Abstract

The toxic side effects of doxorubicin in cancer treatment are well established. Here we show that methanolic extract of the fungus Ganoderma applanatum offers protection against cardio- and hepatotoxicity induced by doxorubicin (DOX) in Dalton’s Lymphoma Ascites (DLA) bearing mice. Treatment of DLA mice with 20 mg/kg of doxorubicin significantly increased the activities of serum toxicity markers including aspartate amino-transferase (AST), alanine amino-transferase (ALT) and lactate dehydrogenase (LDH). However, co-administration of doxorubicin (20 mg/kg) by intraperitoneal injection and G. applanatum (150 mg/kg) by oral gavage in DLA mice lowered the AST, ALT, and LDH activities when compared to DOX alone treatment. Treatment of DLA mice with DOX alone resulted in reduced GSH contents, and decreased the activities of glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD). Treatment of DOX-administered DLA mice with G. applanatum however increased the GSH content and elevated the activities of GST, CAT, and SOD. Among the various solvent extracts of G. applanatum, methanolic extract showed the highest phenolic (376.5 ± 15.24 mg GAE/g) and flavonoid (4717.79 ± 170.22 mg quercetin/g) contents compared to the aqueous (216.3 ± 7.33 mg GAE/g) and chloroform extracts (137.27 ± 1.03 mg GAE/g). Consistently, the methanolic extract was found to possess the highest free radical scavenging activities when compared to the aqueous and chloroform extracts as measured by ABTS and DPPH assays. Our results thus suggest that the protective roles of G. applanatum in DOX-induced toxicity could be an attribute of the antioxidant properties conferred by the high phenolic and flavonoid contents.

摘要

阿霉素在癌症治疗中的毒副作用是公认的。在这里，我们展示了真菌灵芝的甲醇提取物对多柔比星 (DOX) 对道尔顿淋巴瘤腹水 (DLA) 小鼠的心脏和肝毒性提供保护。用 20 mg/kg 多柔比星处理 DLA 小鼠显着增加了血清毒性标志物的活性，包括天冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶 (ALT) 和乳酸脱氢酶 (LDH)。然而，通过腹膜内注射和G. applanatum共同给药多柔比星 (20 mg/kg)与 DOX 单独治疗相比，DLA 小鼠经口管饲法（150 mg/kg）降低了 AST、ALT 和 LDH 活性。单独用 DOX 治疗 DLA 小鼠会导致 GSH 含量降低，并降低谷胱甘肽-s-转移酶 (GST)、过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD) 的活性。然而，用G.applanatum处理 DOX 给药的 DLA 小鼠会增加 GSH 含量并提高 GST、CAT 和 SOD 的活性。在G. applanatum 的各种溶剂提取物中，与水性 (216.3 ± 7.33 mg GAE/g) 和氯仿提取物 (137.27 ± 1.03 mg GAE/g) 相比，甲醇提取物的酚类 (376.5 ± 15.24 mg GAE/g) 和类黄酮 (4717.79 ± 170.22 mg GAE/g) 含量最高G）。与通过 ABTS 和 DPPH 测定法测量的水和氯仿提取物相比，发现甲醇提取物具有最高的自由基清除活性。因此，我们的研究结果表明，G. applanatum在 DOX 诱导的毒性中的保护作用可能是高酚类和类黄酮含量赋予的抗氧化特性的一个属性。