Dias Marcos C, Rodrigues Maria A M, Reimberg Maria C H, Barbisan Luís F
UNESP São Paulo State University, Institute of Biosciences, Department of Morphology, Botucatu, SP 18618-000, Brazil.
Chem Biol Interact. 2008 May 9;173(1):32-42. doi: 10.1016/j.cbi.2008.01.012. Epub 2008 Feb 12.
Ginkgo biloba (EGb) has been proposed as a promising candidate for cancer chemoprevention and has shown protective effects on the liver against chemically induced oxidative injury and fibrosis. The potential beneficial effects of EGb were investigated in two rat liver carcinogenesis bioassays induced by diethylnitrosamine (DEN). In a short-term study for anti-initiating screening, male Wistar rats were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb and initiated 14 days later with a single dose of DEN (100 mg/kg i.p.). The respective groups were killed 24h or 2 weeks after DEN-initiation. Liver samples were collected for the analysis of proliferating cell nuclear antigen (PCNA), transforming growth factor alpha (TGF-alpha), p53, apoptosis and induction of single hepatocytes and minifoci positive for the enzyme glutathione S-transferase P-form (GST-P). In a medium-term study for anti-promoting screening, the animals received a single dose of DEN (200 mg/kg i.p.) and, 2 weeks later, were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb for 6 weeks. All animals underwent 70% partial hepatectomy (PH) at week 3 and killed at week 8. Liver samples were collected to analyze development of preneoplastic foci of altered hepatocytes (FAH) expressing GST-P. In the short-term study, pretreatment of rats with 1000 ppm EGb significantly reduced the rates of cell proliferation, apoptosis and p53, TGF-alpha immunoreactivity and the number of GST-P-positive hepatocytes. In the medium-term study, EGb treatment during the post-initiation stage failed to reduce the development of DEN-induced GST-P-positive foci. Thus, EGb presented inhibitory actions during initiation but not promotion of rat liver carcinogenesis induced by DEN.
银杏叶提取物（EGb）已被认为是癌症化学预防的一个有前景的候选物，并且已显示出对肝脏具有保护作用，可抵抗化学诱导的氧化损伤和纤维化。在由二乙基亚硝胺（DEN）诱导的两种大鼠肝癌发生生物测定中研究了EGb的潜在有益作用。在一项用于抗启动筛选的短期研究中，给雄性Wistar大鼠喂食基础饮食或添加500或1000 ppm EGb的饮食，14天后单次腹腔注射DEN（100 mg/kg）进行启动。在DEN启动后24小时或2周处死各个组。收集肝脏样本用于分析增殖细胞核抗原（PCNA）、转化生长因子α（TGF-α）、p53、凋亡以及单个肝细胞和对谷胱甘肽S-转移酶P型（GST-P）呈阳性的微小病灶的诱导情况。在一项用于抗促进筛选的中期研究中，动物接受单次腹腔注射DEN（200 mg/kg），2周后，给它们喂食基础饮食或添加500或1000 ppm EGb的饮食，持续6周。所有动物在第3周接受70%部分肝切除术（PH），并在第8周处死。收集肝脏样本以分析表达GST-P的癌前肝细胞灶（FAH）的发展情况。在短期研究中，用1000 ppm EGb预处理大鼠可显著降低细胞增殖率、凋亡率以及p53、TGF-α免疫反应性和GST-P阳性肝细胞的数量。在中期研究中，启动后阶段的EGb治疗未能减少DEN诱导的GST-P阳性病灶的发展。因此，EGb在DEN诱导的大鼠肝癌发生的启动阶段呈现抑制作用，但在促进阶段则没有。
