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PubMedDate not supplied

Renal toxicity induced by folic acid is associated with the enhancement of male reproductive toxicity of di(n-butyl)phthalate in rats.

Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.

Animals↗
PubMed2006

Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men?

We evaluated pre- and post-intervention endocrine and semen parameters in a double-blind, placebo-controlled intervention study to investigate the underlying mechanism of increased sperm concentration after folic acid and zinc sulphate intervention. A total of 47 fertile and 40 subfertile males participated in a 26-week intervention study consisting of a daily treatment with folic acid (5 mg/day) and zinc sulphate (66 mg/day), or placebo. Pre- and post-intervention semen parameters, serum folate, zinc, follicle-stimulating hormone (FSH), testosterone and inhibin B concentrations were measured. The results indicated that intervention treatment significantly increased sperm concentration in subfertile males. Other semen and endocrine parameters were not affected by intervention treatment. At baseline, positive correlations were found between serum zinc and sperm concentration, motility and inhibin B. Serum zinc and FSH were inversely correlated. As (already) well known from previous research, inhibin B positively correlated with sperm concentration, motility and morphology, and was inversely correlated with FSH. The latter was positively correlated with testosterone. In addition, testosterone and inhibin B were inversely correlated. After intervention, the correlations with zinc disappeared. We conclude that the increase in sperm concentration after folic acid and zinc sulphate intervention is not the result of alterations in FSH, testosterone or inhibin B concentrations. Although zinc and folate have several effects on spermatogenesis, the underlying mechanisms involved are not clear.

Adult↗
PubMed2004

Effect of folic acid on homocysteine-induced trophoblast apoptosis.

In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.

Apoptosis↗
PubMedDate not supplied

Synthesis of N-acetyl-D-galactosamine and folic acid conjugated ribozymes.

To evaluate potential improvement in tissue specific targeting and cellular uptake of therapeutic ribozymes, we have developed three new phosphoramidite reagents. These reagents can be used in automated solid-phase synthesis to produce oligonucleotide conjugates containing N-acetyl-D-galactosamine (targeting hepatocytes) and folic acid (targeting tumor). N-Acetyl-D-galactosamine was attached through a linker to both 2'-amino-2'-deoxyuridine and D-threoninol scaffolds, and these conjugates were converted to phosphoramidite building blocks. Incorporation of a D-threoninol-based monomer into ribozymes provided multiply labeled ribozyme conjugates. Attachment of the fully protected pteroic acid to the D-threoninol-6-aminocaproyl-L-glutamic acid construct afforded the folic acid conjugate, which was converted into the phosphoramidite and incorporated onto the 5'-end of the ribozyme.

Acetylgalactosamine↗
PubMed2002

[Genetic differences in enzymes of folic acid metabolism in patients with lip-jaw-palate clefts and their relatives].

BACKGROUND: The effectiveness of folic acid supplementation in the periconceptional period for the prevention of cleft lip/cleft lip and palate (CLP) is contradictorily discussed. Genetically determined variants of enzymes of the folic acid metabolism could be part of the key to success or failure of folate supplementation. A mutation of the methylenetetrahydrofolate reductase (MTHFR) gene is suspected to be a risk factor for CLP. METHODS: The blood samples of 66 CLP patients, their 88 relatives (without CLP), and 184 healthy controls were searched by polymerase chain reaction for mutations of MTHFR 677 C:T, MTHFR 1298 A:C and of the arylamine N-acetyltransferase (NAT1) gene [gene type NAT1 degree 4 (wild type) or not]. RESULTS: There was no significant difference in the number of MTHFR gene mutations (for 677 C:T and 1298 A:C) between the three groups (p approximately 0.3), but for the NAT1 genes (p = 0.033). The homozygote mutation was found more than twice as often in CLP patients (10.5%) and their relatives (10.6%) than in the healthy controls (4.35%). DISCUSSION: Our results provide no evidence that the above MTHFR gene mutations are a risk factor for CLP.A NAT1 gene mutation instead could be a risk factor for CLP.

