Therapeutic effects of Medicago sativa against cyclophosphamide-induced toxicity in rats

Objective: Medicago sativa (M. sativa) has been traditionally used for treating anemia; therefore, M. sativa hydro-ethanolic extract therapeutic effects against cyclophosphamide (CP) -induced hematologic and liver toxicity were examined. Materials and Methods: Thirty male Wistar rats were randomly divided to control (saline); CP (۱۰۰ mg/kg, day ۱-۳, subcutaneously); CP+ M. sativa ۲۰۰ mg/kg (MS ۲۰۰); CP+ M. sativa ۴۰۰ mg/kg (MS ۴۰۰); CP+ dexamethasone (۰.۱ mg/kg), (all groups n=۶). Treated animals received M. sativa or dexamethasone by gavage from days ۷-۱۴. On days ۰, ۷, and ۱۴, hematologic parameters, and on the ۱۴th day, serum and liver tissue oxidative stress markers including nitric oxide, malondialdehyde (MDA) and total thiol levels, superoxide dismutase (SOD) and catalase (CAT) activities, serum lipids, and liver enzymes were measured.Results: Animal weight, platelet, white blood cells, and red blood cells counts, hemoglobin and hematocrit as well as thiol, SOD, and CAT activities in serum and liver tissue were significantly reduced, but serum nitric oxide, MDA, total cholesterol, triglycerides, low-density lipoproteins levels, and liver enzymes were increased in the CP group compared to the control group (p<۰.۰۵ to p<۰.۰۰۱). Administering M. sativa extract (۴۰۰ mg/kg) significantly enhanced platelet count, and SOD and CAT activities and inhibited all of the CP toxic effects, while dexamethasone improved platelet count and oxidative stress markers compared to the CP group (p<۰.۰۵ to p<۰.۰۰۱).Conclusion: The extract of M. sativa (۴۰۰ mg/kg) showed therapeutic effects against the CP-induced myelosuppression and thrombocytopenia and improved oxidative stress markers which were comparable to the effect of dexamethasone.

Keywords:

Cyclophosphamide , Medicago sativa , Myelosuppression , Thrombocytopenia , Oxidative stress