Pioglitazon Sıçanlarda Yüksek Sükrozla Başlatılmış Metabolik Sendromda Böbrekteki Oksidatif Stresi Azaltır

Yıl 2018, Cilt: 8 Sayı: 3, 165 - 171, 01.12.2018

Ayça Bilginoğlu Kara

Öz

Amaç: Metabolik
sendrom (MS), kronik böbrek hastalığının ilerlemesinde önemli bir risk
faktörüdür. Tiyazolidindionlar (TZDs) muhtemelen MS’de renovasküler koruma
sağlar. Bununla birlikte, yüksek sükroz başlangıçlı MS’de pioglitazonun böbreğe
ait oksidatif stres üzerine etkisinin açıklanmasıyla ilgili çalışmalar devam
etmektedir. Bu çalışmanın amacı pioglitazonun MS’li sıçanların böbreklerindeki
oksidatif stres belirleyicileri üzerine etkisinin incelenmesidir.

Materyal ve Metot: Çalışmada erkek Wistar türü sıçanlar (200-250 g
ağırlıkta) kullanıldı. Onlar kontrol grup, MS grup (935 mM sükroz içme sularına
katılarak) ve pioglitazon uygulanmış MS grup (MSP); MS grubun 18. haftasından
başlayarak 2 hafta pioglitazon (30 mg/kg/gün, gavajla) uygulandı. Aspartate
amino transferaz (AST), laktat dehidrojenaz (LDH), toplam oksidan durum (TOS),
toplam antioksidan durum (TAS) seviyeleri ticari kitler kullanılarak ölçüldü. Tiyobarbitürik asit
reaktif maddeler  (TBARS), indirgenmiş
glutatyon (GSH), üre, ürik asit and kreatin ölçüldü. Tiyoredoksin 1 (TRX1) düzeyi
sitoplazma ve hücre zarında western blot ile ölçüldü. TRX1 aktivitesi sitoplazma ve
hücre zarında ticari kit kullanılarak öçüldü.

Bulgular: Kontrol sıçanları ile karşılaştırıldığında, sükroz ile
beslenmiş olan sıçanlar abdominal obezite, insulin direnci, hiperinsülinemi, ve
hipertrigliseridemi içeren MS’nin bir çok özelliğini göstermiştir. Bunun
yanında, MS’de değişmiş olan AST, LDH, TOS, TAS, TBARS, GSH, üre, ürik asit and
kreatin, TRX1 aktivitesi ve protein düzeyleri pioglitazon uygulamasıyla kontrol
seviyelerine dönmüştür.

Sonuç: Pioglitazon, MS’li sıçanların böbreklerinde artmış olan
oksidatif stresi azaltmıştır. 

Anahtar Kelimeler

Böbrek, metabolik sendrom, oksidatif stres, pioglitazon

Pioglitazone Reduces Oxidative Stress in Kidney Against High Sucrose Diet-Induced Metabolic Syndrome in Rats

Öz

Aim: The metabolic syndrome
(MS) is an important risk factor for the development of chronic kidney disease.
Thiazolidinediones (TZDs) provide renovascular protection, probably in the MS.
However, reports about the effect of pioglitazone on renal oxidative stress in
high sucrose diet-induced MS remains to be determined. The aim of this study
was to assess the effects of pioglitazone on oxidative stress markers in kidney
tissues of MS rats.

Material
and Method:
Male Wistar rats (200-250g in weight) were used in present study. They were
divided as control (Con) group, MS group (receiving 935 mM sucrose in drinking
water) and pioglitazone treated MS group (MSP) received pioglitazone treatment
(30 mg/kg/day, via gavage) for two weeks at the end of the 18^th
weeks of MS group. Aspartate aminotransferase (AST), lactate dehydrogenase
(LDH), total oxidant status (TOS), and total antioxidant status (TAS) levels
were measured using commercial kits. Thiobarbituric acid reactive substances
(TBARS), reduced glutathione (GSH), urea, uric acid and
creatinine were measured. Thioredoxin 1 (TRX1) level was measured in cytosol
and membrane tissues by western blot. TRX1 activity was measured in cytosol and
membrane tissues using commercial kit.

Results: Compared with control
rats, the sucrose-fed rats exhibited several characteristics of MS, including
central obesity, insulin resistance, hyperinsulinemia, and
hypertriglyceridemia. Furthermore, changed levels of AST, LDH, TOS, TAS, TBARS,
GSH, urea, uric acid, creatinine and TRX1 activity and protein levels in the MS
group were reversed to control levels by administration of pioglitazone.

Conclusion: Pioglitazone reduced
the elevated oxidative stress in kidney of MS rats.

