Effect of anticonvulsant drugs on the rate of folate catabolism in mice.

Abstract

A B S T R A C T An increase

Effect of Acute and Chronic Alcohol Ingestion on the Rate of Folate Catabolism and Hepatic Enzyme Induction in Mice

“…In a typical experiment 72% of the dose was excreted over 24 h in the control group; 78% in group A; 76% in group B; 70% in group C. This implies comparable injection and collection techniques (Chantler, Garnett, Parsons & Veall, 1969;Kelly et al, 1979).…”

“…Estimation of these catabolites was performed by alkaline hydrolysis of all p-[ 3H1AB-containing catabolites in the urine to p-[3Hlaminobenzoic acid, which was subsequently extracted by a chemical procedure (Kelly et al, 1979). Radioactivity was estimated as previously described (Kelly et al, 1979).…”

“…We have developed an experimental animal model to determine the rate of folate catabolism in mice by the quantitative estimation of the two urinary catabolites p-aminobenzoylglutamate (pABGlu) and acetamidobenzoylglutamate (ApABGlu) (Kelly, Reed, Weir & Scott, 1979~. Subsequently we demonstrated that the anticonvulsant drug, phenytoin, significantly increased the rate of catabolism whereas administration of phenobarbitone did not (Kelly et al, 1979), implying that microsomal-enzyme induction was not the mechanism for the accelerated folate catabolism. The aim of this study was to investigate the effect of acute and chronic alcohol ingestion on the rate of folate catabolism and microsomal induction.…”

Folate metabolism and neural tube defects: a review

“…This is supported by the relationship between the use of antiepileptic drugs, folate levels and adverse pregnancy outcome, including spontaneous abortions and congenital malformations [44]. Antiepileptic drugs such as phéno barbital, phenytoin and primidone can reduce folate lev els by inhibiting intestinal absorption, or by increasing folate turn-over due to induction of the cytochrome P-450 glucuronyl transferase enzymes [45,46]. The mater nal use o f valproic acid and carbamazepine is considered to increase the risk of spina bifida in particular [47,48], For both antiepileptic drugs, no strong evidence is avail able for the presence of abnormally low serum folate lev els, but several studies report some form of interference with folate metabolism [49,50].…”

“…The natural-occurring folates consist o f a large group o f derivatives derived from the reduc tion and addition to the basic structure. Folates are available in part as small molecules with one to three 40 61 (1995) [39][40][41][42][43][44][45][46][47][48] The stored THF-polyglutamates can be degraded to THF-monoglutamates by intracellular conjugase and released into the circulation. 5-methyl-THF-monoglutamate is the predominant form o f folate in serum and in many tissues.…”