Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response
Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response
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DOI：
10.1016/j.fct.2015.02.009
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发表时间：
2015-04-01
影响因子：
4.3
通讯作者：
Konishi, Hiroki
中科院分区：
文献类型：
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作者：
Nagai, Katsuhito;Oda, Ayano;Konishi, Hiroki
多柔比星（DOX）被广泛用作具有拓扑异构酶II抑制活性的抗肿瘤剂;然而，由于剂量相关的器官损伤，其给药的剂量和持续时间受到严格限制。本研究探讨了茶氨酸，一种在绿色茶叶中发现的氨基酸，是否可以减少阿霉素诱导的小鼠急性肝毒性和细胞凋亡反应。在给予20 mg/kg DOX后，血清中天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）（肝损伤的生物标志物）的活性显著增加，而这些升高的程度被10 mg/kg茶氨酸显著减弱，这与通过显微镜检查评估的组织学肝脏图像一致。Bax和Fas的肝脏表达，代表内在和外在的凋亡分子，分别与DOX给药，显着增加。然而，在肝脏表达的Bax，但不是Fas的升高，被抑制到控制水平的茶氨酸。DOX与茶氨酸联合治疗组的caspase-3裂解蛋白的形成明显低于单独DOX治疗组。这些结果表明，茶氨酸对DOX诱导的急性肝损伤具有保护作用，其机制可能与抑制内源性caspase-3依赖的凋亡信号有关。(C)2015爱思唯尔有限公司版权所有。
Doxorubicin (DOX) is widely used as an antitumor agent with topoisomerase II inhibiting activity; however, its dosage and duration of administration have been strictly limited due to dose-related organ damage. The present study investigated whether theanine, an amino acid found in green tea leaves, could reduce DOX-induced acute hepatotoxicity and the apoptotic response in mice. Activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, biomarkers of hepatic impairment, were markedly increased after the administration of 20 mg/kg DOX, whereas the degree of these elevations was significantly attenuated by 10 mg/kg theanine, which was consistent with histological hepatic images assessed by microscopic examination. The hepatic expression of Bax and Fas, representative intrinsic and extrinsic apoptotic molecules, respectively, was significantly increased by dosing with DOX. However, the elevation in the hepatic expression of Bax, but not Fas, was suppressed to control levels by theanine. The formation of cleaved caspase-3 protein in the group given DOX with theanine was significantly lower than that in the group treated with DOX alone. These results suggest that theanine can protect against acute hepatic damage induced by DOX, which is attributed to the suppression of intrinsic caspase-3dependent apoptotic signaling. (C) 2015 Elsevier Ltd. All rights reserved.