, a metabolite increased in diabetes is associated with insulin resistance, vascular dysfunction and neuropathies. Curr Drug Metab 2016;17(4):359- 67. doi:10.2174/1389200217666151222155216.
- Di Loreto S, Caracciolo V, Colafarina S, Sebastiani P, Gasbarri A, Amicarelli F. Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells. Brain Res 2004;1006(2):157–67. doi: 10.1016/j.brainres.2004.01.066
- Costa LG, Garrick JM, Roquè PJ, Pellacani C. Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxid Med Cell Longev 2016:2986796. doi:10.1155/2016/2986796.
- Pakrashi S, Chakraborty J, Bandyopadhyay J. Neuroprotective role of quercetin on rotenone-induced toxicity in SH-SY5Y cell line through modulation of apoptotic and autophagic pathways. Neurochem Res 2020;45(8):1962-73. doi:10.1007/s11064-020-03061-8.
- Velmurugan BK, Rathinasamy B, Lohanathan BP, Thiyagarajan V, Weng CF. Neuroprotective role of phytochemicals. Molecules 2018;23(10):1-15. doi:10.3390/molecules23102485
- Sharma S, Raj K, Singh S. Neuroprotective effect of quercetin in combination with piperine against rotenoneand iron supplement- induced Parkinson’s disease in experimental rats. Neurotox Res 2020;37(1):198-209. doi:10.1007/s12640-019-00120-z.
- Yang S, Zhou H, Wang G, Zhong XH, Shen QL, Zhang XJ, Li RY, Chen LH, Zhang YH, Wan Z. Quercetin is protective against short-term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice. J Food Biochem 2020;44(4):e13164. doi:10.1111/jfbc.13164.
- Khalilnezhad A, Taskiran D. The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity. Int J Neurosci 2019;129(5):481-91. doi:10.1080/00207454.2018.1543671.
- Erdoğan MA, Apaydin M, Armagan G, Taskiran D. Evaluation of toxicity of gadolinium-based contrast agents on neuronal cells. Acta Radiol 2021;62(2):206-14. doi:10.1177/0284185120920801.
- Lin H, Lin TY, Lin JA, Cheng KC, Santoso SP, Chou CH, Hsieh CW. Effect of pholiota nameko polysaccharides inhibiting methylglyoxal-induced glycation damage in vitro. Antioxidants (Basel) 2021;10(10):1589. doi:10.3390/antiox10101589.
- Suematsu N, Hosoda M, Fujimori K. Protective effects of quercetin against hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells. Neurosci Lett 2011;504(3):223-227. doi:10.1016/j.neulet.2011.09.028.
- Oguz E, Terzioglu Bebitoglu B, Acet G, Hodzic A, Hatiboglu N, Ada S. Effect of lycopene on As2O3 induced oxidative stress in SH-SY5Y cells. Mol Biol Rep 2021;48(4):3205-12. doi:10.1007/s11033-021-06377-y.
- Prestes A de S, dos Santos MM, Ecker A, Zanini D, Schetinger MRC, Rosemberg DB, Barbosa NV. Evaluation of methylglyoxal toxicity in human erythrocytes, leukocytes and platelets. Toxicol Mech Methods 2017;27(4):307-17. doi:10.1080/15376516.2017.1285971.
- Suzuki K, Koh YH, Mizuno H, Hamaoka R, Taniguchi N. Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone. J Biochem 1998;123(2):353-7. doi:10.1093/oxfordjournals.jbchem.a021944.
- Chun HJ, Lee Y, Kim AH, Lee J. Methylglyoxal causes cell death in neural progenitor cells and impairs adult hippocampal neurogenesis. Neurotox Res 2016;29(3):419-31. doi:10.1007/s12640-015-9588-y.
- Jeon JS, Kwon S, Ban K, Hong YK, Ahn C, Sung JS, Choi I. Regulation of the intracellular ROS level is critical for the antiproliferative effect of quercetin in the hepatocellular carcinoma cell line HepG2. Nutr Cancer 2019;71(5):861-9. doi:10.1080/01635581.2018.1559929.
- Liu YW, Liu XL, Kong L, Zhang MY, Chen YJ, Zhu X, Hao YC. Neuroprotection of quercetin on central neurons against chronic high glucose through enhancement of Nrf2/ARE/glyoxalase-1 pathway mediated by phosphorylation regulation. Biomed Pharmacother 2019;109:2145-54. doi:10.1016/j.biopha.2018.11.066.
- Ossola B, Kääriäinen TM, Raasmaja A, Männistö PT. Time-dependent protective and harmful effects of quercetin on 6-OHDA-induced toxicity in neuronal SH-SY5Y cells. Toxicology 2008;250(1):1-8. doi:10.1016/j.tox.2008.04.001.
- Bao D, Wang J, Pang X, Liu H. Protective effect of quercetin against oxidative stress-induced cytotoxicity in rat pheochromocytoma (PC-12) cells. Molecules 2017;22(7):1122. doi:10.3390/molecules22071122
Öz
Aim: Methylglyoxal (MG), a dicarbonyl compound, is found in all cells under normal or pathological conditions as a product of cellular metabolism. Quercetin is known to have antioxidant, anti-apoptotic and neuroprotective effects. The aim of the present study is to investigate whether quercetin reduces methylglyoxal-induced toxicity in neuron-like SH-SY5Y cells.
