Pteroylpolyglutamates in liver of phenobarbitone-treated rats

The effects of "acute" phenobarbitone treatment on some aspects of folate metabolism in rat liver, that is total folate activity, protein bound and free folate, and various-length pteroylpolyglutamate amounts, were studied. The administration of two doses of the anticonvulsant drug (8 mg/100 g of body weight), caused a severe depletion in folate pool, free folate and in the percentage of longer-chain polyglutamates, while the amount of protein bound folates was unchanged. Such modifications are more evident in the animals killed at 24 h after the last drug injection rather than in those killed 12 h later. The possible mechanisms by which phenobarbitone might interfere with the synthesis of pteroylpolyglutamates, the actual coenzymic forms of folic acid, are discussed.