Adolescent↗
PubMed2005

Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine.

BACKGROUND: Carbamazepine is a commonly used anticonvulsant agent; however, it has been linked with various blood cell abnormalities. This study evaluated the effect of low-dose folic acid supplementation on the prevention of carbamazepine-induced hematological derangements in children. METHODS: This randomized clinical trial was conducted in children with epilepsy who received carbamazepine monotherapy. Group 1 received carbamazepine alone, and group 2 received carbamazepine plus folic acid. The two groups were age- and sex-matched. Each group comprised 41 children with epilepsy. Complete blood counts were obtained before starting medication (baseline) and then serially. The patients were followed for at least 1 year. RESULTS: In group 1, 31.4% of the patients developed leukopenia and 17.1% neutropenia, but in group 2, these figures were 14.6 and 9.8% (P = 0.067 and P = 0.331, respectively). At the end of the first year of follow up, white blood cell and polymorphonuclear cell counts were significantly higher in group 2 (P = 0.007 and P = 0.001, respectively). Hemoglobin concentration dropped in group 1, but rose slightly in group 2; these changes were significant. Platelet, lymphocyte, and monocyte counts and changes in serial blood tests did not differ significantly between the two groups. CONCLUSIONS: Folic acid is a safe drug that can reduce the development of some blood cell abnormalities linked to carbamazepine. It has a favorable effect on preventing the leukopenia and drop in hemoglobin observed in patients receiving carbamazepine, but its exact effect and the optimal dose required to enhance its benefits require further investigation.

Adolescent↗
PubMed1977

Effect of folic acid deficiency on pregnant rats and their offspring.

Two groups of 63-day-old female Wistar rats were fed a folic acid deficient diet, based on 20% of vitamin-free casein and containing 1% of succinylsulfathiazole, for 5 weeks (group A) and 9 weeks (group B) before being bred, and the same diet was continued through pregnancy and lactation. Three out of eleven (21.3%) and three out of seven (42.9%) rats in groups A and B, respectively, resorbed completely, while no control rat resorbed. No pups from group B survived to weaning. Both groups (A and B) showed depressed feed consumption (although the effect in group A rats was small) and weight gains and increased formiminoglutamic acid excretion in the urine during gestation, and low serum folic acid by the end of lactation. A study of blood components in group A rats revealed leucopenia, granulocytopenia, and increased reticulocyte count. While no congenital deformities were observed in pups from deficient dams, group A and group B dams in contrast to controls produced smaller sized litters with lower birth weights and poor survival rate. Surviving pups from group A dams had decreased weaning weights with significantly lower brain weights and brain DNA per gram of tissue.

Animals↗
PubMed1980

[Mathematical description and study of the folic acid cycle reactions].

A general description of the folic acid cycle and associate reactions of thymidilate, purines, methionine and serine biosyntheses is presented as a system of differential equations. The concrete models of this reaction complex as well as methotrexate transport into the leukemia L 1210 and Ehrlich ascite tumour cells and the dynamic inhibition of the target enzyme--dihydrofolate reductase--by methotrexate have been described and investigated. The adequacy of mathematical models to the experimental data has been demonstrated.

Animals↗
PubMed2002

The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery.

The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs. Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined. Given that structure-based drug design strategies are now widely employed, these recent developments have prompted a re-evaluation of the potential of each of the enzymes in the pathway as a target for development of specific inhibitors. Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention.

Animals↗
PubMed1981

Folic acid absorption test in various clinical conditions.

The folic acid absorption test (FAAT) has carried out in 18 normal control subjects; 8 patients with proven atrophy of the jejunal mucosa; 7 patients with gastric ulcus; 17 patients with reactive hypoglycemia; 13 patients with diabetes mellitus, and, finally, 9 epileptic patients treated with diphenylhydantoin (DPH). The most striking fact in this study is the difference between the FAAT in normal subjects versus patients with atrophy of the jejunal mucosa, reactive hypoglycemia and DPH consumption. On the other hand there were no significant differences in folate absorption between controls and diabetic patients.

