Suddek Ghada M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt.
Pharm Biol. 2014 Aug;52(8):1009-14. doi: 10.3109/13880209.2013.876053. Epub 2014 Mar 19.
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.
To elucidate the effect of commercially available allicin on both antitumor activity and liver injury of TAM.
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.
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.
The results suggest the beneficial role of allicin as an adjuvant to TAM in cancer treatment by alleviating liver injury.
他莫昔芬（TAM）被广泛用于治疗激素依赖性乳腺癌；然而，它可能会伴有肝损伤。大蒜素是大蒜中含量最丰富的硫代亚磺酸盐分子，对多种疾病具有潜在的有益作用。
阐明市售大蒜素对TAM抗肿瘤活性和肝损伤的影响。
使用培养的艾氏腹水癌细胞在体外评估TAM和/或大蒜素的细胞毒性，并在体内评估其对艾氏腹水癌小鼠肿瘤（实体）模型的作用。通过腹腔注射（i.p.）以45mg/kg的剂量连续7天给大鼠注射TAM诱导肝损伤。
3μM（IC50）剂量的TAM显著降低了艾氏腹水癌的存活率至52%。与TAM治疗组相比，TAM与大蒜素（5或10μM）联合使用显示出显著的细胞毒性作用，艾氏腹水癌的存活率分别降至35%和29%。大蒜素（10mg/kg，口服）增强了TAM（1mg/kg，腹腔注射）对小鼠的疗效，实体瘤生长抑制率显著提高82%，而TAM组为70%。在大鼠中，TAM中毒导致超氧化物歧化酶、谷胱甘肽和总蛋白显著下降，丙二醛、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、乳酸脱氢酶、总胆红素、γ-谷氨酰转移酶和肿瘤坏死因子-α水平显著升高。大蒜素治疗可消除这些变化。
结果表明大蒜素作为TAM的辅助剂在癌症治疗中具有有益作用，可减轻肝损伤。
