Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy.
Eur Rev Med Pharmacol Sci. 2011 Feb;15(2):181-91.
To verify the involvement of free radicals in tumor progression and to investigate the effects of an ethanolic extract of Ruta Chalepensis L. and of rutin in blood of patients with colon cancer.
Leaves of Ruta Chalepensis L. were collected in the area around Catania (Italy). For the preparation of the ethanol extract of leaves, an exhaustive extraction of 100 g of the drug was carried out in Soxhlet with 800 ml of 95% ethanol. Fifty-six patients with colorectal cancer were randomly selected for this study; among these, 34 were affected by an early stage (T1 N0 M0 according to scale), while 22 were affected by an advanced stage (T4, N1-2, M0) of cancer. Data obtained from these patients were compared with those of a control group consisting of 20 healthy subjects. Plasma of each sample was used for determining non-proteic antioxidant capacity, thiol groups, lipid hydroperoxides and nitrite/nitrate levels, evaluated by spectrophotometric tests. In addition, percentage of haemolysis was evaluated incubating (for 2 hours at 37 degrees C) erythrocyte suspension with a free radical donor (50 mM 2,2'-azobis-amidino propane chloridrate), in the presence or absence of ethanolic extract of Ruta Chalepensis L. (250 microg/ml) or rutin (1 mM).
Non-proteic antioxidant capacity was significantly lower in cancerous patients than in healthy subjects (p < 0.001). This decrease was stage-related. In fact, non-proteic antioxidant capacity resulted lower in advanced than in early colorectal cancer (p < 0.001). The same significant stage-related decrease was observed in plasma thiol groups (p < 0.001). Coherently with the decrease in non-proteic antioxidant capacity and thiol groups, higher levels of lipid hydroperoxides and nitrite/nitrate were observed in patients with colorectal cancer with respect to healthy subjects (p < 0.001) and the increase in these markers of oxidative stress was related to the cancer stadiation. Neoplastic patients also showed an increased percentage of oxidative hemolysis respect to controls and the haemolytic damage was correlated with the stage of colon cancer. Both the extract of Ruta Chalepensis L. and rutin were able to protect erythrocytes from oxidative stress induced by the free radical donor, but the extract of Ruta Chalepensis L. was more effective than rutin. This protective effect was significant only in erythrocytes from patients with early colorectal group, whereas no significant modification was induced by Ruta Chalepensis L. or rutin in red blood cells from advanced colorectal cancer patients exposed to the same experimental conditions.
Oxidative stress correlates with colon cancer stadiation and both the extract of Ruta chalepensis and rutin are able to protect red blood cells from radical-induced damage. However, their effects are significant in early stages of cancer. So these natural antioxidants might be usefull to prevent carcinogenesis and/or tumor progression.
验证自由基在肿瘤进展中的作用，并研究野芫荽（Ruta chalepensis L.）的乙醇提取物和芦丁对结肠癌患者血液的影响。
在卡塔尼亚（意大利）附近地区采集野芫荽的叶子。为了制备叶乙醇提取物，用索氏提取器对 100 克药物用 800 毫升 95%乙醇进行了彻底提取。本研究随机选择了 56 名结直肠癌患者；其中 34 名患有早期（根据量表为 T1 N0 M0），22 名患有晚期（T4、N1-2、M0）癌症。将这些患者的数据与由 20 名健康受试者组成的对照组进行比较。用分光光度法检测非蛋白抗氧化能力、巯基、脂质过氧化物和亚硝酸盐/硝酸盐水平，测定每个样本的血浆。此外，通过在 37°C 下孵育（2 小时）红细胞悬浮液与自由基供体（50mM 2,2'-偶氮双（2-脒基丙烷）盐酸盐），在存在或不存在野芫荽（Ruta chalepensis L.）乙醇提取物（250μg/ml）或芦丁（1mM）的情况下，评估红细胞溶血的百分比。
癌症患者的非蛋白抗氧化能力明显低于健康受试者（p<0.001）。这种减少与阶段有关。事实上，晚期结直肠癌患者的非蛋白抗氧化能力明显低于早期（p<0.001）。在血浆巯基中也观察到了同样显著的与阶段相关的减少（p<0.001）。与非蛋白抗氧化能力和巯基的减少一致，与健康受试者相比，结直肠癌患者的脂质过氧化物和亚硝酸盐/硝酸盐水平更高（p<0.001），并且这些氧化应激标志物的增加与癌症分期有关。肿瘤患者的氧化溶血百分比也高于对照组，并且溶血损伤与结肠癌的分期相关。野芫荽提取物和芦丁都能保护红细胞免受自由基供体诱导的氧化应激，但野芫荽提取物比芦丁更有效。这种保护作用仅在早期结直肠组的红细胞中显著，而在暴露于相同实验条件的晚期结直肠癌患者的红细胞中，野芫荽提取物或芦丁没有引起显著变化。
氧化应激与结肠癌分期相关，野芫荽提取物和芦丁都能保护红细胞免受自由基诱导的损伤。然而，它们在癌症的早期阶段效果显著。因此，这些天然抗氧化剂可能有助于预防癌变和/或肿瘤进展。
