Hematologic Changes in Rat Following Administration of Desoxypyridoxine, Aminopterin, Oxythiamine and 6,7-Dimethyl-9-(2'-acetoxyethyl)isoalloxazine

1. Administration of aminopterin to rats at a level of 100 γ/Kg./day for a 10 day period produced leukopenia which was rapid in onset and led quickly to death, whereas the leukopenia produced by the administration of desoxypyridoxine at the level of 40 mg./Kg./day for a 2 week period or at 100 mg./Kg./day for a 4 week period was not accompanied by toxic effects such as loss of appetite, diarrhea and hemorrhage and was characterized by lymphocytopenia and granulocytosis.

2. The results of combining the administration of aminopterin (70 γ/Kg./ day) with desoxypyridoxine (40 mg./Kg./day) for a 2 week period indicated an additive effect of the two in the production of lymphocytopenia; the granulocytosis resulting from desoxypyridoxine administration was counter-acted by the granulocytopenic effect of aminopterin. Also, the leukopenia produced by the combined administration of aminopterin and desoxypyridoxine was not accompanied by the toxic effects which follow aminopterin administration.

3. Oxythiamine alone or in combination with desoxypyridoxine or aminopterin did not influence the leukocyte count.

4. Administration of aminopterin with 6, 7-dimethyl-9-(2'-acetoxyethyl)isoalloxazine (U-2112) produced marked lymphocytopenia and granulocytopenia accompanied by toxic effects such as loss of appetite, diarrhea and hemorrhage.

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