Zhang Qiu Hua, Wu Chun Fu, Duan Lian, Yang Jing Yu
Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Food Chem Toxicol. 2008 Jan;46(1):293-302. doi: 10.1016/j.fct.2007.08.025. Epub 2007 Aug 23.
Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent for the cancer patients to reduce the side effects in the clinic application. Because CP is a pro-oxidant agent and induces oxidative stress by the generation of free radicals to decrease the activities of anti-oxidant enzymes, the protective effects of the total saponins from stem and leaf of P. ginseng C.A. Meyer (TSPG) act as an anti-oxidant agent against the decreased anti-oxidant enzymes, the genotoxicity and apoptosis induced by CP was carried out.
The alkaline single cell gel electrophoresis was employed to detect DNA damage; flow cytometry assay and AO/EB staining assay were employed to measure cell apoptosis; the enzymatic anti-oxidants (T-SOD, CAT and GPx) and non-enzymatic anti-oxidant (GSH) were measured by the various colorimetric methods.
CP induced the significant DNA damage in mouse peripheral lymphocytes in time- and dose-dependent manners, inhibited the activities of T-SOD, GPx and CAT, and decreased the contents of GSH in mouse blood, triggered bone marrow cell apoptosis at 6 and 12h. TSPG significantly reduced CP-induced DNA damages in bone marrow cells and peripheral lymphocyte cells, antagonized CP-induced reduction of T-SOD, GPx, CAT activities and the GSH contents, decreased the bone marrow cell apoptosis induced by CP.
TSPG, significantly reduced the genotoxicity of CP in bone marrow cells and peripheral lymphocyte cells, and decreased the apoptotic cell number induced by CP in bone marrow cells. The effects of TSPG on T-SOD, GPx, CAT activities and GSH contents might partially contribute to its protective effects on CP-induced cell toxicities.
环磷酰胺(CP)是常用的抗癌药物,可诱导氧化应激,对正常细胞具有细胞毒性。选择与CP联合使用的保护剂以减少癌症治疗中的副作用非常重要。人参皂苷是人参的生物活性成分,在临床应用中作为滋补剂用于癌症患者以减轻副作用。由于CP是一种促氧化剂,通过产生自由基诱导氧化应激,从而降低抗氧化酶的活性,因此研究了人参茎叶总皂苷(TSPG)作为抗氧化剂对CP诱导的抗氧化酶活性降低、遗传毒性和细胞凋亡的保护作用。
采用碱性单细胞凝胶电泳检测DNA损伤;采用流式细胞术和AO/EB染色法检测细胞凋亡;采用各种比色法测定酶促抗氧化剂(T-SOD、CAT和GPx)和非酶促抗氧化剂(GSH)。
CP以时间和剂量依赖性方式诱导小鼠外周淋巴细胞显著的DNA损伤,抑制T-SOD、GPx和CAT的活性,降低小鼠血液中GSH的含量,在6小时和12小时触发骨髓细胞凋亡。TSPG显著降低CP诱导的骨髓细胞和外周淋巴细胞的DNA损伤,拮抗CP诱导的T-SOD、GPx、CAT活性降低和GSH含量降低,减少CP诱导的骨髓细胞凋亡。
TSPG显著降低CP对骨髓细胞和外周淋巴细胞的遗传毒性,并减少CP诱导的骨髓细胞凋亡细胞数。TSPG对T-SOD、GPx、CAT活性和GSH含量的影响可能部分有助于其对CP诱导的细胞毒性的保护作用。