TY - JOUR
T1 - Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats
AU - Arozal, Wawaimuli
AU - Watanabe, Kenichi
AU - Veeraveedu, Punniyakoti T.
AU - Thandavarayan, Rajarajan A.
AU - Harima, Meilei
AU - Sukumaran, Vijayakumar
AU - Suzuki, Kenji
AU - Tachikawa, Hitoshi
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
N1 - Funding Information:
Declaration of interest: This research was supported by a Yujin Memorial Grant, Ministry of Education, Cul ture, Sports and Technology of Japan and by a grant from the Promotion and Mutual Aid Corporation for Private Schools, Japan.
PY - 2010/11
Y1 - 2010/11
N2 - The aim was to evaluate the role of the combination of olmesartan, an angiotensin II (Ang II) receptor blocker (ARB), with daunorubicin (DNR) in reducing cardiac toxicity in rats. DNR was administered at a dose of 3 mg/kg/day every other day for 12 days. Olmesartan was administered orally every day for 12 days. Rats treated with DNR alone showed cardiac toxicity as evidenced by worsening cardiac function, elevation of malondialdehyde level in heart tissue and decreased in the level of total glutathione peroxidase activity; treatment with ARB reversed these changes. Furthermore, ARB treatment down-regulated matrix metalloproteinase-2 expression, myocardial expression of Ang II, attenuated the increased protein expressions of p67phox and Nox4 and reduced oxidative stress-induced DNA damage evaluated by expression of 8-hydroxydeoxyguanosine. In conclusion, the result demonstrated that Ang II and oxidative stress play a key role in anthracycline-induced cardiotoxicity and that treatment with ARB will be beneficial against DNR-induced cardiotoxicity.
AB - The aim was to evaluate the role of the combination of olmesartan, an angiotensin II (Ang II) receptor blocker (ARB), with daunorubicin (DNR) in reducing cardiac toxicity in rats. DNR was administered at a dose of 3 mg/kg/day every other day for 12 days. Olmesartan was administered orally every day for 12 days. Rats treated with DNR alone showed cardiac toxicity as evidenced by worsening cardiac function, elevation of malondialdehyde level in heart tissue and decreased in the level of total glutathione peroxidase activity; treatment with ARB reversed these changes. Furthermore, ARB treatment down-regulated matrix metalloproteinase-2 expression, myocardial expression of Ang II, attenuated the increased protein expressions of p67phox and Nox4 and reduced oxidative stress-induced DNA damage evaluated by expression of 8-hydroxydeoxyguanosine. In conclusion, the result demonstrated that Ang II and oxidative stress play a key role in anthracycline-induced cardiotoxicity and that treatment with ARB will be beneficial against DNR-induced cardiotoxicity.
KW - Daunorubicin
KW - angiotensin II receptor blocker
KW - cardiotoxicity
KW - olmesartan
KW - oxidative stress
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U2 - 10.3109/10715762.2010.509399
DO - 10.3109/10715762.2010.509399
M3 - Article
C2 - 20815778
AN - SCOPUS:77957962066
SN - 1071-5762
VL - 44
SP - 1369
EP - 1377
JO - Free Radical Research
JF - Free Radical Research
IS - 11
ER -