Adult↗
PubMed2006

Biochemical study on the protective role of folic acid in rabbits treated with chromium (VI).

Deleterious effects of chromium (VI) compounds are diversified affecting almost all the organ systems in a wide variety of animals. Therefore, the present study was carried out to determine the effectiveness of folic acid (FA) in alleviating the toxicity of chromium (VI) on certain biochemical parameters, lipid peroxidation, and enzyme activities of male New Zealand white rabbits. Six rabbits per group were assigned to one of four treatment groups: 0 mg FA and 0 mg Cr(VI)/kg BW (control); 8.3 microg FA/kg BW; 5 mg Cr(VI)/kg BW; 5 mg Cr(VI) plus 8.3 microg FA/kg BW, respectively. Rabbits were orally administered their respective doses every day for 10 weeks. Results obtained showed that Cr(VI) significantly (P < 0.05) increased the levels of free radicals and the activity of glutathione S-transferase (GST), and decreased the content of sulfhydryl groups (SH groups) in liver, testes, brain, kidney, and lung. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP), and lactate dehydrogenase (LDH) were significantly decreased in liver and testes due to Cr(VI) administration. Also, AlP and AcP activities were significantly decreased in kidney and lung. The activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma. Contrariwise, the activities of AST and ALT were significantly increased in plasma, while AlP and AcP decreased. Chromium (VI) treatment caused a significant decrease in plasma total protein (TP) and globulin, and increased total lipids (TL), cholesterol, glucose, urea, creatinine, and bilirubin concentrations. Folic acid alone significantly decreased the levels of free radicals in liver, brain, and kidney, and increased the content of SH-group. The activities of AST, ALT, and LDH in liver; AST, ALT, AlP, AcP, and LDH in testes; AcP in kidney; AlP and AcP in lung, and LDH in brain were significantly increased. Plasma TP and albumin were increased, while urea and creatinine were decreased. The presence of FA with Cr(VI) restored the changes in enzyme activities and biochemical parameters. In conclusion, folic acid could be effective in the protection of chromium-induced toxicity.

Administration, Oral↗
PubMed1995

Folic acid prescription in pregnancy.

We resolved to prescribe folic acid supplements for all women who attended this practice during the first twelve weeks of pregnancy. Six months after this decision a prescription was recorded in only 13% of cases: this compared with 18% during the two months immediately following the decision. It was resolved to improve this performance and observations six months later revealed a prescription recorded in 63% of cases. Subsequently a new form for recording an antenatal consultation was devised and six months after its implementation, 100% recording of folate prescription for appropriate cases was observed. It was concluded that these simple audit exercises prompted changes in practice which helped to improve standards of patient care.

Adolescent↗
PubMed1983

Changes in muscarinic binding in distant brain regions showing neuronal losses after folic acid injections into the substantia innominata.

Injection of folic acid (FA) into the nucleus substantia innominata (NSI) was found to decrease [3H]quinuclidinyl benzilate ([3H]QNB) binding in the frontal cortex, pyriform cortex, amygdala, and the NSI itself without changing the KD. Binding in the thalamus, caudate nucleus, hippocampus, and substantia nigra was not affected. [3H]Flunitrazepam binding was unchanged in all eight regions studied. Previous work indicates FA injections into the NSI produce epileptiform activity and cause loss of GABAergic and possibly other neurons in the frontal and pyriform cortices, the amygdala, and thalamus. The reductions of [3H]QNB binding in the first three of these regions are interpreted as indicating that many of the neurons lost are cholinoceptive, a finding that supports the previous hypothesis that activation of cholinergic projections from the NSI is an important part of the mechanism of cell loss in these regions.

Animals↗
PubMed2005

Effect of baking process on added folic acid and endogenous folates stability in wheat and rye breads.

