Quercetin'in 3T3-L1 olgun ve hipertrofik hücrelerde oksidatif stres üzerine etkisi

Yıl 2024, Cilt: 17 Sayı: 3, 578 - 586, 05.07.2024

Melek Tunç-ata , Emine Kılıç Toprak , Gizem Akan

https://doi.org/10.31362/patd.1497658

Öz

Amaç: Bütün dünyada sıklığı giderek artan obezite, vücutta aşırı veya anormal yağ birikmesi sürecidir. Oksidatif stres; serbest radikaller ve antioksidanlar arasındaki dengesizlik olup, bu durum obezitenin bir sonucu olabileceği gibi aynı zamanda obezitenin bir tetikleyicisi de olabilir. Obezite durumunda artan oksidatif stres, antioksidan kapasiteye sahip flavanoidler tarafından azaltılabilir. Bu araştırmanın amacı, olgun ve hipertrofik hale getirilmiş 3T3-L1 adipositlerde quercetinin oksidatif stres üzerine etkisinin belirlenmesidir.
Gereç ve yöntem: Önce farklılaştırılan ve daha sonra glikoz içeren medyum ve insülin ile muamele edilerek mature (10 gün) ve hipertrofik (18 gün) hale getirilen 3T3-L1 adipositleri 80 μM dozda quercetin (24saat, 48saat) ile inkübe edildi. Total antioksidan total oksidan kapasite (TAS/TOS) düzeyleri ELISA aracığılıyla ölçüldü. Oil Red O boyama ile hücrelerde oluşan trigliserit birikimi analiz edildi.
Bulgular: Sonuçlar quercetin molekülünün olgun adipositlerde oksidatif stres üzerine yalnızca TAS düzeyini arttırdığını gösterdi (TAS; M-C: 649,37±1,38; M-Q80: 655,87±1,68 p=0,0001), hipertrofik adipositlerde ise prooksidatif etki yaptığını gösterdi (OSI; H-C: 4,90±0,19; H-Q80: 6,20±0,039 p=0,0001).
Sonuç: Quercetin'in farklı yağ hücre türlerinde uygun doz ve sürede uygulanmasının çok sayıda yararlı etki üreten antioksidan etki mekanizması için belirleyici olduğuna inanılmaktadır.

Anahtar Kelimeler

Obezite, 3T3-L1 cell, quercetin, oksidatif stres, oksidan/antioksidan seviye

Effect of quercetin on oxidative stress in 3T3-L1 mature and hypertrophic cells

Öz

Purpose: The process of excessive or abnormal accumulation of fat in the body is called obesity, and its prevalence is increasing globally. The imbalance between antioxidants and free radicals, or oxidative stress, can be caused by or result from obesity. Flavonoids with antioxidant potential may help lower the increased oxidative stress associated with obesity. This study aimed to determine how quercetin affected oxidative stress in hypertrophied and mature 3T3-L1 adipocytes.
Materials and methods: After differentiating, 3T3-L1 adipocytes were treated with insulin and a glucose-containing medium to become mature (10 days) and hypertrophic (18 days). The cells were subsequently incubated with 80 μM quercetin for 24 and 48 hours. ELISA was used to determine the levels of total antioxidant total oxidant capacity (TAS/TOS). Using Oil Red O staining, an accumulation of triglycerides in cells was examined.
Results: The results showed that quercetin molecule only increased TAS level on oxidative stress in mature adipocytes (TAS; M-C: 649.37±1.38; M-Q80: 655.87±1.68 p=0.0001), whereas it exerted a prooxidative effect in hypertrophic adipocytes (OSI; H-C: 4.90±0.19; H-Q80: 6.20±0.039 p=0.0001).
Conclusion: It is believed that the administration of quercetin at the appropriate dose and duration in different fat cell types is crucial for the antioxidant mechanism of action that produces numerous beneficial effects.

Anahtar Kelimeler

Obesity, 3T3-L1 cell, quercetin, oxidative stress, oxidant/antioxidant level

Teşekkür

The authors thank Assist. Prof. Hande SENOL for her help in statistical analyses.

