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Article

Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction

  • Authors:
    • Mariele Dessì
    • Alessandra Piras
    • Clelia Madeddu
    • Christian Cadeddu
    • Martino Deidda
    • Elena Massa
    • Giorgia Antoni
    • Giovanni Mantovani
    • Giuseppe Mercuro
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, University of Cagliari, 09042 Monserrato (CA), Italy, Department of Cardiovascular and Neurological Sciences, University of Cagliari, 09042 Monserrato (CA), Italy, Cattedra di Oncologia Medica, Università di Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, 09042 Monserrato (CA), Italy
  • Pages: 1003-1009
    |
    Published online on: June 30, 2011
       https://doi.org/10.3892/etm.2011.305
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Abstract

Chronic inflammation, oxidative stress and the renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, was found to reduce anthracycline (ANT)-induced CTX. We carried out a phase II placebo (PLA)-controlled randomized trial to assess the possible role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were determined. All assessments were carried out at baseline, after every 100 mg/m2 of EPI dose and at the 12-month follow-up (FU). A significant reduction in the SR peak both in the TEL and PLA arms was observed at t2 (cumulative dose of 200 mg/m2 of EPI) in comparison to t0. Conversely, at t3 (300 mg/m2 EPI), t4 (400 mg/m2 EPI) and the 12-month FU, the SR increased reaching the normal range only in the TEL arm, while in the PLA arm the SR remained significantly lower as compared to t0 (baseline). The differences between SR changes in the PLA and TEL arms were significant from 300 mg/m2 EPI (t3) up to the 12-month FU. Serum levels of IL-6 increased significantly in the PLA arm at 200 mg/m2 EPI (t2) in comparison to baseline, but remained unchanged in the TEL arm. The same trend was demonstrated for ROS levels which significantly increased at t2 vs. baseline in the PLA arm, while remained unchanged in the TEL arm. The mean change in ROS and IL-6 at t2 was significantly different between the two arms. In the present study, we confirmed at the 3-month FU a trend toward a decrease in ROS and IL-6 from t2 in the PLA arm. Our results suggest that TEL is able to reverse acute (early) EPI-induced myocardial dysfunction and to maintain later a normal systolic function up to the 12-month FU. These effects are likely to be due to different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.
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1. 

Escobar E, Rodriguez-Reyna TS, Arrieta O and Sotelo J: Angiotensin II, cell proliferation and angiogenesis regulator: biologic and therapeutic implications in cancer. Curr Vasc Pharmacol. 2:385–399. 2004. View Article : Google Scholar : PubMed/NCBI

2. 

Thompson KL, Rosenzweig BA, Zhang J, et al: Early alterations in heart gene expression profiles associated with doxorubicin cardiotoxicity in rats. Cancer Chemother Pharmacol. 66:303–314. 2010. View Article : Google Scholar : PubMed/NCBI

3. 

Funao K, Matsuyama M, Kawahito Y, et al: Telmisartan is a potent target for prevention and treatment in human prostate cancer. Oncol Rep. 20:295–300. 2008.PubMed/NCBI

4. 

Paulides M and Wojnowski L: [Chemotherapeutics-induced heart failure]. Med Klin. 102:574–578. 2007.(In German).

5. 

Meldrum DR, Cleveland JC Jr, Cain BS, Meng X and Harken AH: Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Ann Thorac Surg. 65:439–443. 1998. View Article : Google Scholar

6. 

Kupatt C, Habazettl H, Goedecke A, et al: Tumor necrosis factor-alpha contributes to ischemia- and reperfusion-induced endothelial activation in isolated hearts. Circ Res. 84:392–400. 1999. View Article : Google Scholar : PubMed/NCBI

7. 

Mercuro G, Cadeddu C, Piras A, et al: Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 12:1124–1133. 2007. View Article : Google Scholar

8. 

Mantovani G, Madeddu C, Cadeddu C, et al: Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 13:1296–1305. 2008. View Article : Google Scholar

9. 

Toko H, Oka T, Zou Y, et al: Angiotensin II type 1a receptor mediates doxorubicin-induced cardiomyopathy. Hypertens Res. 25:597–603. 2002. View Article : Google Scholar : PubMed/NCBI

10. 

Soga M, Kamal FA, Watanabe K, et al: Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats. Int J Cardiol. 110:378–385. 2006. View Article : Google Scholar : PubMed/NCBI

11. 

