Effect of Resveratrol on Proinflammatory Gene Expression in Pancreas of Streptozotocin Induced Diabetic Rats

  • Buket Yurteri Gazi University
  • Emine Sevda Menevşe Gazi University
  • Atiye Seda Yar Sağlam Gazi University
Keywords: Diabetes Mellitus, Streptozotocin, Resveratrol, Real-time PCR


Objective: Inflammation and oxidative stress play an important role in the development of Diabetes mellitus (DM). The production amount of increased reactive oxygen types in ß-cells that are sensitive to oxidative stress cause degeneration in insulin release and insulin resistance in Type 2 DM. Streptozotocin(STZ) breaks down ß-cells with the accumulation of free radicals by inhibiting pancreas superoxide dismutase. And Resveratrol (RSV) has an inhibitory effect on the degenaration of pancreatic ß cells. In this study, we aimed to examine the impact of expressions in NF-κB, TNFα, IL-6, iNOS and COX2 genes in STZ-induced diabetes in pancreases of rats on the complications of DM. Methods: STZ-induced diabetes in pancreases of rats and RSV applied pancreatic tissues of rats after inducing diabetes are used. RNA isolation and cDNA synthesis are conducted for these tissues. mRNA expressions of NF-κB, TNFα, IL-6, iNOS and COX2 genes are realized with real-time PCR reaction and results are evaluated statistically. Results: No significant difference is observed between control, sham control and control+DMSO groups on COX2, iNOS, NF-κB, TNFα and IL-6 in mRNA level. When control and diabetes groups are compared, it is observed that mRNA levels of COX2, iNOS, NF-κB, TNFα and IL-6 genes increased in mRNA expression levels of target genes in diabetes group. This presents a statistical meaning between two groups. And when diabetes and diabetes+RSV groups are compared, decrease in COX2, iNOS, NF-κB, TNFα and IL-6 genes are observed in mRNA levels. It is observed that this decrease is not statistically meaningful. Conclusion: Data obtained shows that there is decrease in expression levels of inflammatory genes in diabetic rats and RSV application has no statistically significant effect on expression levels of these genes. From this point of view it can be said that only RSV application cannot change the expression levels of inflammatory genes associated with diabetes.

Author Biographies

Buket Yurteri, Gazi University
Faculty of Medicine, Department of Medical Biology and Genetics and MSc
Emine Sevda Menevşe, Gazi University
Faculty of Medicine, Department of Medical Biology and Genetics and Prof.Dr.
Atiye Seda Yar Sağlam, Gazi University
Faculty of Medicine, Department of Medical Biology and Genetics and Assoc.Prof.


Robertson RP, Harmon JS. Diabetes, glucose toxicity, and oxidative stress: A case of double jeopardy for the pancreatic islet beta cell. Free Radic Biol Med, 2006; 41(2):177-84.

Dinççağ N. Diabetes Mellitus Tanı ve Tedavisinde Güncel Durum. İç Hastalıkları Dergisi, 2011;18(4):181- 223.

Canda M. Temel Patoloji, İstanbul: Nobel Yayınları, 1994.

American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2004;27(1):5-S10.

Aruzmozhi D, Veeranjaneyulu A, Bodhankar S. Neonatal streptozotocin- ınduced rat model of type 2 diabetes mellitus: a glance. Indian J. Pharmacology, 2004;36(4):217-221

Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-46.

Martinez J, Moreno J. Effect of Resveratrol, A Natural Polphenolic Compound, On Reactive Oxygen Species and Prostaglandin Production. Biochem Pharmacol. 2000;59(7):865-70.

Gehm B, McAndrews J, Chien P, Jameson J. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A. 1997; 94(25): 14138–14143.

Pfaffl M. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45.

Yar A.S. Streptozotozin ile oluşturulmuş diyabetli sıçanlarda resveratrol kullanımı sonucunda siklooksijenaz-1 (COX-1) ve siklooksijenaz-2 (COX-2) genlerinin ekspresyonlarının araştırılması, Yüksek Lisans Tez Çalışması, 2008.

Satman I, Ömer B, Tütüncü Y, Kalaca S, Gedik S, Dinççağ N. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013 Feb;28(2):169-80.