Kaynakça

• 1. Knights AJ, Funnell AP, Pearson RC, Crossley M, Bell-Anderson KS. Adipokines and insulin action: a sensitive issue. Adipocyte 2014;3:88-96. https://doi.org/10.4161/adip.27552
• 2. Horwitz A, Birk R. Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity. Nutrients 2023;15:3445. https://doi.org/10.3390/nu15153445
• 3. deFerranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. ClinChem 2008;54:945-955. https://doi.org/10.1373/clinchem.2007.100156
• 4. Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. J Cell Sci 2011;124:2681-2686. https://doi.org/10.1242/jcs.079699
• 5. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-1761. https://doi.org/10.1172/JCI21625
• 6. Blay M, Peinado-Onsurbe J, Julve J, et al. Anomalous lipoproteins in obese Zucker rats. Diabetes Obes Metab 2001;3:259-270. https://doi.org/10.1046/j.1463-1326.2001.00127.x
• 7. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014;105:141-150. https://doi.org/10.1016/j.diabres.2014.04.006
• 8. Concha F, Prado G, Quezada J, et al. Nutritional and non-nutritional agents that stimulate white adipose tissue browning. Rev Endocr Metab Disord 2019;20:161-171. https://doi.org/10.1007/s11154-019-09495-y
• 9. Carullo G, Cappello AR, Frattaruolo L, Badolato M, Armentano B, Aiello F. Quercetin and derivatives: useful tools in inflammation and pain management. Future Med Chem 2017;9:79-93. https://doi.org/10.4155/fmc-2016-0186 10. Eseberri I, Miranda J, Lasa A, Churruca I, Portillo MP. Doses of Quercetin in the Range of Serum Concentrations Exert Delipidating Effects in 3T3-L1 Preadipocytes by Acting on Different Stages of Adipogenesis, but Not in Mature Adipocytes. Oxid Med Cell Longev 2015;2015:480943. https://doi.org/10.1155/2015/480943
• 11. Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 2008;373:545-549. https://doi.org/10.1016/j.bbrc.2008.06.077
• 12. Bae CR, Park YK, Cha YS. Quercetin-rich onion peel extract suppresses adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 adipocytes. J Sci Food Agric 2014;94:2655-2660. https://doi.org/10.1002/jsfa.6604
• 13. Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 2011;12:722-734. https://doi.org/10.1038/nrm3198
• 14. Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975;5:19-27. https://doi.org/10.1016/0092-8674(75)90087-2
• 15. Li T, Zhang L, Jin C, Xiong Y, Cheng YY, Chen K. Pomegranate flower extract bidirectionally regulates the proliferation, differentiation and apoptosis of 3T3-L1 cells through regulation of PPARγ expression mediated by PI3K-AKT signaling pathway. Biomedicine & Pharmacotherapy 2020;131:110769. https://doi.org/10.1016/j.biopha.2020.110769
• 16. Büyükuslu N, Yiğitbaşı T. Reaktif oksijen türleri ve obezitede oksidatif stres. Clin Exp Health Sci 2015;5:197-203. https://doi.org/10.5455/musbed.20150604061607
• 17. Scalbert A, Manach C, Morand C, Rémésy C, Jiménez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287-306. https://doi.org/10.1080/1040869059096
• 18. Visioli F, Galli C. The role of antioxidants in the Mediterranean diet. Lipids 2001;36:S49-S52. https://doi.org/10.1007/s11745-001-0682-z
• 19. Malireddy S, Kotha SR, Secor JD, et al. Phytochemical antioxidants modulate mammalian cellula repigenome: implications in health and disease. Antioxid Redox Signal 2012;17:327-339. https://doi.org/10.1089/ars.2012.4600