Anahtar Kelimeler

Kidney, metabolic syndrome, oxidative stress, pioglitazone

Kaynakça

• 1. Masson W, Epstein T, Huerín M, Lobo LM, Molinero G, Angel A et al. Cardiovascular risk stratification in patients with metabolic syndrome Without diabetes or cardiovascular disease: Usefulness of metabolic syndrome severity score. High Blood Press Cardiovasc Prev. 2017; 24(3):297-303.
• 2. Huh JH, Yadav D, Kim JS, Son JW, Choi E, Kim SH et al. An association of metabolic syndrome and chronic kidney disease from a 10-year prospective cohort study. Metabolism 2017; 67:54–61.
• 3. Panwar B, Hanks LJ, Tanner RM, Muntner P, Kramer H, McClellan WM et al. Obesity, metabolic health, and the risk of end-stage renal disease. Kidney Int 2015; 87:1216–22.
• 4. Prasad GVR. Metabolic syndrome and chronic kidney disease: current status and future directions. World J Nephrol 2014; 3:210–9.
• 5. Kurella M, Lo JC, Chertow GM. Metabolic syndrome andthe risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol. 2005; 16:2134–40.
• 6. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240:889-95.
• 7. Peraldi P, Xu M, Spiegelman BM. Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling. J Clinl Invest. 1997; 100:1863.
• 8. Hallakou S, Doare L, Foufelle F, Kergoat M, Guerre-Millo M, Berthault MF et al. Pioglitazone induces in vivo adipocyte differentiation in the obese zucker fa/fa rat. Diabetes 1997; 46:1393-9.
• 9. Qi HP, Wang Y, Zhang QH, Guo J, Li L, Cao YG et al. Activation of peroxisome proliferator-activated receptor γ (PPARγ) through NF-κB/BRG1 and TGF-β1 pathways attenuates cardiac remodeling in pressure-overloaded rat hearts. Cell Physiol Biochem 2015; 35:899-912.
• 10. Zou C, Hu H, Xi X, Shi Z, Wang G, Huang X. Pioglitazone protects against renal ischemia-reperfusion injury by enhancing antioxidant capacity. J Surg Res. 2013; 184:1092-5.
• 11. Keaney Jr JF, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003; 23:434–9.
• 12. Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK et al. A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress. PLoS One 6 2011; e24028.
• 13. Ruiz-Ramirez A, Chavez-Salgado M, Peneda-Flores JA, Zapata E, Masso F, El-Hafidi M. 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.
• 14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28:412-9.
• 15. Vasques AC, Rosado LE, Cassia GR, Geloneze B: 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.
• 16. Wasowicz W, Nève J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem 1993; 39:2522-6.
• 17. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82(1):70–7.
• 18. Hammes, S. R. The further redefining of steroid-mediated signaling. Proc Natl Acad Sci 2003; 100(5): 21680–700.
• 19. Agbafor. K. N., Engwa. A. G., Ude. C. M., Obiudu. I. K. and Festus. B. O. Effect of Aqueous Leave Extract of Ageratum Conyzoides on Blood Glucose, Creatinine and Calcium ion Levels in Albino rats. Journal of pharmaceutical Chemical and Biological Sciences 2015; 3(3): 408-15.
• 20. Barham, T. Enzymatic Colorimetric Determination of Uric Acid. Journal of Clinical Chemistry 1972; 97(2): 142 -4.
• 21. Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004; 140:167–74.
• 22. Soria A, D’Alessandro ME, Lombardo YB. Duration of feeding on a sucrose-rich diet determines metabolic and morphological changes in rat adipocytes. J Appl Physiol 2001;91:2109-16.
• 23. Adedara IA, Abolaji AO, Odion BE, Okwudi IJ, Omoloja AA, Farombi EO. Impairment of hepatic and renal functions by 2,5-hexanedione is accompanied by oxidative stress in rats. J Toxicol 2014; 2014:239240.
• 24. Suanarunsawat T, Ayutthaya WD, Songsak T, Thirawarapan S, Poungshompoo S Lipid-lowering and antioxidative activities of aqueous extracts of Ocimum sanctum L. leaves in rats fed with a high-cholesterol diet. Oxid Med Cell Longev. 2011; 2011: 962025.
• 25. Akila P, Asaikumar L, Vennila L. Chlorogenic acid ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes. Biomed Pharmacother 2017; 85:582-91.
• 26. Quigg RJ, Cybulsky AV, Jacobs JB, Salant DJ. Anti-Fx1A produces complement-dependent cytotoxicity of glomerular epithelial cells. Kidney international 1988; 34:43-52.
• 27. Vikramathithan J, Gautami G, Ganesh I, Srikumar K. Differences in Rat Tissue Lactate Dehydrogenase Activity Caused by Giberellic Acid and Homobrassinolide. Türk Biyokimya Dergisi [Turkish Journal of Biochemistry–Turk J Biochem] 2009; 34(2):57–61.
• 28. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med. 2000; 29:1106-14.
• 29. Liu J, Yeo HC, Övervik-Douki E, Hagen T, Doniger SJ, Chyu DW et al. Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol. 2000; 89:21-8.
• 30. Yamawaki H, Haendeler J, Berk BC. Thioredoxin: a key regulator of cardiovascular homeostasis. Circ Res. 2003; 93:1029-33.