Oral exposure to the anti-pyridoxine compound 1-amino D-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B6 deficient rats.

Pyridoxal 5'-phosphate (PLP; a B6 vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to cysteine. While overt vitamin B6 deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B6 deficiency and a study was conducted to examine the in vivo effect of 1-amino D-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B6 deficient rats. Male weaning rats received a semi-purified diet containing either 7 mg/kg (control; CD) or 0.7 mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10 mg/kg diet for 5 weeks. Perturbations in vitamin B6 biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine ß-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B6 deficient.

Identification, characterization, and quantification of an anti-pyridoxine factor from flaxseed using ultrahigh-performance liquid chromatography-mass spectrometry.

In the present study, the anti-pyridoxine compounds linatine (1-[(n-γ-L-glutamyl)amino]-D-proline) and 1-amino-D-proline (1ADP) were quantified following extraction from defatted flaxseed using aqueous isopropanol as a solvent, with extraction variables including time, temperature, and the solid/solvent ratio. Both linatine and 1ADP were identified, characterized, and quantified via UPLC/ESI-MS using authentic standards. To optimize the extraction conditions for these anti-pyridoxine compounds, a response surface methodology was applied using a second-order polynomial to describe the experimental data. The predicted model for the optimal extraction was significant (P < 0.05) with a R(2) of 0.82. A varietal analysis showed that the amount of anti-pyridoxine present in flaxseed ranged from 177 to 437 µg 1ADPE/g of whole seed. The current study establishes the content of specific anti-pyridoxine factors in flaxseed and positions the data for use in subsequent risk assessment modeling.

High-dosage pyridoxine-induced auditory neuropathy and protection with coffee in mice.

Auditory neuropathy (AN) is a hearing disorder characterized by an abnormal auditory brainstem response (ABR). This study examined experimental AN model induced in mice following increased dosages of pyridoxine. Induced AN was examined for < or =10 weeks following the last pyridoxine treatment. To assess AN, we evaluated the ABR, auditory middle latency response (AMLR), otoacoustic emission (OAE), and histochemical morphology of the auditory nerve. Pyridoxine-treated mice exhibited an increase in the hearing threshold shift and delayed latency of both ABR and AMLR in proportion to pyridoxine dosage. Additionally, the extent of auditory nerve fiber loss increased in a dose-dependent manner following pyridoxine intoxication. Coffee or trigonelline treatment ameliorated the hearing threshold shift, delayed latency of the auditory evoked potential, and improved sensory fiber loss induced by pyridoxine intoxication. The present findings demonstrate that high-dose pyridoxine administration can be used to produce a new mouse model for AN, and coffee or trigonelline as a main active compound of coffee extract can potentially facilitate recovery from pyridoxine-induced auditory neuropathy.

Thoracic spine compression fracture during isoniazid-induced seizures: case report.

We report here an 11-year-old previously healthy girl with isoniazid intoxication who sustained a seizure-induced thoracic compression fracture. The following might be the first such case reported in the medical literature. Isoniazid toxicity should be suspected in any patient who comes to the emergency department with refractory seizures and metabolic acidosis. Forceful muscle contractions during a convulsive seizure can result in vertebral compression fracture, especially in the midthoracic region. A complaint of back pain after isoniazid-induced seizures in patients raises a strong suspicion of vertebral fracture and should be evaluated radiologically.

Effects of dietary pyridoxine on immune responses in abalone, Haliotis discus hannai Ino.

