Protective effect of the thiol agent WR-2721 against cyclophosphamide-induced cytotoxicity in the mouse erythropoietic system.

: The effect of WR-2721 against cyclophosphamide-induced cytotoxicity was studied using the mouse micronucleus test. Adult male Swiss mice were treated intraperitoneally with a dose of 200 mg/kg or 400 mg/kg b.w. WR-2721, 15 or 30 minutes prior to cyclophosphamide administration, with a dose of 200 mg/kg b.w. The frequency of micronuclei in polychromatic erythrocytes and the number of polychromatic erythrocytes in the peripheral blood were determined 24-hours after CP treatment. In comparison with the controls, in mice injected with cyclophosphamide, the number of micronucleated polychromatic erythrocytes was increased, and the number of polychromatic erythrocytes was decreased. In mice treated with WR-2721 and CP, in relation to those injected with cyclophosphamide alone, the frequency of micronuclei in polychromatic erythrocytes was lower, but the number of polychromatic erythrocytes was found to be greater. The protective effect of WR-2721 against cyclophosphamide-induced clastogenicity and suppressing mitotic activity of the erythropoietic system caused by the alkylating drug was shown. The effect was dependent on the dose of the thiol compound applied and it was more expressive when WR-2721 was given in the higher dose, 400 mg/kg b.w. However, the protection by aminothiol appeared not to depend on the time intervals between WR-2721 and CP administration into mouse organism. The result may be useful for therapeutic application of WR-2721 with cyclophosphamide therapy.