Metabolik sendromlu sıçanların karaciğerlerinde oksidatif strese karşı kuersetinin olası koruyucu etkisi

Amaç: Metabolik sendrom (MS), yüksek şeker düzeyi ve insülin direnci ile ilişkilendirilen tip 2 diyabetin tipine bağlıdır. Tiyoredoksin-1 (TRX-1) sitoplazma ve mitokondride yerleşmiştir ve hücresel reaktif oksijen türlerini kontrol eder. Bu çalışmanın amacı, MS sıçanların karaciğerinde, MS ve oksidatif stres arasındaki ilişkiyi ve kuersetinin TRX-1 bağlantılı oksidatif stres üzerindeki etkisini araştırmaktır. Gereç ve Yöntem: Erkek Wistar sıçanlar (200-250g ağırlığında) kullanıldı. Üç gruba ayrıldılar. Kontrol grup, MS grup (935 mM sükroz içeren içme suyu) ve kuersetin uygulanmış (15 mg/kg/gün, gavaj ile) MS grup. TRX-1 protein seviyesi Western blot ile belirlenmiştir.Bulgular: MS gruptaki aspartat transaminaz (AST), alanin transaminaz (ALT), laktat dehidrojenaz (LDH) seviyeleri Kon grubu ile karşılaştırıldığında arttı. MS grubundaki toplam-antioksidan-durumu (TAS), süperoksit-dizmutaz (SOD), ve glutatyon-peroksidaz (GSH-Px) seviyeleri Kon grubu ile karşılaştırıldığında azaldı. MS grubundaki toplam-oksidan-durumu (TOS) seviyesi Kon grubu ile karşılaştırıldığında azaldı. MS grubundaki trigliserit, toplam-kolesterol ve LDL-kolesterol Kon grubu ile karşılaştırıldığında arttı. MS grubundaki TRX-1 seviyesi Kon grubu ile karşılaştırıldığında azalırken TRX-1 aktivitesi ise düştü. Sonuç: Kuersetin tedavisi AST, ALT, LDH, ve TOS seviyelerini azaltırken GSH-Px, SOD, ve TAS seviyelerini artırdı. Ayrıca, yağ profili de kuersetin ile değişti. Sonuç olarak, Kuersetin tedavisi, MS grubundaki TRX-1 seviyesini ve aktivitesini önemli derecede artırdı. Bu veriler MS karaciğerinde artmış olan oksidatif stresin kuersetin ile azalabildiğini ileri sürmektedir.

Anahtar Kelimeler:

Metabolik sendrom, kuersetin, oksidatif stres, insülin direnci, karaciğer

Possible protective effect of quercetin against oxidative stress in liver from metabolic syndrome rats

AbstractBackground/Aims:Metabolic syndrome (MS) is linked to type of type 2 diabetes mellitus associated with high glucose level and insulin resistance. Thioredoxin-1 (TRX-1) is localized in the cytoplasm and the mitochondria and controls cellular reactive oxygen species. The purpose of this study is to examine the relation between MS and oxidative stress, and effect of quercetin on oxidative stress via TRX-1 in liver of MS rats. Methods: Male wistar rats (200-250g in weight) were used. They were divided three groups. Control group, MS group receiving (935 mM sucrose in drinking water) and quercetin treated (15 mg/kg/day, administered by gavage) MS group. Protein level of TRX-1 was determined by Western blot.Results:Aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), levels increased in MS group as compared with the Con group. Total-antioxidant-status (TAS), superoxide-dismutase (SOD), and glutathione-peroxidase (GSH-Px) levels decreased in MS group when compared to Con group. Total-oxidant-status (TOS) levels increased in MS group as compared with the Con group. Triglycerides, total-cholesterol and LDL-cholesterol increased in MS group when compared with the Con group. TRX-1 level decreased in MS group and TRX-1 activity was lower in MS group than Con group. Conclusions: Treatment of quercetin decreased AST, ALT, LDH, and TOS levels while it increased GSH-Px, SOD, and TAS levels. Also, lipid profile changed with quercetin. In conclusion, treatment of quercetin significantly increased TRX-1 level and activity of TRX-1 in MS group. These data suggest that elevated oxidative stress in liver of MS may be reduced by quercetin.

