Zhang Qiu Hua, Wu Chun Fu, Duan Lian, Yang Jing Yu
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Arch Toxicol. 2008 Feb;82(2):117-23. doi: 10.1007/s00204-007-0224-3. Epub 2007 Jun 28.
Despite the significant anti-tumor activities, cyclophosphamide (CP) also shows cytotoxicity to normal cells. In order to explore the protective effects of drugs against CP-induced adverse effects, 20(S)-ginsenoside Rg(3) was tested for its possibly protective activities on CP-induced DNA damage and cell apoptosis in mouse bone marrow cells or peripheral lymphocyte cells. In the current study, the alkaline single cell gel electrophoresis (comet assay), flow cytometry assay with annexin V-FITC/PI and AO/EB staining assay were employed to measure DNA strand breakage and cell apoptosis, respectively. The activities of SOD and GPx and the contents of MDA were also tested by the various colormetric methods. The results showed that CP at a dose of 100 mg/kg, i.p. significantly caused DNA damages in both mouse bone marrow cells and peripheral lymphocyte cells, and markedly inhibited the activities of GPx and SOD and increased MDA contents in mouse blood. Moreover, CP at a dose of 200 mg/kg, i.p. triggered apoptosis in mouse bone marrow cells. On the other hand, 20(S)-ginsenoside Rg(3) orally administered at a dose of 20 mg/kg to the animals once a day for 2 days significantly inhibited CP-induced DNA damages in mouse bone marrow cells and peripheral lymphocyte cells, decrease the apoptotic numbers of bone marrow cells, antagonized the reduction of the activities of SOD and GPx, and the increase in MDA contents. In conclusion, 20(S)-ginsenoside Rg(3) showed the significant protective effects on CP-induced cell DNA damage and apoptosis. These effects might be partially attributed to its protective actions against CP-induced oxidative stress.
尽管环磷酰胺（CP）具有显著的抗肿瘤活性，但它对正常细胞也表现出细胞毒性。为了探索药物对CP诱导的不良反应的保护作用，测试了20（S）-人参皂苷Rg3对CP诱导的小鼠骨髓细胞或外周淋巴细胞DNA损伤和细胞凋亡的潜在保护活性。在本研究中，分别采用碱性单细胞凝胶电泳（彗星试验）、 annexin V-FITC/PI流式细胞术检测和AO/EB染色检测来测量DNA链断裂和细胞凋亡。还通过各种比色法检测了SOD和GPx的活性以及MDA的含量。结果表明，腹腔注射100mg/kg剂量的CP显著导致小鼠骨髓细胞和外周淋巴细胞的DNA损伤，并明显抑制GPx和SOD的活性，增加小鼠血液中MDA的含量。此外，腹腔注射200mg/kg剂量的CP可引发小鼠骨髓细胞凋亡。另一方面，以20mg/kg的剂量每天给动物口服一次20（S）-人参皂苷Rg3，连续2天，可显著抑制CP诱导的小鼠骨髓细胞和外周淋巴细胞的DNA损伤，减少骨髓细胞的凋亡数量，拮抗SOD和GPx活性的降低以及MDA含量的增加。总之，20（S）-人参皂苷Rg3对CP诱导的细胞DNA损伤和凋亡具有显著的保护作用。这些作用可能部分归因于其对CP诱导的氧化应激的保护作用。