A feeding experiment was conducted to investigate the effects of dietary pyridoxine (PN) on the immune responses of abalone, Haliotis discus hannai Ino. Purified diets supplemented with 0, 40, 800 mg PN kg(-1) or 80 mg kg(-1) of 4-deoxypyridoxine (PN antagonist) were fed to adult abalone (initial weight 45.77 +/- 0.25 g; initial shell length 68.02 +/- 0.78 mm) for 90 days. The air-dried brown kelp, Laminaria japonica, was used as a control diet. Each diet was fed to three replicate groups of abalone in a recirculation system using a completely randomised design. The results showed that weight gain ratio (WGR) of the abalone generally increased with the level of dietary PN supplementation though no significant differences were found among the treatments (P > 0.05). Phagocytic and phenoloxidase activities were significantly higher in abalone fed diets supplemented with 800 mg PN kg(-1) than those fed the PN-free diet or the one with 4-deoxypyridoxine (P < 0.05). Agglutination titre and respiratory burst activity were significantly higher in abalone fed diets supplemented with 40 mg PN kg(-1) than those fed the PN-free diet or the one with 4-deoxypyridoxine (P < 0.05). There were no significant differences in immunological characteristics between the abalone fed the diet containing 40 mg PN kg(-1) and those fed the diet containing 800 mg PN kg(-1) (P > 0.05). L. japonica resulted in significantly lower agglutination titre, respiratory burst and phagocytic activities than the artificial diets supplemented with 40 or 800 mg PN kg(-1) (P < 0.05). Total haemocyte count (THC), serum protein concentration, and the activities of lysozyme and acid phosphatase were not significantly affected by the dietary treatments (P > 0.05). These results demonstrate that dietary deficiency of pyridoxine suppresses the immune functions in H. discus hannai, and further investigations are needed to optimise the dietary level of this vitamin for maintaining the best immune responses in abalone.

[Antiamnesic effect of cytoflavin and neuronol in rats with ischemic impairment of cerebral circulation]. / Antiamnesticheskii éffect tsitoflavina i neironola pri ishemicheskom narushenii krovoobrashcheniia u krys.

The antiamnesic action of the new complex preparations cytoflavin and neuronol was studied in rats with a cerebral ischemia model, tested for the passive avoidance conditioned reflex. The neuroprotector effect of drugs was determined by morphological methods. Both cytoflavin and neuronol reduced neuronal damage in the pyramidal layer of the hippocampus and prevented the development of amnesia during the entire period of cerebral ischemia (3-21 days). Both drugs also improved horizontal locomotor activity and emotional reactions of animals in the open field test.

Vitamin B6 antagonists alter the function and ultrastructure of mice endothelial cells.

Vitamin B6, is necessary for normal membrane function and stability. Here we studied both the function and ultrastructure of aortic and arterial endothelial cells (ECs) in vitamin B6 deficient mice induced by vitamin B6 antagonists, 4-deoxypyridoxine x HCl (dPN x HCl), and isonicotinylhydrazide (INH). Mice were fed with normal laboratory chow and divided into three groups according to their drinking water. Mice in group I had distilled water and served as a control; group II had 0.1 mg dPN x HCl/mL H2O; and group III had 0.4 mg INH/mL H2O. After 5 mo, plasma concentrations of B6 vitamers pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) were analyzed by HPLC. With the arachidonic acid (AA) as a precursor, prostacyclin (PGI2) production from ECs assayed by thin-layer chromatography (TLC) was used as an indicator of endothelial function. Aorta and arteriole from foot pad were removed, stained with osmium tetraoxide, and examined under transmission electron microscopy (TEM) to study the ultrastructure of ECs. The results showed that plasma concentrations of PLP, PL, and total B6 were the lowest for mice fed with INH. followed by that with dPN x HCl, compared with that of control. PGI2 production was paralleled with the plasma vitamin B6 status, with the lowest level for INH, followed by the dPN-treated group. Abnormalities in the ultrastructure of ECs were found in both dPN x HCl and INH groups, including cells detached from underlying elastic tissue, with prominent pinocytotic vesicles and swelling and/or indistinct cristae of mitochondria. These results suggest that vitamin B6 antagonists induce a deficient status that alters the function and the ultrastructure of ECs detrimental to vascular disease.

Bilobalide prevents reduction of gamma-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus.

