Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Food Chem Toxicol. 2010 May;48(5):1178-84. doi: 10.1016/j.fct.2010.02.008. Epub 2010 Feb 8.
Doxorubicin (DOX) is a widely used cancer chemotherapeutic agent. However, it generates free oxygen radicals that result in serious dose-limiting cardiotoxicity. Supplementations with berries were proven effective in reducing oxidative stress associated with several ailments. The aim of the current study was to investigate the potential protective effect of cranberry extract (CRAN) against DOX-induced cardiotoxicity in rats. CRAN was given orally to rats (100mg/kg/day for 10 consecutive days) and DOX (15mg/kg; i.p.) was administered on the seventh day. CRAN protected against DOX-induced increased mortality and ECG changes. It significantly inhibited DOX-provoked glutathione (GSH) depletion and accumulation of oxidized glutathione (GSSG), malondialdehyde (MDA), and protein carbonyls in cardiac tissues. The reductions of cardiac activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were significantly mitigated. Elevation of cardiac myeloperoxidase (MPO) activity in response to DOX treatment was significantly hampered. Pretreatment of CRAN significantly guarded against DOX-induced rise of serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), creatine kinase-MB (CK-MB) as well as troponin I level. CRAN alleviated histopathological changes in rats' hearts treated with DOX. In conclusion, CRAN protects against DOX-induced cardiotoxicity in rats. This can be attributed, at least in part, to CRAN's antioxidant activity.
多柔比星（DOX）是一种广泛应用的癌症化疗药物。然而，它会产生自由基，导致严重的剂量限制的心脏毒性。浆果补充剂已被证明可有效减轻与多种疾病相关的氧化应激。本研究旨在探讨蔓越莓提取物（CRAN）对大鼠多柔比星诱导的心脏毒性的潜在保护作用。CRAN 经口给予大鼠（连续 10 天每天 100mg/kg），第 7 天给予多柔比星（15mg/kg；腹腔注射）。CRAN 可预防多柔比星引起的死亡率增加和心电图变化。它显著抑制多柔比星引起的谷胱甘肽（GSH）耗竭以及氧化型谷胱甘肽（GSSG）、丙二醛（MDA）和心脏组织中蛋白质羰基的积累。心脏组织中过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和谷胱甘肽还原酶（GR）的活性降低也得到显著缓解。多柔比星处理引起的心脏髓过氧化物酶（MPO）活性升高也受到显著抑制。CRAN 预处理可显著防止 DOX 引起的血清乳酸脱氢酶（LDH）、肌酸磷酸激酶（CK）、肌酸激酶同工酶-MB（CK-MB）和肌钙蛋白 I 水平升高。CRAN 减轻了 DOX 处理大鼠心脏的组织学变化。总之，CRAN 可预防大鼠多柔比星诱导的心脏毒性。这至少部分归因于 CRAN 的抗氧化活性。
