Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats
Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats
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DOI：
10.3109/10715762.2010.509399
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Aizawa, Yoshifusa
中科院分区：
文献类型：
--
作者：
Arozal, Wawaimuli;Watanabe, Kenichi;Aizawa, Yoshifusa
目的是评价奥美沙坦（血管紧张素II（Ang II）受体阻滞剂（ARB））与柔红霉素（DNR）联合用药在降低大鼠心脏毒性中的作用。DNR以3 mg/kg/天的剂量隔日给药，持续12天。奥美沙坦每日口服给药，持续12天。DNR单独治疗的大鼠显示心脏毒性，表现为心脏功能恶化、心脏组织中丙二醛水平升高和总谷胱甘肽过氧化物酶活性水平降低; ARB治疗逆转了这些变化。此外，ARB治疗下调基质金属蛋白酶-2的表达，心肌血管紧张素II的表达，减弱p67（phox）和Nox 4蛋白表达的增加，减少氧化应激诱导的DNA损伤的8-羟基脱氧鸟苷的表达。总之，结果表明，血管紧张素II和氧化应激在蒽环类药物诱导的心脏毒性中起关键作用，ARB治疗将有利于对抗DNR诱导的心脏毒性。
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 p67(phox) 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.