Keywords:

Metabolic syndrome, quercetin, oxidative stress, insulin resistance, liver,

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1. Ando K, Fujita T. Metabolic syndrome and oxidative stress. Free Radic Biol Med 2009;47:213–18.
2. Vincent HK, Taylor AG. Biomarkers and potential mechanisms of obesity induced oxidant stress in humans. Int J Obes 2006;30:400–18.
3. Sies H. Oxidative stress: Oxidants and antioxidants London: San Diego; 1991.
4. Cabre M, Comps J, Paternain JL et al. Time course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon tetrachloride-induced cirrhosis. Clin Exp Pharmacol Physiol 2000;27:694-9.
5. Vincent A.M, Russell JW, Low P et al. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocrine Reviews 2004;25:612-28.
6. Altan N, Dinçel AS, Koca C. Diabetes mellitus and oxidative stress. Turkish J Biochem 2006;31: 51-6.
7. Lonardo A, Ballestri S, Marchesinin G et al. Nonalcoholic fatty liver disease: A precursor of the metabolic syndrome. Dig Liver Dis 2015;47:181-90.
8. Lonardo A, Nascimbeni F, Mantovani A et al. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? J Hepatol 2018;68:335-52.
9. Aguirre L, Arias N, Macarulla MT et al. Beneficial effects of quercetin on obesity and diabetes. The Open Nutraceuticals J 2011;4:189-98.
10. Saija A, Scalese M, Lanza M et al. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med 1995;19:481–6.
11. Kim HP, Mani I, Ziboh VA. Effects of naturally-occurring flavonoids and bio-flavonoids on epidermal cyclooxygenase from guinea-pigs. Prostaglandins Leukot Essent Fatty Acids 1998;58:17–24.
12. Arne´r ES, Holmgren A. The thioredoxin system in cancer. Semin Cancer Biol 2006;16:420–6.
13. Collet JF, Messens J. Structure, function, and mechanism of thioredoxin proteins. Antioxid Redox Signal. 2010;13:1205–16.
14. Yamawaki H, Berk BC. Thioredoxin: a multifunctional antioxidant enzyme in kidney, heart and vessels. Curr Opin Nephrol Hypertens 2005;14:149–53.
15. Ballestri S, Nascimbeni F, Baldelli E et al. NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk. Adv Ther 2017;34:1291-326.
16. Ruiz-Ramirez A, Chavez-Salgado M, Peneda-Flores JA et al. High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria. Am J Physiol Endocrinol Metab 2011;301:E1198-207.
17. Matthews DR, Hosker JP, Rudenski AS et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.
18. Vasques AC, Rosado LE, Cassia GR et al. Critical analysis on the use of the homeostasis model assessment (HOMA) indexes in the evaluation of the insulin resistance and the pancreatic beta cells functional capacity. Arq Bras Endocrinol Metabol 2008;52:32-9.
19. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497-500.
20. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70:158-69.
21. Kim SH, Sung KC, Reaven GM. Utility of Homeostasis Model Assessment of β-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans. Diabetes Care 2010;33: e72.
22. Delbosc S, Paizanis E, Magous R et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 2005;179:43–9.
23. Pompella A, Visvikis A, Paolicchi A et al. The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 2003;66:1499–503.
24. Somade OT, Akinloye OA, Adeyeye MO et al. Quercetin, a natural phytochemical and antioxidant protects against sodium azide-induced hepatic and splenic oxidative stress in rats. A J Physiol Biochem Pharmacol 2015;4: 69-74.
25. Sonmez E, Cacciatore I, Bakan F et al. Toxicity assessment of hydroxyapatite nanoparticles in rat liver cell model in vitro Human and Experimental Toxicology 2016;35:1–11.
26. Alam M, Meerza D, Naseem I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sciences 2014;109:8–14.
27. Serafini M, DelRio D. Understanding the association between dietary antioxidants, redox status and disease: is the Total Antioxidant Capacity the right tool? Redox Rep 2004;9:145-52.
28. Mazloom Z, Abdollahzadeh SM, Dabbaghmanesh MH et al. The Effect of Quercetin Supplementation on Oxidative Stress, Glycemic Control, Lipid Profile and Insulin Resistance in Type 2 Diabetes: A Randomized Clinical Trial. J Health Sci Surveillance Sys January 2014;Vol 2; No 1
29. Sahebkar, A. Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2017;57:666–76.
30. Miyamoto S, Kawano H, Hokamaki J et al. Increased plasma levels of thioredoxin in patients with glucose intolerance. Intern Med 2005;44:1127–32.
31. Okuyama H, Nakamura H, Shimahara Y et al. Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice. Hepatology 2003;37:1015–25.
32. Kakisaka Y, Nakashima T, Sumida Y et al. Elevation of serum thioredoxin levels in patients with type 2 diabetes. Hom Metab Res 2002;34:160–4.