Key result
Isorhamnetin pretreatment significantly protected against doxorubicin-induced cardiotoxicity, reducing the rate of TUNEL-positive apoptotic cells from 62.70% to 22.17%.
Why the study?
Does isorhamnetin prevent doxorubicin-induced cardiotoxicity in preclinical in vivo and in vitro models?
Does isorhamnetin prevent doxorubicin-induced cardiotoxicity in preclinical in vivo and in vitro models?
Isorhamnetin demonstrates cardioprotective effects against doxorubicin-induced toxicity in preclinical models, suggesting potential as an adjuvant therapy in cardio-oncology.
Answers are grounded in this paper and cite their sources.
Does not support clinical use; leaves open isorhamnetin cardioprotection in doxorubicin-treated patients pending human trials.
Doxorubicin (Dox) is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. Isorhamnetin is a nature antioxidant with obvious cardiac protective effect. The aim of this study is going to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p.) administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity. Daily pretreatment with isorhamnetin (5 mg/kg, i.p.) for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. A further mechanism study indicated that isorhamnetin pretreatment can counteract Dox-induced oxidative stress and suppress the activation of mitochondrion apoptotic pathway and mitogen-activated protein kinase pathway. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox.
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Sun et al. (2013) studied Doxorubicin-induced cardiotoxicity (n=64). Isorhamnetin vs. Doxorubicin alone (3 mg/kg i.p. every other day) was evaluated on TUNEL-positive apoptotic cells in vitro (p=<0.05). Isorhamnetin pretreatment significantly protected against doxorubicin-induced cardiotoxicity, reducing the rate of TUNEL-positive apoptotic cells from 62.70% to 22.17%.
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