Oken MM, Creech RH, Tormey DC, et al: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655. 1982. View Article : Google Scholar : PubMed/NCBI

12. 

Iqbal M, Dubey K, Anwer T, Ashish A and Pillai KK: Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats. Pharmacol Rep. 60:382–390. 2008.PubMed/NCBI

13. 

Ishiguro H, Ishiguro Y, Kubota Y and Uemura H: Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action. Prostate. 67:924–932. 2007. View Article : Google Scholar : PubMed/NCBI

14. 

Cadeddu C, Piras A, Mantovani G, et al: Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment. Am Heart J. 160:e481–e487. 2010. View Article : Google Scholar

15. 

Wenzel P, Schulz E, Oelze M, et al: AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats. Free Radic Biol Med. 45:619–626. 2008. View Article : Google Scholar : PubMed/NCBI

16. 

Stephen RL, Gustafsson MC, Jarvis M, et al: Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Res. 64:3162–3170. 2004. View Article : Google Scholar

17. 

Jensen BV, Skovsgaard T and Nielsen SL: Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 13:699–709. 2002. View Article : Google Scholar : PubMed/NCBI

18. 

Jalowy A, Schulz R and Heusch G: AT1 receptor blockade in experimental myocardial ischemia/reperfusion. Basic Res Cardiol. 93(Suppl 2): 85–91. 1998. View Article : Google Scholar

19. 

Ferreira AL, Matsubara LS and Matsubara BB: Anthracycline-induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem. 6:278–281. 2008. View Article : Google Scholar

20. 

Cianchetti S, del Fiorentino A, Colognato R, di Stefano R, Franzoni F and Pedrinelli R: Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis. 198:22–28. 2008. View Article : Google Scholar : PubMed/NCBI

21. 

Yamagishi S and Takeuchi M: Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. Med Hypotheses. 64:476–478. 2005. View Article : Google Scholar : PubMed/NCBI

22. 

Tuck ML: Angiotensin-receptor blocking agents and the peroxisome proliferator-activated receptor-gamma system. Curr Hypertens Rep. 7:240–243. 2005. View Article : Google Scholar : PubMed/NCBI

23. 

Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI

24. 

Conklin KA: Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 4:110–130. 2005. View Article : Google Scholar : PubMed/NCBI

25. 

Kaur K, Sharma AK, Dhingra S and Singal PK: Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes. J Mol Cell Cardiol. 41:1023–1030. 2006. View Article : Google Scholar : PubMed/NCBI

26. 

Sipahi I, Debanne SM, Rowland DY, Simon DI and Fang JC: Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 11:627–636. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Dessì M, Piras A, Madeddu C, Cadeddu C, Deidda M, Massa E, Antoni G, Mantovani G and Mercuro G: Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction. Exp Ther Med 2: 1003-1009, 2011.
APA
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E. ... Mercuro, G. (2011). Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction. Experimental and Therapeutic Medicine, 2, 1003-1009. https://doi.org/10.3892/etm.2011.305
MLA
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E., Antoni, G., Mantovani, G., Mercuro, G."Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction". Experimental and Therapeutic Medicine 2.5 (2011): 1003-1009.
Chicago
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E., Antoni, G., Mantovani, G., Mercuro, G."Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction". Experimental and Therapeutic Medicine 2, no. 5 (2011): 1003-1009. https://doi.org/10.3892/etm.2011.305
Copy and paste a formatted citation
x
Spandidos Publications style
Dessì M, Piras A, Madeddu C, Cadeddu C, Deidda M, Massa E, Antoni G, Mantovani G and Mercuro G: Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction. Exp Ther Med 2: 1003-1009, 2011.
APA
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E. ... Mercuro, G. (2011). Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction. Experimental and Therapeutic Medicine, 2, 1003-1009. https://doi.org/10.3892/etm.2011.305
MLA
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E., Antoni, G., Mantovani, G., Mercuro, G."Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction". Experimental and Therapeutic Medicine 2.5 (2011): 1003-1009.
Chicago
Dessì, M., Piras, A., Madeddu, C., Cadeddu, C., Deidda, M., Massa, E., Antoni, G., Mantovani, G., Mercuro, G."Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction". Experimental and Therapeutic Medicine 2, no. 5 (2011): 1003-1009. https://doi.org/10.3892/etm.2011.305
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