Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Phytother Res. 2022 Jan;36(1):506-524. doi: 10.1002/ptr.7356. Epub 2021 Dec 27.
The main adverse effect of doxorubicin is cardiotoxicity. Oxidative stress and apoptosis induction have been suggested as mechanisms involved in its cardiotoxicity. In this study, cardioprotective effects of alpha-mangostin against doxorubicin-induced cardiotoxicity have been investigated in rats. Forty-two rats were divided as follows: Control, doxorubicin (2 mg/kg every 48 hr), alpha-mangostin (200 mg/kg), alpha-mangostin (50, 100, 200 mg/kg) + doxorubicin (2 mg/kg every 48 hr), and vitamin E (200 IU/kg) + doxorubicin (2 mg/kg every 48 hr). Alpha-mangostin was administered by gavage for 19 days, while doxorubicin (12 days) and vitamin E (19 days) were injected intraperitoneally. Doxorubicin decreased heart rate, increased electrocardiogram signal components duration and reduced systolic and diastolic arterial blood pressure, and caused histological damage in the heart of rats. Doxorubicin decreased heart weight and heart/body weight ratio, as well as elevated creatine phosphokinase isoenzyme and lactate dehydrogenase. Doxorubicin increased malondialdehyde, inflammatory biomarkers, and caspases 3 and 9 and decreased reduced glutathione content in heart tissue but co-administration of alpha-mangostin (100 mg/kg) restored all doxorubicin toxic effects. Results show that alpha-mangostin has protective effects against doxorubicin-induced cardiotoxicity by antioxidant, antiinflammatory, and antiapoptotic effects that may ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect.
阿霉素的主要不良反应是心脏毒性。氧化应激和细胞凋亡诱导被认为是其心脏毒性的机制。在这项研究中，研究了α-倒捻子素对阿霉素诱导的大鼠心脏毒性的心脏保护作用。将 42 只大鼠分为以下几组：对照组、阿霉素（2mg/kg，每 48 小时一次）、α-倒捻子素（200mg/kg）、α-倒捻子素（50、100、200mg/kg）+阿霉素（2mg/kg，每 48 小时一次）和维生素 E（200IU/kg）+阿霉素（2mg/kg，每 48 小时一次）。α-倒捻子素通过灌胃给药 19 天，而阿霉素（12 天）和维生素 E（19 天）则通过腹腔注射。阿霉素降低心率，增加心电图信号成分持续时间，降低收缩压和舒张压，并导致大鼠心脏组织的组织学损伤。阿霉素降低心脏重量和心脏/体重比，并升高肌酸磷酸激酶同工酶和乳酸脱氢酶。阿霉素增加丙二醛、炎症生物标志物、caspase 3 和 9，并降低心脏组织中的还原型谷胱甘肽含量，但α-倒捻子素（100mg/kg）的联合给药可恢复阿霉素的所有毒性作用。结果表明，α-倒捻子素通过抗氧化、抗炎和抗凋亡作用对阿霉素诱导的心脏毒性具有保护作用，可能改善人类化疗中的阿霉素心脏毒性，而不降低其抗癌作用。
