Allicin enhances chemotherapeutic response and ameliorates tamoxifen-induced liver injury in experimental animals
Allicin enhances chemotherapeutic response and ameliorates tamoxifen-induced liver injury in experimental animals
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DOI：
10.3109/13880209.2013.876053
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发表时间：
2014-07
影响因子：
3.8
通讯作者：
G. Suddek
中科院分区：
文献类型：
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作者：
G. Suddek
摘要背景：他莫昔芬（TAM）广泛用于治疗激素依赖性乳腺癌；然而，它可能伴有肝损伤。大蒜素是大蒜中最丰富的硫代亚磺酸盐分子，有可能对多种疾病产生有益作用。目的：阐明市售大蒜素对 TAM 的抗肿瘤活性和肝损伤的影响。材料和方法：使用培养的艾氏腹水癌 (EAC) 细胞在体外评估 TAM 和/或大蒜素的细胞毒性，并在体内针对 EAC 的鼠肿瘤（实体）模型评估 TAM 和/或大蒜素的细胞毒性。 TAM 通过腹膜内 (i.p.) 注射剂量 45 mg/kg 连续 7 天诱导大鼠肝损伤。结果：3 µM (IC50) 剂量的 TAM 显着降低 EAC 的存活率至 52%。与 TAM 治疗组相比，TAM 与大蒜素（5 或 10 µM）组合显示出显着的细胞毒性作用，EAC 存活率分别下降至 35% 和 29%。大蒜素（10 mg/kg，口服）增强了 TAM（1 mg/kg，腹腔注射）对小鼠的疗效，实体瘤生长抑制显着增加 82%，而 TAM 组为 70%。在大鼠中，TAM中毒导致SOD、GSH和总蛋白显着下降，而TBARS、ALT和AST、ALP、LDH、总胆红素、γGT和TNF-α水平显着升高。这些变化可通过大蒜素治疗消除。讨论和结论：结果表明大蒜素作为 TAM 的佐剂通过减轻肝损伤在癌症治疗中发挥有益作用。
Abstract Context: Tamoxifen (TAM) is widely used for treatment of hormone-dependent breast cancer; however, it may be accompanied with hepatic injury. Allicin is the most abundant thiosulfinate molecule from garlic with the potential to provide beneficial effects on various diseases. Objective: To elucidate the effect of commercially available allicin on both antitumor activity and liver injury of TAM. Materials and methods: The cytotoxicity of TAM and/or allicin was evaluated in vitro using cultured Ehrlich ascites carcinoma (EAC) cells and in vivo against murine tumor (solid) model of EAC. TAM induced liver injury in rats by intraperitoneally (i.p.) injection at a dose of 45 mg/kg, for 7 successive days. Results: TAM at a dose of 3 µM (IC50) significantly decreased percent survival of EAC to 52%. TAM combination with allicin (5 or 10 µM) showed a significant cytotoxic effect compared with the TAM-treated group as manifested by a decrease in percent survival of EAC to 35% and 29%, respectively. Allicin (10 mg/kg, orally) enhanced the efficacy of TAM (1 mg/kg, i.p.) in mice as manifested by a significant increase in solid tumor growth inhibition by 82% compared with 70% in the TAM group. In rats, TAM intoxication resulted in a significant decline in SOD, GSH, and total protein with significant elevation in TBARS, ALT and AST, ALP, LDH, total bilirubin, γGT, and TNF-α levels. These changes are abrogated by allicin treatment. Discussion and conclusion: The results suggest the beneficial role of allicin as an adjuvant to TAM in cancer treatment by alleviating liver injury.