Saha S, Ghosh M. Antioxidant and anti-inflammatory effect of conjugated linolenic acid isomers against streptozotocin-induced diabetes. Br J Nutr. 2012;108(6):974-83.

Lekshmi R, Raiesh R, Mini S. Ethyl acetate fraction of Cissus quadrangularis stem ameliorates hyperglycaemia-mediated oxidative stress and suppresses inflammatory response in nicotinamide/streptozotocin induced type 2 diabetic rats. Phytomedicine. 2015;22(10):952-60.

Akcılar R, Kocak F, Simsek H, Akcılar A, Bayat Z, Ece E, Kokdasgil H. Antidiabetic and hypolipidemic effects of adropinin streoptozotocin-induced type 2 diabetic rats. Bratisl Lek Listy. 2016;117(2):100-5.

He J, Yang Z, Yang H, Wang L, Wu H, Fan Y, Wang W, Fan X, Li X. Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus. Peptides. 2015;64:49-54.

Williams L, Burdock G, Edwards J, Beck M, Bausch J. Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food Chem Toxicol. 2009;47(9):2170-82.

Horn TL, Cwik MJ, Morrissey RL, Kapetanovic I, Crowell JA, Booth TD, McCormick DL. Oncogenicity evaluation of resveratrol in p53(+/-) (p53 knockout) mice. Food Chem Toxicol. 2007;45(1):55-63.

Juan ME, Vinardell MP, Planas JM. The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J Nutr. 2002;132(2):257-60.

Lai X, Pei Q, Song X, Zhou X, Yin Z, Jia R, Zou Y, Li L, Yue G, Liang X, Yin L, Lv C, Jing B. The enhancement of immune function and activation of NF -kB by resveratrol-treatment in immunosuppressive mice. Int Immunopharmacol. 2016;33:42-7.

Crofford L. COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol Suppl. 1997;49:15-9.

Yar AS, Menevse S, Alp E, Helvacioglu F, Take G. The effects of resveratrol on COX-1 and COX- 2 mRNA and protein levels in diabetic rat kidneys. Mol Biol Rep. 2010;37(5):2323-31.

Newton R, Kuitert LM, Bergmann M, Adcock IM, Barnes PJ. Evidence for Involvement of NF -kB in the Transcriptional Control of COX-2 Gene Expression by IL-1β. Biochem Biophys Res Commun. 1997;237(1):28-32.

Zamora R , Vodovotz Y, Billiar T. Inducible nitric oxide synthase and inflammatory diseases. Mol Med. 2000;6(5): 347–373.

Bertelli AA, Baccalini R, Battaglia E, Falchi M, Ferrero ME. Resveratrol inhibits TNF alpha-induced endothelial cell activation. Therapie. 2001;56(5):613-6.

Csiszar A, Smith K, Labinskyy N, Orosz Z, Rivera A, Ungvari Z. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am J Physiol Heart Circ Physiol. 2006;291(4):H1694-9.

Zhong M, Cheng GF, Wang WJ, Guo Y, Zhu XY, Zhang JT. Inhibitory effect of resveratrol on interleukin 6 release by stimulated peritoneal macrophages of mice. Phytomedicine. 1999;6(2):79-84.

Gao Y, Kang L, Li C, Wang X, Sun C, Li Q, Liu R, Wang J. Resveratrol Ameliorates Diabetes-Induced Cardiac Dysfunction Through AT1R-ERK/p38 MAPK Signaling Pathway. Cardiovasc Toxicol. 2016;16(2):130-7

Zheng X, Zhu S, Chang S, Cao Y, Dong J, Li J, Long R, Zhou Y. Protective effects of chronic resveratrol treatment on vascular inflammatory injury in streptozotocin-induced type 2 diabetic rats: Role of NF-kappa B signaling. Eur J Pharmacol. 2013;720:147–57.

Kumar A, Sharma S. NF-kappaB inhibitory action of resveratrol: a probable mechanism of neuroprotection in experimental diabetic neuropathy. Biochem Biophys Res Commun. 2010;394:360–5.

Original Research