Official journal of the Slovak Society of Cardiology,
Slovak Society of Hypertension and Slovak Association for Cardiac Arrhythmias

Cardiology Letters 2015, 24(4):243-246

Pathological changes in cardiovascular system in long-term doxorubicin-treated rats and effect of quercetin

Dovinová I1, Barančík M2, Krátka D3, Fogarassyová M2, Kvandová M1, Barteková M2
1 Ústav normálnej a patologickej fyziológie, Slovenská akadémia vied, Bratislava
2 Ústav pre výskum srdca, Slovenská akadémia vied, Bratislava
3 Ústav patologickej fyziológie, Lekárska fakulta UK, Bratislava, Slovenská republika

Aims: Doxorubicin is an effective anticancer drug, but with several limitations in treatment. Application of anthracycline - doxorubicin (DOX) induces chronic pathological changes in the myocardium. The mechanisms of DOX cardiotoxicity may be multifactorial, including increased production of reactive oxygen species leading to oxidative stress, cell necrosis and apoptosis induction. Treatment with additional substances such as flavonoids can influence the negative effect of doxorubicin, and quercetin (QCT) was found as a potential preventive substance in the treatment of cardiovascular diseases. The aim of the present study was to determine the effect of QCT administration in long-term doxorubicine treated Wistar rats.

Methods: In the study, 11-weeks old male Wistar rats were divided into control group, saline-treated and experimental groups. Experimental groups of animal were treated either with cumulative doses of doxorubicin (DOX, 15 mg/kg, 3 weeks, i.p.) or with combination of doxorubicin+quercetin (DOX-QCT, each for 3 weeks, QCT, 20 mg/kg, in biscuit pieces). Blood pressure was detemined using the plethysmography method. Eight weeks after the completion of DOX, DOX-QCT or saline treated samples from the left ventricle were collected for further biochemical studies: Western blot analysis and enzyme activity measurements.

Results: DOX influenced blood pressure increase, while a combination of QCT + DOX lowered blood pressure increase and stabilised its to the control values. The effect of DOX on MMP-2 activities and improvement of SOD activities and mitochondrial SOD protein expression to control level was affected by QCT administration.

Conclusion: Quercetin administration was effective in blood pressure normalisation as well as in backward remodelation and improvement of antioxidant response in the left ventricle of long-term DOX-treated animals.

Keywords: blood pressure; heart failure; matrix metalloproteinase-2; antioxidant response and mitochondrial SOD; doxorubicin; quercetin

Published: April 1, 2015  Show citation

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Dovinová I, Barančík M, Krátka D, Fogarassyová M, Kvandová M, Barteková M. Pathological changes in cardiovascular system in long-term doxorubicin-treated rats and effect of quercetin. Cardiology Letters. 2015;24(4):243-246.
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References

  1. Barnes S, Prasain J, D'Alessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle EM, Weaver CM (2011). The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food & Function 2(5):235. Go to original source...
  2. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;582(23):325-337. Go to original source...
  3. Sanchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, PérezVizcaíno F, Duarte J. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J. Hypertension 2006;24:75-84. Go to original source...
  4. Yamamoto Y, Oue E. Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci. Biotechnol. Biochem. 2006;70:933-939. Go to original source...
  5. Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. 2007;137(11):2405-2411. Go to original source...
  6. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004;56:185-229. Go to original source...
  7. Perego P, Corna E, De Cesare M, Gatti L, Polizzi D, Pratesi G, Supino R, Zunino F. Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficiacy of anthracyclines. Curr Med Chem. 2001 Jan;8(1):31-37. Go to original source...
  8. Ivanova M, Dovinova I, Okruhlicova L, Tribulova N, Simoncikova P, Bartekova M, Vlkovicova J, Barancik M. Chronic cardiotox­ icity of doxorubicin involves activation of myocardial and circulating matrix metalloproteinases in rats. Acta Pharmacol. Sin. 2012;33:459-469. Go to original source...
  9. Stěrba M, Popelová O, Vávrová A, Jirkovský E, Kovaříková P, Geršl V, Simůnek T.Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection. Antioxid Redox Signal. 2013;18(8):899929. Go to original source...
  10. Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res. 2000;60:1789-1792.
  11. Barteková M, Šimončíková P, Fogarassyová M, Ivanová M, Okruhlicová Ľ, Tribulová N, Dovinová I, Barančík M. Quercetin improves postischemic recovery of heart function in doxorubicin-treated rats and prevents doxorubicin-induced matrix metalloproteinase-2 activation and apoptosis induction. Int. J. Mol. Sci. 2015;16:2015. Go to original source...