In Poland bread as a staple food both made from wheat and rye flour can be a potential product for future fortification with folic acid. The objective of the study was to examine the effect of fermentation and baking on added folic acid and some endogenous folates stability during breadmaking of rye and wheat breads. Breads were produced using the formulation containing enriched flour with 0.2 mg folic acid/100 g product, baker's yeast and additionally ascorbic acid for wheat bread and lactic acid for rye bread. Folates were extracted with Hepes/Ches buffer (pH = 7.85) followed by destruction of matrix by amylase and protease and deconjugation with rat serum conjugase. Affinity chromatography (FBP bovine milk) was used to purify and concentrate samples. The folates were separated by HPLC with C18 column and with a combination of fluorescence and UV detection. For both rye and wheat breads there was a decrease of folic acid from flour to bread stage. The total losses depend on baking process and ranged from 12 to 21%. Some changes in the level of different native folate forms during the stage of baking process were also observed.

Bread↗
PubMed2006

Health care provider knowledge and practices regarding folic acid, United States, 2002-2003.

OBJECTIVE: To assess health care providers (HCP) knowledge and practices regarding folic acid (FA) use for neural tube defect (NTD) prevention. METHODS: Two identical surveys were conducted among 611 obstetricians/gynecologists (OB/GYNs) and family/general physicians (FAM/GENs) (2002), and 500 physician assistants (PAs), nurse practitioners (NPs), certified nurse midwives (CNMs), and registered nurses (2003) to ascertain knowledge and practices regarding FA. For analysis, T-tests, univariate and multivariate logistic regression modeling were used. RESULTS: Universally, providers knew that FA prevents birth defects. Over 88% knew when a woman should start taking folic acid for the prevention of NTDs; and over 85% knew FA supplementation beyond what is available in the diet is necessary. However, only half knew that 50% of all pregnancies in the United States are unplanned. Women heard information about multivitamins or FA most often during well woman visits in obstetrical/gynecology (ob/gyn) practice settings (65%), and about 50% of the time during well woman visits in family/general (fam/gen) practice settings and 50% of the time at gynecology visits (both settings). Among all providers, 42% did not know the correct FA dosage (400 mug daily). HCPs taking multivitamins were more than twice as likely to recommend multivitamins to their patients (Odds Ratio [OR] 2.27 95%, Confidence Interval [CI] 1.75-2.94). HCPs with lower income clients (OR 1.49, CI 1.22-1.81) and HCPs with practices having more than 10% minorities (OR 1.46, CI 1.11-1.92) were more likely to recommend supplements. NPs in ob/gyn settings were most likely and FAM/GENs were least likely to recommend supplements (OR 3.06, CL 1.36-6.90 and OR 0.64, CL 0.45-0.90 respectively). CONCLUSIONS: Knowledge about birth defects and the necessity of supplemental FA was high. Increasing knowledge about unintended pregnancy rates and correct dosages of FA is needed. The strongest predictor for recommending the use of FA supplements was whether the provider took a multivitamin.

Attitude of Health Personnel↗
PubMed2003

Plasma reduced folates, reproductive performance, and conceptus development in sows in response to supplementation with oxidized and reduced sources of folic acid.

