Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Food Chem Toxicol. 2010 Mar;48(3):951-6. doi: 10.1016/j.fct.2010.01.005. Epub 2010 Jan 12.
Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis. In this study we investigated whether aged garlic has protective effects against doxorubicin-induced free radical production and cardiotoxicity in male rats. A single dose of doxorubicin (25mg/kg) caused increased both serum cardiac enzymes LDH and CPK activities and a significant increase malonyldialdehyde (MDA) in plasma. However, pretreatment of rats with aged garlic extract (250 mg/kg) for 27 days before doxorubicin therapy, reduced the activity of both enzymes, and significantly decreased of MDA production in plasma. Total antioxidant activity was increased after aged garlic extract administration. Histopathological examination of heart tissue showed that DOX treatment resulted in alteration of cardiac tissue structure in the form of peri arterial fibrosis and apoptotic changes in cardiomyocytes. Pretreatment with aged garlic extract for 27 days ameliorated the effect of DOX administration on cardiac tissue; cardiomyocytes looked more or less similar to those of control. However, still vascular dilatation, mild congestion and interstitial edemas were observed. Our results suggest that aged garlic extract is potentially protective against doxorubicin-induced cardiotoxicity.
阿魏酸（FA）是一种天然存在的酚酸，具有多种生物活性，包括抗氧化、抗炎和抗凋亡特性。本研究旨在探讨 FA 对 DOX 诱导的心肌细胞损伤的保护作用及其可能的机制。
我们将 H9c2 心肌细胞分为对照组、DOX 组（100μM DOX）、FA 预处理组（100μM FA 预处理 24 小时，然后加入 100μM DOX）和 FA+LY294002 组（100μM FA 预处理 24 小时，然后加入 100μM DOX 和 20μM LY294002）。用 MTT 法检测细胞活力，用 Hoechst 33342 染色和流式细胞术检测细胞凋亡，用 Western blot 检测凋亡相关蛋白（Bax、Bcl-2、cleaved caspase-3）的表达。
结果显示，DOX 处理显著降低了 H9c2 心肌细胞的活力，并诱导了细胞凋亡。FA 预处理显著抑制了 DOX 诱导的细胞活力下降和凋亡。此外，FA 预处理还抑制了 DOX 诱导的 Bax 和 cleaved caspase-3 蛋白的表达增加，同时增加了 Bcl-2 蛋白的表达。
我们的研究结果表明，FA 对 DOX 诱导的心肌细胞损伤具有保护作用，其机制可能与抑制细胞凋亡有关。