Materials and Methods: To determine the effective toxic dose of MG, different doses (0-1000 µM) of MG were added to the culture medium and cell viability was determined by MTT test after 24 hours of incubation. Then, quercetin (0.1 and 1 µM), was given to the culture medium together with MG, and cell viability, cell morphology, apoptotic cell death, formation of reactive oxygen species (ROS), total antioxidant capacity (TAC) and total oxidant stress (TOS) were evaluated.
Results: MG increased cell death in SH-SY5Y cells depending on the concentration. MG caused significant deterioration in the morphological features of the cells, increased apoptotic cell death and formation of reactive oxygen species. Also, total oxidant stress levels was found to be higher in the MG-added cells compared to the control (p<0.005). When quercetin was added together with MG, it was observed that there was a statistically significant improvement in cell death and all other parameters.
Conclusion: The results of this study demonstrated that MG has a dose-dependent toxic effect on human SH-SY5Y cells and oxidative damage may be responsible for this toxic effect. In addition, the findings showed that quercetin may have protective effects against MG-induced cell damage.
Anahtar Kelimeler
Methylglyoxal Neurotoxicity oxidative stress cell death quercetin
Proje Numarası
Yok
Kaynakça
- Allaman I, Bélanger M, Magistretti P J. Methylglyoxal, the dark side of glycolysis. Front Neurosci 2015;9:1-12. doi:10.3389/fnins.2015.00023.
- Dhar I, Desai K. Aging: drugs to eliminate methylglyoxal, a reactive glucose metabolite, and advanced glycation endproducts. Pharmacology (Intechopen Book Series) 2012;30:681-708. doi:10.5772/34337.
- Nigro C, Leone A, Fiory F, Prevenzano I, Nicolò A, Mirra P, Beguinot F, Miele C. Dicarbonyl stress at the crossroads of healthy and unhealthy aging. Cells 2019;8(7):749. doi:10.3390/cells8070749.
- Degen J, Vogel M, Richter D, Hellwig M, Henle T. Metabolic transit of dietary methylglyoxal. J Agric Food Chem 2013;61(43):10253-60. doi:10.1021/jf304946p.
- Poulsen WM, Hedegaard VR, Andersen MJ, Courten B, Bügel S, Nielsen J, Skibsted HL, Dragsted OL. Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 2013;60:10-37. doi:10.1016/j.fct.2013.06.052.
- Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: A review. Diabetologia 2001;44 (2):129-46. doi: 10.1007/s001250051591.
- Egaña-Gorroño L, López-Díez R, Yepuri G, Ramirez LS, Reverdatto S, Gugger PF, Shekhtman A, Ramasamy R, Schmidt AM. Receptor for advanced glycation end products (rage) and mechanisms and therapeutic opportunities in diabetes and cardiovascular disease: insights from human subjects and animal models. Front Cardiovasc Med 2020;7:37. doi:10.3389/fcvm.2020.00037.
- Perrone A, Giovino A, Benny J, Martinelli F. Advanced glycation end products (ages): biochemistry, signaling, analytical methods, and epigenetic effects. Oxid Med Cell Longev. 2020;3818196. doi:10.1155/2020/3818196.
- Frandsen JR, Narayanasamy P. Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biol 2018;14:465-473. doi:10.1016/j.redox.2017.10.015.
- Huang X, Wang F, Chen W, Chen Y, Wang N, Von Maltzan K. Possible link between the cognitive dysfunction associated with diabetes mellitus and the neurotoxicity of methylglyoxal. Brain Res 2012;1469:82-91. doi:10.1016/j.brainres.2012.06.011.
- Wang Y, Ho CT. Flavour chemistry of methylglyoxal and glyoxal. Chem Soc Rev 2012;41 (11):4140-9. doi:10.1039/c2cs35025d.
- Rabbani N, Xue M, Thornalley PJ. Methylglyoxal-induced dicarbonyl stress in aging and disease: first steps towards glyoxalase 1-based treatments. Clin Sci (London) 2016;130(19):1677-96. doi:10.1042/CS20160025.
- Tavares JF, Ribeiro PVM, Coelho OGL, Silva LEd, Alfenas RCG. Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review. Obes Rev 2020;21(6):1-13. doi:10.1111/obr.1300.
- Shamsaldeen YA, Mackenzie LS, Lione LA, Benham CD. Methylglyoxal, a metabolite increased in diabetes is associated with insulin resistance, vascular dysfunction and neuropathies. Curr Drug Metab 2016;17(4):359- 67. doi:10.2174/1389200217666151222155216.
- Di Loreto S, Caracciolo V, Colafarina S, Sebastiani P, Gasbarri A, Amicarelli F. Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells. Brain Res 2004;1006(2):157–67. doi: 10.1016/j.brainres.2004.01.066
- Costa LG, Garrick JM, Roquè PJ, Pellacani C. Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxid Med Cell Longev 2016:2986796. doi:10.1155/2016/2986796.