The study was conducted to determine the response of sows to oxidized and reduced forms of supplemental folic acid in the diet. Gilts were mated and fed a standard corn-soybean meal diet with no supplemental folic acid. On d 105 of gestation, gilts were randomly assigned to one of four dietary treatments for the remainder of the study. Treatments were: 1) diet with no supplemental folate (control), 2) diet with 2.1 ppm (calculated) of added folate supplied by a synthetic pteroylmonoglutamate form (MG), 3) diet with 2.1 ppm (calculated) of added folate supplied by N5-formyl-5,6,7,8-tetrahydrofolic acid (THFA), or 4) a commercial bacterial cell powder source (Aj-PG) rich in reduced folates. Blood samples for high-performance liquid chromotography determination of reduced plasma folates were collected from gilts on d 105 of gestation, at weaning, at mating, and when the females were slaughtered on d 45 after mating for the second parity. There were 19, 18, 18, and 22 sows for the control, MG, THFA, and Aj-PG treatments, respectively. Supplementing folacin just before farrowing and during lactation had no effect on sow and litter performance during parity 1 (P > 0.10). Live fetuses at d 45 of gestation in Parity 2 were 10.06, 12.23, 10.87, and 11.07 for the control, MG, THFA, and Aj-PG treatments, respectively, and did not differ (P > 0.10). Fetal survival and placental size and protein content were generally unaffected by folate treatment. Concentration of reduced folates in sow plasma was 13.50, 13.58, 22.50, and 17.79 nM at weaning and 12.55, 19.29, 18.96, and 21.88 nM at mating for the control, MG, THFA, and Aj-PG treatments, respectively, with the THFA treatment elevated above the controls at weaning (P < 0.05) and the Aj-PG treatment greater than controls at mating (P < 0.05). At weaning, the reduced sources of supplemental folate (THFA and Aj-PG) were more effective in elevating plasma reduced folates than the oxidized folate supplement (MG; P < 0.05). Nonetheless, folate supplementation did not significantly improve sow reproductive performance in the subsequent parity, and there was no indication that reduced folate sources were superior to the oxidized pteroylmonoglutamate form as folate supplements for sows.

Administration, Oral↗
PubMed1984

Combination of anticancer agents with folic acid in the treatment of murine leukaemia P388.

Folic acid (FA) was combined with anticancer agents such as (i) antimetabolites like methotrexate (MTX), 5-fluorouracil (5-FU), arabinosyl cytosine (Ara-C) and 6-mercaptopurine (6-MP); (ii) plant-derived mitotic inhibitor, vincristine (VCR), and (iii) an antibiotic, mitomycin C (Mit-C). This combination modality was used for the treatment of P388 lymphocytic leukaemia. Large doses of FA were administered to the tumour-bearing mice either prior to or simultaneously with different anticancer agents. Pre-treatment with FA significantly improved the therapeutic efficacy of 5-FU, Ara-C and Mit-C; while MTX was more effective when given simultaneously with FA. The efficacy of 6-MP and VCR was not enhanced by FA when tested similarly. Large doses of FA can potentiate the activity of certain anticancer agents when administered to P388-bearing mice at critical times that vary according to the particular drug used.

Animals↗
PubMed2005

[Effect of the supplementation of vitamins B12, B6 and folic acid on homocysteine and plasmatic lipids in patients with hyperlipoproteinemic secondary type IV].

The cases of hyperlipoproteinemic secondary type IV are manifested by elevation of triglycerides, with normal or high cholesterol and lightly high homocysteine. The effect of vitamins B12, B6 and folic acid, on homocysteine and lipids, in 24 male patients, 35-68 years, with hiperlipoproteinemia secondary type IV with myocardial isquemic, and without previous treatment of hipolipemiant, was investigated. The patients were supplemented with therapeutic doses tablets of vitamin B12, 500 (microg/day); B6, (600 mg/day) and folic acid (20 mg/ day), during 120 days. Homocysteine, triglycerides, total and fractional cholesterol, at (basal), 30, 60, 90 and 120 days, were determined. Descriptive statistical analyses were applied, coefficient of correlation of Pearson and proves of "t", with a p < 0.005; the data were processed by statistical program SPSS version 8.0. The results showed a decrease in the levels of homocysteine from basal 17.1 +/- 0.7 micromol/L to 13.18 +/- 0.83 micromol/L, at the end of experimental period. The triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) showed a reduction of (21.8 mg/dl; 8.5 mg/dl; 5.87 mg/dl; respectively) for every pmol/L of reduced homocysteine, with (p < 0.001) for triglycerides. High density lipoprotein (HDL) increased 1.1 mg/dl and coronary risk descent in 24%. We concluded that therapeutic doses of vitamins B12, B6 and folic acid, may is effective in decreased plasmatic homocysteine levels and lipids, mainly triglycerides, with a reduction of coronary risk, to these type of patients, with not collateral effects of neuropathy

Adult↗