Kurkuminin Fruktoza İndüklenmiş Metabolik Sendromlu Sıçan Modelleri Üzerindeki Etkisinin İncelenmesi

Öz

Amaç: Çalışmamızda, fruktoza bağlı metabolik sendrom sıçan modelinde kurkuminin glukoz homeostazı, insülin direnci, inflamasyon ve oksidatif stres üzerindeki olası etkilerinin değerlendirmesini amaçladık. Gereç ve Yöntemler: 24 adet erkek erişkin Wistar albino rat rastgele 4 gruba ayrıldı: kontrol (Grup 1), %20 fruktoz (Grup 2), %20 fruktoz ve 100 mg/kg kurkumin (Grup 3) ve %20 fruktoz, ve 200 mg/kg kurkumin (Grup 4). Serum glukoz, insülin ve plazma lipoprotein seviyeleri otoanalizör tarafından belirlenmiştir. Diğer parametreler ise Elisa Assay Metodu ile incelenmiştir. İki grup arasındaki farkın anlamlılığını belirlemek için Mann-Whitney U testi kullanılarak Bonferroni Düzeltmesi yapılmıştır (p≤0,008). Parametreler arasında ise Spearman Korelasyon Analizi yapılmıştır Bulgular: Grup 2'de Grup 1'e göre artan serum glukozu, yüksek tansiyon, insülin direnci ve dislipidemi gözlenerek Metabolik Sendrom (MetS) başarıyla oluşturulmuştur (p≤0,008). Gruplar arasında serum total antioksidan kapasite (TAC) düzeylerinde farkın anlamlılığı bulunamamıştır. Grup 2'nin serum total oksidan durum (TOS) ve oksidatif stres indeksi (OSI) seviyeleri Grup 1'e göre anlamlı olarak artarken, Grup 3 ve Grup 4'te Grup 2'ye göre bu parametrelerin düzeyleri anlamlı olarak azalmıştır (p≤0,008). Grup 2'nin serum tümör nekrozis faktör-α (TNF-α) düzeyi Grup 1'e göre anlamlı düzeyde artmıştır (p≤0,008). Grup 3 ve Grup 4'ün serum TNF-α düzeyinin Grup 2'ye göre anlamlı düzeyde düştüğü belirlenmiştir (p≤ 0,008). Serum OSI ve TNF-α düzeyleri ile serum HOMA-IR ve TNF-α düzeyleri arasında pozitif korelasyon saptanmıştır (p≤0,01). Sonuç: Bulgularımız, sıçan deneysel hayvan modelinde kurkuminin MetS'e karşı iyileştirici bir etkiye sahip olduğunu göstermiştir

Anahtar Kelimeler

• metabolik sendrom
• insülin direnci
• oksidatif stres

An Investigation of the Effect of Curcumin on Fructose-Induced Metabolic Syndrome Rat Models

Öz

Aim: This study aimed to evaluate the potential effect of curcumin on glucose homeostasis, insulin resistance, inflammation, and oxidative stress in a fructose-induced metabolic syndrome rat model. Material and Methods: 24 male adult Wistar albino rats were randomly separated in to 4 groups: control (Group 1), 20% fructose (Group 2), 20% fructose and 100 mg/kg curcumin (Group 3), and 20% fructose, and 200 mg/kg curcumin (Group 4). Serum glucose, insulin, and plasma lipoprotein levels were determined by an auto-analyzer. Other parameters were determined by the Elisa Assay Method. Mann-Whitney U test was performed using the Bonferroni Correction to determine the significance of the difference between the two group (p≤0.008). Spearman Correlation Analysis was performed among parameters. Results: Metabolic Syndrome (MetS) was successfully created by observing increased serum glucose, high blood pressure, insulin resistance, and dyslipidemia in Group 2 compared to Group 1 (p≤0.008). The significance of serum total antioxidant capacity (TAC) levels among the groups could not be determined. While serum total oxidant status (TOS) and oxidative stress index (OSI) levels of Group 2 increased significantly compared to Group 1, and the levels of these parameters were significantly decreased in Group 3 and Group 4 compared to Group 2 (p≤0.008). The serum tumor necrosis factor-α (TNF-α) level of Group 2 increased significantly compared to Group 1 (p≤0.008). It was determined that the serum TNF-α level of Group 3 and Group 4 decreased significantly compared to Group 2 (p≤0.008). There was a positive correlation between serum OSI and TNF-α levels and serum HOMA-IR and TNF-α levels (p≤0.01). Conclusion: Our findings indicated that curcumin has a healing effect against MetS in the rat experimental animal model.

Anahtar Kelimeler

• Metabolic syndrome
• insulin resistance
• oxidative stress
• inflammation

Kaynakça

1. 1. Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond). 2005;2(1):5.
2. 2. Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Zachariah B. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases. Chem Biol Interact. 2016;244:187-194.
3. 3. Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life Sci. 2009;84(21-22):705-712.
4. 4. Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress. Can J Physiol Pharmacol. 2017;95(2):140-150.
5. 5. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23(1A):363-398.
6. 6. Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol. 2014;39:113-204.
7. 7. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40-59.
8. 8. Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental-Mendía LE, Majeed M, Sahebkar A. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomed Pharmacother. 2016;82:578-582.

