Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats.
Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats.
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DOI：
10.1155/2012/434195
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发表时间：
2012
影响因子：
--
通讯作者：
Alhaider A
中科院分区：
文献类型：
--
作者：
Ashour AE;Sayed-Ahmed MM;Abd-Allah AR;Korashy HM;Maayah ZH;Alkhalidi H;Mubarak M;Alhaider A
阿霉素（DOX）的临床使用因其心脏毒性副作用而受到限制。最近的研究表明，二甲双胍（MET）是一种口服抗糖尿病药物，具有抗氧化活性。然而，它是否可以防止阿霉素引起的能量饥饿和线粒体损伤尚未见报道。我们在 DOX 诱导的心脏毒性大鼠模型中的结果表明，DOX 治疗显着增加了心脏损伤指标 LDH 和 CK-MB 的血清水平，并诱导肥厚基因标记物的表达。 DOX 还导致心脏谷胱甘肽、CoA-SH 和 ATP 水平以及过氧化氢酶和 NQO-1 mRNA 表达显着降低。分别通过光学和电子显微镜观察到，这些生化变化与心肌组织病理学和超微结构恶化相关。与 MET（500mg/kg）共同治疗消除了所有 DOX 诱导的生化、组织病理学和超微结构变化。这些发现表明，MET 通过抑制 DOX 诱导的氧化应激、能量饥饿和线粒体内 CoA-SH 的消耗，成功预防 DOX 诱导的体内心脏毒性。
Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.
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影响因子：
6.1
作者：
Berthiaume, J. M.;Wallace, K. B.
通讯作者：
Wallace, K. B.
影响因子：
2.8
作者：
Büyükokuroglu, ME;Taysi, S;Bakan, E
通讯作者：
Bakan, E
DOI：
10.1016/0031-6989(85)90097-9
发表时间：
1985-01-01
期刊：
PHARMACOLOGICAL RESEARCH COMMUNICATIONS
影响因子：
--
作者：
DELEERS, M;GOORMAGHTIGH, E
通讯作者：
GOORMAGHTIGH, E
影响因子：
5
作者：
BOTKER, HE;KIMOSE, HH;NIELSEN, TT
通讯作者：
NIELSEN, TT
影响因子：
5.8
作者：
Anurag, P;Anuradha, CV
通讯作者：
Anuradha, CV