Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Qiu Hua
QH
Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Wu
Chun Fu
CF
Duan
Lian
L
Yang
Jing Yu
JY
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002374:Catalase / Q000097:blood; D020552:Comet Assay; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D005894:Panax / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D012503:Saponins / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000097:blood
D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D005456:Fluorescent Dyes; D009153:Mutagens; D012503:Saponins; D003520:Cyclophosphamide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D016650:Fluorescein-5-isothiocyanate