We previously reported that bilobalide, a constituent of Ginkgo biloba L. leaves, protected mice against convulsions induced by 4-O-methylpyridoxine (MPN). To elucidate the mechanism of the anticonvulsant activity of bilobalide, this study examined the effect of bilobalide on MPN-induced changes in the levels of gamma-aminobutyric acid (GABA) and glutamate, and in the activity of glutamic acid decarboxylase (GAD) in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels and GAD activity in the hippocampus and cerebral cortex were significantly enhanced by bilobalide treatment (30 mg/kg, p.o., for 4 days) alone. MPN significantly decreased GABA levels and GAD activity in the three brain regions tested compared with those in the control. Pretreatment with bilobalide effectively suppressed the MPN-induced reduction in GABA levels and GAD activity in the hippocampus and cerebral cortex. On the other hand, there were no significant differences in the glutamate levels in the three regions despite various treatments. These results suggested that bilobalide prevents MPN-induced reduction in GABA levels through potentiation by bilobalide of GAD activity, and this effect of bilobalide contributes to its anticonvulsant effect against MPN-induced convulsions.

Pyridoxine-5'-beta--glucoside exhibits incomplete bioavailability as a source of vitamin B-6 and partially inhibits the utilization of co-ingested pyridoxine in humans.

This research was conducted to investigate 1) the bioavailability of pyridoxine-5'-beta-D-glucoside (PN-glucoside) relative to that of pyridoxine (PN) in human subjects, and 2) the competitive effect of PN-glucoside on the metabolism of co-ingested PN. To evaluate PN-glucoside bioavailability, the subjects were administered a single oral dose of either deuterium-labeled ([2H2]) PN (Trial 1) or [2H2] PN-glucoside (Trial 2), and the urinary excretion rates of labeled 4-pyridoxic acid (4PA) were measured. The [2H2]4PA derived from [2H2] PN or [2H2]PN-glucoside was excreted mainly in the first 8 h after the dose. Excretion of [2H2]4PA during the 48-h postdose period indicated that the bioavailability of PN-glucoside was approximately 50% relative to PN, which is consistent with our previous report of 58% bioavailability determined using a different protocol and fewer subjects. To assess the effects of PN-glucoside on PN utilization, the subjects were administered different ratios of nonlabeled PN-glucoside with [2H2]PN in Trials 3 and 4. Comparing Trial 1 with Trials 3 and 4, the quantity of nonlabeled PN-glucoside, as a fraction of total vitamin B-6 administered, ranged from 0 to 40% (on the basis of pyridoxine equivalents), with a constant dose of [2H2]PN in each. In these trials, the rate but not the total extent of the excretion of [2H2]4PA derived from [2H2]PN was inversely related to the proportion of co-ingested nonlabeled PN-glucoside. Thus, antagonistic effects of PN-glucoside on PN metabolism do occur in humans, although the effect is less pronounced than that seen previously in rats. Such interactive effects must be considered in evaluating the net bioavailability of dietary forms of vitamin B-6.

4-Deoxypyridoxine inhibits chronic granuloma formation induced by potassium permanganate in vivo.

4-Deoxypyridoxine (4-DPD) is a potent antagonist of Vitamin B6 coenzyme which inhibits IL-1, lymphocyte proliferation and has demonstrated that tolerance to skin grafts can be induced by administering splenic cells to pyridoxine-deficient mice. Chronic inflammation induced by dorsal injections of 200 microliters of a 1:40 saturated crystal solution of potassium permanganate (KMnO4) in mice treated or untreated with 4-DPD (400 micrograms/dose), has been investigated. After 7 days all mice developed a subcutaneous granulomatous tissue indicative of a chronic inflammatory response, at the site of injection. KMnO4-treated mice injected intraperitoneally with 4-DPD (400 micrograms/dose) on 5 consecutive days (the first at the same time of induction of the granuloma) show a significant decrease in size and weight of granuloma when compared to mice not treated with 4-DPD (Controls). In addition, in all mice treated with 4-DPD there was a strong inhibition of TNF alpha in serum (P < 0.01) and in supernatant fluids (P < 0.05) from minced granuloma, while IL-6 was inhibited in the supernatant fluids (P < 0.05) of minced granulomas but was not detected in the serum of treated and untreated mice. In this study we show for the first time the antiinflammatory effect of 4-DPD on chronic inflammation and the inhibitory effect of TNF and IL-6 generation in supernatant fluids from minced granulomas.

