Citrus extract modulates genotoxicity induced by cyclophosphamide in mice bone marrow cells

The protective effect of citrus extract was investigated by using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells; liver glutathione (GSH) content was determined against toxicity induced by cyclophosphamide. Mice were orally (gavage) pretreated with solutions of citrus peel extract (Citrus aurantium var. amara) prepared at three different doses (100, 200 and 400 mg kg(-1;) body weight) for 7 consecutive days. Then mice were injected intraperitoneally on the seventh day with cyclophosphamide (50 mg kg(-1)) and after 24 h killed for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow cells. Non-protein thiol levels in liver were estimated in mice injected with citrus extract with or without cyclophosphamide treatment. Administration of citrus extract before cyclophosphamide treatment significantly reduced the frequency of MnPCEs in mice bone marrow compared with the group treated with cyclophosphamide alone (P<0.0001-0.05). Citrus extract at a dose of 400 mg kg(-1) reduced MnPCEs 2.8 fold against genotoxicity induced by cyclophosphamide. Administration of cyclophosphamide depleted the GSH level in liver. Citrus extract showed excellent scavenging effects on 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) at a concentration of 1.6 mg mL(-1). Application of citrus extract 1 h before cyclophosphamide treatment allowed GSH content to reach the normal level. It appeared that citrus extract, particularly flavonoids constituents with antioxidative activity, may return the GSH level to normal in stress conditions and reduces genotoxicity induced by cyclophosphamide in bone marrow cells.