- Pakrashi S, Chakraborty J, Bandyopadhyay J. Neuroprotective role of quercetin on rotenone-induced toxicity in SH-SY5Y cell line through modulation of apoptotic and autophagic pathways. Neurochem Res 2020;45(8):1962-73. doi:10.1007/s11064-020-03061-8.
- Velmurugan BK, Rathinasamy B, Lohanathan BP, Thiyagarajan V, Weng CF. Neuroprotective role of phytochemicals. Molecules 2018;23(10):1-15. doi:10.3390/molecules23102485
- Sharma S, Raj K, Singh S. Neuroprotective effect of quercetin in combination with piperine against rotenoneand iron supplement- induced Parkinson’s disease in experimental rats. Neurotox Res 2020;37(1):198-209. doi:10.1007/s12640-019-00120-z.
- Yang S, Zhou H, Wang G, Zhong XH, Shen QL, Zhang XJ, Li RY, Chen LH, Zhang YH, Wan Z. Quercetin is protective against short-term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice. J Food Biochem 2020;44(4):e13164. doi:10.1111/jfbc.13164.
- Khalilnezhad A, Taskiran D. The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity. Int J Neurosci 2019;129(5):481-91. doi:10.1080/00207454.2018.1543671.
- Erdoğan MA, Apaydin M, Armagan G, Taskiran D. Evaluation of toxicity of gadolinium-based contrast agents on neuronal cells. Acta Radiol 2021;62(2):206-14. doi:10.1177/0284185120920801.
- Lin H, Lin TY, Lin JA, Cheng KC, Santoso SP, Chou CH, Hsieh CW. Effect of pholiota nameko polysaccharides inhibiting methylglyoxal-induced glycation damage in vitro. Antioxidants (Basel) 2021;10(10):1589. doi:10.3390/antiox10101589.
- Suematsu N, Hosoda M, Fujimori K. Protective effects of quercetin against hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells. Neurosci Lett 2011;504(3):223-227. doi:10.1016/j.neulet.2011.09.028.
- Oguz E, Terzioglu Bebitoglu B, Acet G, Hodzic A, Hatiboglu N, Ada S. Effect of lycopene on As2O3 induced oxidative stress in SH-SY5Y cells. Mol Biol Rep 2021;48(4):3205-12. doi:10.1007/s11033-021-06377-y.
- Prestes A de S, dos Santos MM, Ecker A, Zanini D, Schetinger MRC, Rosemberg DB, Barbosa NV. Evaluation of methylglyoxal toxicity in human erythrocytes, leukocytes and platelets. Toxicol Mech Methods 2017;27(4):307-17. doi:10.1080/15376516.2017.1285971.
- Suzuki K, Koh YH, Mizuno H, Hamaoka R, Taniguchi N. Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone. J Biochem 1998;123(2):353-7. doi:10.1093/oxfordjournals.jbchem.a021944.
- Chun HJ, Lee Y, Kim AH, Lee J. Methylglyoxal causes cell death in neural progenitor cells and impairs adult hippocampal neurogenesis. Neurotox Res 2016;29(3):419-31. doi:10.1007/s12640-015-9588-y.
- Jeon JS, Kwon S, Ban K, Hong YK, Ahn C, Sung JS, Choi I. Regulation of the intracellular ROS level is critical for the antiproliferative effect of quercetin in the hepatocellular carcinoma cell line HepG2. Nutr Cancer 2019;71(5):861-9. doi:10.1080/01635581.2018.1559929.
- Liu YW, Liu XL, Kong L, Zhang MY, Chen YJ, Zhu X, Hao YC. Neuroprotection of quercetin on central neurons against chronic high glucose through enhancement of Nrf2/ARE/glyoxalase-1 pathway mediated by phosphorylation regulation. Biomed Pharmacother 2019;109:2145-54. doi:10.1016/j.biopha.2018.11.066.
- Ossola B, Kääriäinen TM, Raasmaja A, Männistö PT. Time-dependent protective and harmful effects of quercetin on 6-OHDA-induced toxicity in neuronal SH-SY5Y cells. Toxicology 2008;250(1):1-8. doi:10.1016/j.tox.2008.04.001.
- Bao D, Wang J, Pang X, Liu H. Protective effect of quercetin against oxidative stress-induced cytotoxicity in rat pheochromocytoma (PC-12) cells. Molecules 2017;22(7):1122. doi:10.3390/molecules22071122
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | Yok |
| Yayımlanma Tarihi | 19 Mart 2024 |
| Gönderilme Tarihi | 9 Mayıs 2023 |
| Yayımlandığı Sayı | Yıl 2024Cilt: 63 Sayı: 1 |
Cited By
Methylglyoxal induces death in human brain neuronal cells (SH-SY5Y), prevented by metformin and dapagliflozin
Journal of Diabetes and its Complications
https://doi.org/10.1016/j.jdiacomp.2024.108832
