Protective effects of ginsenoside Rg(3) against cyclophosphamide-induced DNA damage and cell apoptosis in mice.
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.
Zhang
Qiu Hua
QH
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Wu
Chun Fu
CF
Duan
Lian
L
Yang
Jing Yu
JY
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity*; D053960:DNA Breaks / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D036145:Ginsenosides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; D036145:Ginsenosides; C097367:ginsenoside Rg3; D008315:Malondialdehyde; D003520:Cyclophosphamide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase