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

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 3 mg/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 p22(phox), p47(phox), p67(phox), 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.