Pteridines (Sep 1997)
Experimental Study Evaluating the Effect of Combined Methotrexate and Fluorouracil Therapy on Anemia in Mice With L1210 Lymphoid Leukemia
Abstract
Combined methotrexate (MTX) and fluorouracil (FU) has heen used for many years to treat neoplastic diseases. However, clinical and laboratory snldies are still carried out to explain the changes that the therapeutic and toxic effects undergo when MTX and FU are used as a combined therapy. The schedules of combined therapy used so far have either proved not very effective in retrospective assessment, or caused severe tOJ{jc symptoms. Antineoplastic drugs damage the matrix cells of bone mar· row; the effect of commonly used doses more frequently concerns immature forms of blood morphotic elements. Methotrexate belongs to the group of drugs with very potent toxic effect on mOlphotic elements of peripheral blood; the effect of fluorouracil is weaker. Methotrexate causes anemia due to the deficiency of folic acid. For correct metabolism of folic acid, cyanocobaJamin is necessary. With deficiency, or lack of cyanocobalamin, the process is disturbed and a marked decrease of folic acid concentration in erythrocytes occurs. The main circulating and accumulated folate is N 5 -methyltetrahydrofolate which is metabolically inactive itself. In the presented study the morphotic elements were determined iI1 mice inoculated i.p. with LIllO lymphoid leukemic cells. The determinations were carried out on the 14rh day after LIllO inoculation. In untreated animals a decrease of hemoglobin, hematocrit and erythrocyte count values took place as compared with the values observed in healthy mice. 3 schedules of cytostatics administration were used: MTX was administered lh before FU, MTX and FU were adrninistered simultaneously and FU was administered lh before MTX. It has been demonstrated that in mice inoculated with L1210 leukemia anemia was the least pronounced after the combined treatment schedule involving the adrninistration of MTX prior to FU. The indicators of folic acid deficiency in serum and erythrocytes (i.e. NS-methyltetrahydrofolate levels), and cya.-lOcobalamin deficiency in serum in. mic.e with LIllO lymphatic leukemia are aggravated after instituting the combined therapy schedules involving the administration of FU as the first drug, or simultaneous administration of MTX and FU.
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