• 20. Santangelo C, Varì R, Scazzocchio B, Di Benedetto R, Filesi C, Masella R. Polyphenols, intracellular signalling and inflammation. Ann Ist Super Sanita 2007;43:394-405.
• 21. Mishra A, Sharma AK, Kumar S, Saxena AK, Pandey AK. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities. Biomed Res Int 2013;915436. https://doi.org/10.1155/2013/915436
• 22. Leopoldini M, Russo N, Chiodo S, Toscano M. Iron chelation by the powerful antioxidant flavonoid quercetin. J Agric Food Chem 2006;54:6343-6351. https://doi.org/10.1021/jf060986h
• 23. Sharma UK, Sharma AK, Gupta A, Kumar R, Pandey A, Pandey AK. Pharmacological activities of cinnamaldehyde and eugenol: antioxidant, cytotoxic and anti-leishmanial studies. Cell Mol Biol 2017;63:73-78. https://doi.org/10.14715/cmb/2017.63.6.15
• 24. Gembe Olivarez G, Preciado Ortiz ME, Campos Perez W, Rodríguez Reyes SC, Martínez López E, Rivera Valdés JJ. A mix of ginger phenols exhibits anti adipogenic and lipolytic effects in mature adipocytes derived from 3T3 L1 cells. Exp Ther Med 2023;26:336. https://doi.org/10.3892/etm.2023.12035
• 25. Xiang W, Cheng S, Zhou Y, Ma L. Effects of 1,25(OH)2 D3 on lipid droplet growth in adipocytes. Biofactors 2020;46:943-954. https://doi.org/10.1002/biof.1610
• 26. Masschelin PM, Cox AR, Chernis N, Hartig SM. The Impact of Oxidative Stress on Adipose Tissue Energy Balance. Front Physiol 2020;1638. https://doi.org/10.3389/fphys.2019.01638
• 27. Dueñas M, González-Manzano S, González-Paramás A, Santos-Buelga C. Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin. J Pharm Biomed Anal 2010;51:443-449. https://doi.org/10.1016/j.jpba.2009.04.007
• 28. Justino GC, Santos MR, Canário S, Borges C, Florêncio MH, Mira L. Plasma quercetin metabolites: structure-antioxidant activity relationships. Arch Bio chem Biophys 2004;432:109-121. https://doi.org/10.1016/j.abb.2004.09.007
• 29. Gong M, Garige M, Varatharajalu R, et al. Quercetin up-regulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation. Biochem Biophys Res Commun 2009;379:1001-1004. https://doi.org/10.1016/j.bbrc.2009.01.015
• 30. Beatty ER, O'Reilly JD, England TG, et al. Effect of dietary quercetin on oxidative DNA damage in healthy human subjects. Br J Nutr 2000;84:919-925.
• 31. Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 2008;24:703-710. https://doi.org/10.1016/j.nut.2008.03.023
• 32. Abdelmoaty MA, Ibrahim MA, Ahmed NS, Abdelaziz MA. Confirmatory studies on the antioxidant and antidiabetic effect of quercetin in rats. Indian J Clin Biochem 2010;25:188-192. https://doi.org/10.1007/s12291-010-0034-x
• 33. Kılıçarslan G, Dönmez N. The effects of quercetin on antioxidant system and some blood parameters in experimental diabetic rats. Bull Env Pharmacol Life Sci 2016;5:28-32.
• 34. Boadi WY, Amartey PK, Lo A. Effect of quercetin, genistein and kaempferol on glutathione and glutathione-redoxcycle enzymes in 3T3-L1 preadipocytes. Drug Chem Toxicol 2016;39:239-247. https://doi.org/10.3109/01480545.2015.1082135
• 35. Noh HJ, Kim CS, Kang JH, et al. Quercetin suppresses MIP-1α-induced adipose inflammation by down regulating its receptors CCR1/CCR5 and inhibiting inflammatory signaling. J Med Food 2014;17:550–557. https://doi.org/10.1089/jmf.2013.2912
• 36. Robaszkiewicz A, Balcerczyk A, Bartosz G. Antioxidative and prooxidative effects of quercetin on A549 cells. Cell Biol Int 2007;31:1245-1250. https://doi.org/10.1016/j.cellbi.2007.04.009