9. 9. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, Saengsuwan J, Tantayakom K, Laongpech S. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451-458.
10. 10. Mazzolani F, Togni S. Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study. Clin Ophthalmol. 2013;7:939-945.
11. 11. Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol. 2010;4:1201-1206.
12. 12. Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol. 2017;174(11):1290-1324.
13. 13. Perrone D, Ardito F, Giannatempo G, Dioguardi M, Troiano G, Lo Russo L, DE Lillo A, Laino L, Lo Muzio L. Biological and therapeutic activities, and anticancer properties of curcumin. Exp Ther Med. 2015;10(5):1615-1623.
14. 14. Stanic Z. Electrochemical investigation of some biological important compounds correlated to curcumin. In Curcumin: biosynthesis, medicinal uses and health benefits 10th Edition, New York, Nova Science Publisher, 2012
15. 15. Ferguson JJA, Stojanovski E, MacDonald-Wicks L, Garg ML. Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial. Metabolism. 2018;82:22-35.
16. 16. Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Zachariah B. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases. Chem Biol Interact. 2016 25;244:187-194.
17. 17. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):1059-1062.
18. 18. Pan Y, Zhao D, Yu N, An T, Miao J, Mo F, Gu Y, Zhang D, Gao S, Jiang G. Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes. R Soc Open Sci. 2017;4(11):170917.
19. 19. Yao Y, Wang W, Li M, Ren H, Chen C, Wang J, Wang WE, Yang J, Zeng C. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells. Sci Rep. 2016;6:25579.
20. 20. Bernardis LL, Patterson BD. Correlation between 'Lee index' and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol. 1968;40(4):527-528.
21. 21. Xydakis AM, Case CC, Jones PH, Hoogeveen RC, Liu MY, Smith EO, Nelson KW, Ballantyne CM. Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. J Clin Endocrinol Metab. 2004;89(6):2697-2703.
22. 22. Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17.
23. 23. Welty FK, Alfaddagh A, Elajami TK. Targeting inflammation in metabolic syndrome. Transl Res. 2016;167(1):257-280.
24. 24. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006;290(3):F625-F631.
25. 25. Kantar Ş, Türközkan N, Bircan FS, Paşaoğlu ÖT. Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats. Pharm Biol. 2015;53(7):1035-1041.
26. 26. Yilmaz Demirtas C, Bircan FS, Pasaoglu OT, Turkozkan N. The effects of resveratrol on hepatic oxidative stress in metabolic syndrome model induced by high fructose diet. Bratisl Lek Listy. 2018;119(1):36-40.
27. 27. Pasaoglu OT, Bircan FS, Topal T, Turkozkan N. Positive Effects of Melatonin on Renal Nitric Oxide-Asymmetric Dimethylarginine Metabolism in Fructose-Fed Rats. Metab Syndr Relat Disord. 2021;19(3):120-126.
28. 28. Kohli K, Ali J, Ansari MJ, Raheman Z. Curcumin: a natural antiinflammatory agent. Indian Journal of Pharmacology, 2005;37(3):141.
29. 29. Maithili Karpaga Selvi N, Sridhar MG, Swaminathan RP, Sripradha R. Curcumin Attenuates Oxidative Stress and Activation of Redox-Sensitive Kinases in High Fructose- and High-Fat-Fed Male Wistar Rats. Sci Pharm. 2014;83(1):159-175.
30. 30. Naik SR, Thakare VN, Patil SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property. Exp Toxicol Pathol. 2011;63(5):419-431.
31. 31. Hismiogullari AA, Hismiogullari SE, Karaca O, Sunay FB, Paksoy S, Can M, Yavuz O. The protective effect of curcumin administration on carbon tetrachloride (CCl 4)-induced nephrotoxicity in rats. Pharmacological Reports. 2015:67(3);410-416.
32. 32. Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Sripradha R, Badhe B. Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats. Pharm Biol. 2016;54(12):2857-2863.
33. 33. Wu J, Li Q, Wang X, Yu S, Li L, Wu X, Chen Y, Zhao J, Zhao Y. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway. PLoS One. 2013;8(3):e59843.
34. 34. Li Y, Li J, Li S, Li Y, Wang X, Liu B, Fu Q, Ma S. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicol Appl Pharmacol. 2015;286(1):53-63.
35. 35. Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019;129(10):3990-4000.
36. 36. Alipourfard I, Datukishvili N, Mikeladze D. TNF-α Downregulation Modifies Insulin Receptor Substrate 1 (IRS-1) in Metabolic Signaling of Diabetic Insulin-Resistant Hepatocytes. Mediators Inflamm. 2019;2019:3560819.