Effect of telmisartan in limiting the cardiotoxic effect of daunorubicin in rats

Wawaimuli Arozal, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Rajarajan A. Thandavarayan, Meilei Harima, Vijayakumar Sukumaran, Kenji Suzuki, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Objectives Studies have suggested that angiotensin receptor blockers may exert a protective role towards doxorubicin-induced cardiotoxicity, but they have not been extensively investigated in this area. We therefore investigated whether the co-treatment of telmisartan, an angiotensin (Ang II) type-1 receptor blocker, might offer protection against daunorubicin cardiotoxic properties in rats. Methods Daunorubicin was administered at 3mg/kg/day every other day for 12 days. Telmisartan was administered orally every day for 12 days. Key findings Daunorubicin-treated rats showed cardiac toxicity, evidenced by worsening cardiac function, evaluated by haemodynamic status and echocardiography, elevation of malondialdehyde level and a decreased level of total glutathione peroxidase activity in the heart tissue. These changes were reversed by treatment with telmisartan. Furthermore, telmisartan also downregulated matrix metalloproteinase-2 expression, attenuated the increased protein expression of p22phox, p47phox, p67phox, nuclear factor kappa B and Nox4 in heart tissue, and reduced oxidative-stress-induced DNA damage, which was evaluated by the expression of 8-hydroxydeoxyguanosine. Moreover, telmisartan reduced the myocardial apoptosis induced by daunorubicin. Conclusions The present study indicates that telmisartan may improve cardiac function by inhibiting the action of Ang II via AT-1R, which reverses oxidative stress and myocardial apoptosis. This suggests a beneficial effect of telmisartan treatment in the prevention of daunorubicin-induced cardiotoxicity.

Original languageEnglish (US)
Pages (from-to)1776-1783
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume62
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Angiotensin II
  • Cardiotoxicity
  • Daunorubicin
  • Oxidative stress
  • Telmisartan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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