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.
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 daunorubicincardiotoxic 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.
Authors: Szabolcs Gergely; Csaba Hegedűs; Petra Lakatos; Katalin Kovács; Renáta Gáspár; Tamás Csont; László Virág Journal: Oxid Med Cell Longev Date: 2015-06-07 Impact factor: 6.543
Authors: Nabil E Boutagy; Attila Feher; Daniel Pfau; Zhao Liu; Nicole M Guerrera; Lisa A Freeburg; Sydney J Womack; Abigail C Hoenes; Caroline Zeiss; Lawrence H Young; Francis G Spinale; Albert J Sinusas Journal: JACC CardioOncol Date: 2020-12-22
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Authors: Marilisa Molinaro; Pietro Ameri; Giancarlo Marone; Mario Petretta; Pasquale Abete; Fabio Di Lisa; Sabino De Placido; Domenico Bonaduce; Carlo G Tocchetti Journal: Biomed Res Int Date: 2015-10-25 Impact factor: 3.411