Gholami Saman, Hosseini Mir-Jamal, Jafari Leila, Omidvar Fatemeh, Kamalinejad Mohammad, Mashayekhi Vida, Hosseini Seyed Hojjat, Kardan Azin, Pourahmad Jalal, Eskandari Mohammad Reza
Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Drug Res (Stuttg). 2017 Jun;67(6):358-365. doi: 10.1055/s-0043-101824. Epub 2017 Mar 20.
Quince (Cydonia oblonga Mill.) and fig (Ficus carica L.) exhibit a broad spectrum of pharmacological activities. Regarding the cardiotoxic effect of doxorubicin (DOX) is mediated mainly through mitochondrial oxidative stress and dysfunction; the present study evaluated the cardioprotective effects of the aqueous extracts of Cydonia oblonga Mill. fruit (ACO) and Ficus carica L. fruit (AFC) against DOX-induced cardiotoxicity. Cardiomyocytes toxicity was induced in male Sprague Dawley rats by intraperitoneal (ip) injections of 2.5 mg/kg DOX 3 times per week for a period of 2 weeks. After heart failure was induced in the rats, the animals were decapitated and their hearts were immediately removed. Then, the cardiac mitochondria were isolated by differential ultracentrifugation, and the protective effects of each particular extract on mitochondrial oxidative stress and dysfunction were determined. ACO and AFC ameliorated mitochondrial dysfunction in the isolated mitochondria and prevented mitochondrial reactive oxygen species formation, membrane lipid peroxidation, mitochondrial swelling, mitochondrial membrane potential collapse (%ΔΨm), and cytochrome c release. Also, the extracts significantly increased reduced glutathione levels and succinate dehydrogenase activity. These results indicated that ACO and AFC have beneficial effects against DOX cardiotoxicity which mediated by attenuating mitochondrial dysfunction. Therefore, it can be suggested that quince and fig may increase the therapeutic index of DOX.
榅桲(Cydonia oblonga Mill.)和无花果(Ficus carica L.)具有广泛的药理活性。鉴于阿霉素(DOX)的心脏毒性作用主要通过线粒体氧化应激和功能障碍介导;本研究评估了榅桲果实水提取物(ACO)和无花果果实水提取物(AFC)对DOX诱导的心脏毒性的心脏保护作用。通过每周3次腹腔注射2.5mg/kg DOX,连续2周,诱导雄性Sprague Dawley大鼠的心肌细胞毒性。在大鼠诱导心力衰竭后,将动物断头并立即取出心脏。然后,通过差速超速离心分离心脏线粒体,并测定每种特定提取物对线粒体氧化应激和功能障碍的保护作用。ACO和AFC改善了分离线粒体中的线粒体功能障碍,并防止了线粒体活性氧的形成、膜脂质过氧化、线粒体肿胀、线粒体膜电位崩溃(%ΔΨm)和细胞色素c释放。此外,提取物显著提高了还原型谷胱甘肽水平和琥珀酸脱氢酶活性。这些结果表明,ACO和AFC对DOX心脏毒性具有有益作用,其通过减轻线粒体功能障碍介导。因此,可以认为榅桲和无花果可能会提高DOX的治疗指数。