Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes

Wang,Yong‑Bin; Ge,Zhi‑Ming; Kang,Wei‑Qiang; Lian,Zhe‑Xun; Yao,Jian; Zhou,Chang‑Yong

doi:10.3892/etm.2014.2090

Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes

Authors:
- Yong‑Bin Wang
- Zhi‑Ming Ge
- Wei‑Qiang Kang
- Zhe‑Xun Lian
- Jian Yao
- Chang‑Yong Zhou
View Affiliations

Affiliations: Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, P.R. China, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China, Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: November 26, 2014 https://doi.org/10.3892/etm.2014.2090
Pages: 451-455

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin‑induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin.

View Figures

View References

1	Acar E, Ural D, Bildirici U, Sahin T and Yılmaz I: Diabetic cardiomyopathy. Anadolu Kardiyol Derg. 11:732–737. 2011.PubMed/NCBI
2	Battiprolu PK, Gillette TG, Wang ZV, Lavandero S and Hill JA: Diabetic cardiomyopathy: Mechanisms and therapeutic targets. Drug Discov Today Dis Mech. 7:e135–e143. 2010. View Article : Google Scholar
3	West KM, Ahuja MM, Bennett PH, et al: The role of circulating glucose and triglyceride concentrations and their interactions with other ‘risk factors’ as determinants of arterial disease in nine diabetic population samples from the WHO multinational study. Diabetes Care. 6:361–369. 1983. View Article : Google Scholar : PubMed/NCBI
4	Baynes JW: Role of oxidative stress in development of complications in diabetes. Diabetes. 40:405–412. 1991. View Article : Google Scholar : PubMed/NCBI
5	Coppey LJ, Gellett JS, Davidson EP, et al: Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes. 50:1927–1937. 2001. View Article : Google Scholar : PubMed/NCBI
6	Guha M, Bai W, Nadler JL and Natarajan R: Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem. 275:17728–17739. 2000. View Article : Google Scholar : PubMed/NCBI
7	Lin Y, Rajala MW, Berger JP, et al: Hyperglycemia-induced production of acute phase reactants in adipose tissue. J Biol Chem. 276:42077–42083. 2001. View Article : Google Scholar : PubMed/NCBI
8	Aronson D, Bartha P, Zinder O, et al: Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes Relat Metab Disord. 28:674–679. 2004. View Article : Google Scholar : PubMed/NCBI
9	Kreft S, Knapp M and Kreft I: Extraction of rutin from buckwheat (Fagopyrum esculentum Moench) seeds and determination by capillary electrophoresis. J Agric Food Chem. 47:4649–4652. 1999. View Article : Google Scholar : PubMed/NCBI
10	Huang WY, Zhang HC, Liu WX and Li CY: Survey of antioxidant capacity and phenolic composition of blueberry, blackberry, and strawberry in Nanjing. J Zhejiang Univ Sci B. 13:94–102. 2012. View Article : Google Scholar : PubMed/NCBI
11	Potter JD: Cancer prevention: epidemiology and experiment. Cancer Lett. 114:7–9. 1997. View Article : Google Scholar : PubMed/NCBI
12	Rice-Evans C and Packer L: Flavonoids in Health and Diseases. 13. Marcel Decker; New York, NY: pp. 483–522. 1998
13	Deschner EE, Ruperto J, Wong G and Newmark HL: Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 12:1193–1196. 1991. View Article : Google Scholar : PubMed/NCBI
14	Aleksandrov PN, Speranskaia TV, Bobkov IuG, Zagorevskiĭ VA and Zykov DA: Effect of rutin and esculamine on models of aseptic inflammation. Farmakol Toksikol. 49:84–86. 1986.(In Russian). PubMed/NCBI
15	Pozin VM, Skuratovskaia SG and Pocheptsova GA: Changes in the vascular wall and ischemic damages to the myocardium in reversible episodes of heart muscle ischemia. Fiziol Zh. 42:10–16. 1996.(In Russian).
16	Janbaz KH, Saeed SA and Gilani AH: Protective effect of rutin on paracetamol- and CCl₄-induced hepatotoxicity in rodents. Fitoterapia. 73:557–563. 2002. View Article : Google Scholar : PubMed/NCBI
17	Nagasawa T, Tabata N, Ito Y, et al: Dietary G-rutin suppresses glycation in tissue proteins of streptozotocin-induced diabetic rats. Mol Cell Biochem. 252:141–147. 2003. View Article : Google Scholar : PubMed/NCBI
18	Nagasawa T, Tabata N, Ito Y, et al: Inhibition of glycation reaction in tissue protein incubations by water soluble rutin derivative. Mol Cell Biochem. 249:3–10. 2003. View Article : Google Scholar : PubMed/NCBI
19	Szkudelski T: The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 50:537–546. 2001.
20	Kamalakkannan N and Prince PS: Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocininduced diabetic wistar rats. Basic Clin Pharmacol Toxicol. 98:97–103. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wang HJ, Jin YX, Shen W, et al: Low dose streptozotocin (STZ) combined with high energy intake can effectively induce type 2 diabetes through altering the related gene expression. Asia Pac J Clin Nutr. 16(Suppl 1): 412–417. 2007.PubMed/NCBI
22	Ti Y, Xie GL, Wang ZH, et al: TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model. Diabetes. 60:2963–2974. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tarquini R, Lazzeri C, Pala L, Rotella CM and Gensini GF: The diabetic cardiomyopathy. Acta Diabetol. 48:173–181. 2011. View Article : Google Scholar
24	Yu W, Wu J, Cai F, et al: Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLosOne. 7:e520132012. View Article : Google Scholar
25	Boudina S and Abel ED: Diabetic cardiomyopathy revisited. Circulation. 115:3213–3223. 2007. View Article : Google Scholar : PubMed/NCBI
26	Rajesh M, Mukhopadhyay P, Bátkai S, et al: Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 56:2115–2125. 2010. View Article : Google Scholar : PubMed/NCBI
27	Wang J, Wang H, Hao P, et al: Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats. Mol Med. 17:172–179. 2011.
28	Frantz S, Brandes RP, Hu K, et al: Left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91PHOX. Basic Res Cardiol. 101:127–132. 2006. View Article : Google Scholar
29	Mano Y, Anzai T, Kaneko H, et al: Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy. Circ J. 75:1717–1727. 2011. View Article : Google Scholar : PubMed/NCBI
30	Cuzzocrea S, Riley DP, Caputi AP and Salvemini D: Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 53:135–159. 2011.