Effect of combination of deoxypyridoxine with known anti-proliferative or immunosuppressive agents on lymphocyte serine hydroxymethyltransferase.

Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme is very low. Under the influence of mitogenic stimuli serine hydroxymethyltransferase activity is induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine (dB6), a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of SHMT. Separate addition in the cultures of four anti-proliferative (AP) and immunosuppressive (IMS) agents, namely actinomycin, cytarabine, asparaginase and cyclosporine, led to the following observations. (1) The AP and IMS agents produce a decrease in the mitogen-induced activity of SHMT. The higher the concentration of the AP/IMS compound, the greater the decrease of enzymatic activity. (2) When a AP/IMS agent is combined with dB6 its effect on SHMT is considerably greater. (3) Ineffective concentrations of AP/IMS agents become effective when combined with dB6. (4) The observed changes in SHMT activity are not, as one would expect, the same in the case of all four drugs. (5) The combination makes it possible to use much smaller doses of these agents with much better results, at least as far as the decrease of enzymic activity is concerned. This is very promising for clinical use of AP agents in cancer chemotherapy and IMS agents in transplantation especially of the heart and lungs, because combining these compounds with dB6 will make possible to use smaller doses over a longer period of time with greater effectiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Pyridoxine-5'-beta-D-glucoside competitively inhibits uptake of vitamin B-6 into isolated rat liver cells.

Uptake of pyridoxine-5'-beta-D-glucoside by freshly isolated rat liver cells was studied at a concentration (0.5 mumol/L) approximating the physiological range of vitamin B-6 by using a membrane filtration method. Unlabeled pyridoxine glucoside was found to competitively inhibit the uptake of [4'-3H]pyridoxine but have no detectable effect on the uptake of D-[1-3H]glucose by hepatocytes. The uptake of [3H]pyridoxine glucoside by isolated rat liver cells was very similar to the uptake of [3H]pyridoxine with Kt = 13.8 mumol/L (6.3 mumol/L for pyridoxine) and Vmax = 82 pmol/(10(6) cells.min) [28 pmol/(10(6) cells.min for pyridoxine)]. The results of this study indicate that pyridoxine glucoside uses the same transport system as does pyridoxine. Upon entry to the cell, pyridoxine glucoside undergoes hydrolysis to release pyridoxine, which is the rate-limiting step in metabolism of this beta-glucoside.

Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol.

The aims of this study were to define normal human placental transport of pyridoxal, an important form of vitamin B6 in pregnancy, and to determine the effect of short-term alcohol on this process. Our studies used the isolated single cotyledon from the term placenta. Pyridoxal crossed the human placenta readily in both directions, but the transfer was a little less than half that of antipyrine and was significantly greater in the direction of the fetus. Pyridoxine appeared to have a similar clearance from the maternal compartment as pyridoxal, but transport of intact pyridoxal 5'-phosphate was much smaller. There was no saturable transfer of pyridoxal, and it was not transferred from the maternal to fetal compartments against a concentration gradient. Placental concentration of pyridoxal exceeded both maternal and fetal perfusate pyridoxal concentrations, but this concentration was equal for both perfusion directions. These composite data are most suggestive of passive transport of pyridoxal across the placenta, binding of the vitamin in the placenta as an explanation for its concentration there, and greater phosphorylation of pyridoxal in the placenta when the compound is transferred in the fetal direction, possibly displacing pyridoxal from its binding sites and permitting its greater release into the fetal compartment. Alcohol, 400-250 mg/dl over 2.5 h, inhibited the transport of pyridoxal from the maternal to fetal compartments by approximately 42% (P = 0.03) and resulted in a lower transfer of pyridoxal 5'-phosphate into the fetal perfusate (P = 0.02).

Effect of pyridoxine deficiency on immunological phenomena.

Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme was very low. Under the influence of mitogenic stimuli serine hydroxymethyl-transferase activity was induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine, a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of serine hydroxymethyltransferase. Thus deoxypyridoxine exerts its effects not only at the level of the enzyme itself by antagonizing the coenzyme but also at the level of its biosynthesis. Synchronous addition of vitamin B6 with deoxypyridoxine effectively reverses the inhibitory effects. The T helper cells of the lymphocyte culture are very sensitive to deoxypyridoxine action in contrast to T suppressor cells. The effect of phytohaemagglutinin or concanavalin A on the production of interleukin-1b, interleukin-2 and interleukin-2 receptors is profoundly affected by deoxypyridoxine. These results give a deeper insight of the mechanisms by which pyridoxine deficiency causes significant reduction of humoral and cellular immune responses to antigenic stimuli. On the basis of the data of this report a detailed illustration of the events that follow the T cell activation is presented. From this investigation the enzyme serine hydroxymethyltransferase emerges as a key element in the processes of immune responses and cell proliferation. Based on this finding we advance the following two propositions for possible future medical application: (i) combination of deoxypyridoxine with immunosuppressive drugs in case of immunosuppressive therapy or organ transplantation. (ii) the enzyme presents an excellent target for chemotherapy and therefore development of special agents directed against its apoprotein may prove to be a very valuable medical tool.

[Mechanism of vitamin B6 regulation of acetylcholine-induced currents in mollusk neurons: pre- and postsynaptic effects]. / Mekhanizm reguliatsii vitaminom B6 atsetilkholinindutsiruemykh tokov v neironakh molliuska: pre- i postsinapticheskie éffekty.

Vitamin B6 has been studied for the mechanism of its effect on acetylcholine-induced sodium-potassium and chloride currents in E16 neuron of isolated brain of the snail Helix pomatia. The results indicate that the effect of vitamin B6 on acetylcholine-induced currents in postsynaptic neuron E16 is mediated via changes in gamma-aminobutyric acid (GABA) release from a presynaptic neuron and subsequent GABA-induced and cAMP-dependent processes in E16 neuron. It is suggested that effects of vitamin and antivitamin B6 on axons of a presynaptic neuron or neurons may be connected with regulation of GABA synthesis from glutamate catalyzed by the pyridoxal-phosphate-containing enzyme.

Vitamin B6 in clinical neurology.

Many conditions in clinical neurology may be responsive to pyridoxine as a therapeutic agent. The current difficulty is in trying to isolate the conditions that are most likely to respond. Treating seizures is a major part of a neurologic practice. Our current therapeutic agents are only partially successful and limited by multiple side effects. One problem is that patients often have to take these agents for an entire lifetime, further raising the risk of toxicity. If pyridoxine supplementation can improve the efficacy of currently used medications, it will be gladly accepted into our therapeutic arsenal. Headache, chronic pain, and depression all appear to run together in many of our patients. The observations that serotonin deficiency is a common thread between them and that pyridoxine can raise serotonin levels open a wide range of therapeutic options. Small studies have been carried out with mixed success. Comparison with amitriptyline in the treatment of headache appears to show about equal efficacy, although side effects would be expected to be more of a problem with the amitriptyline. Behavioral disorders are relatively common and continue to be a major problem, disrupting the lives of the patients and their families. Current treatments are not acceptable to most people because of the risk of side effects with long-term usage. If, as Dr. Feingold suggests, many of these problems are caused by "toxic" exposures to chemicals that are pyridoxine antagonists, supplementation at early ages may reduce the incidence of hyperactivity and aggressive behavior. This raises the question of safety. Is pyridoxine safe for long-term use in large segments of the population, including children? The studies on children with Down's syndrome and autism, utilizing much higher doses than are used for other therapeutic purposes, seem to indicate relative safety if carefully monitored. Studies involving large population groups with carpal tunnel syndrome, all adults, using 100-150 mg/day have shown minimal or no toxicity in five- to 10-year studies. Women self-medicating for PMS taking 500 to 5000 mg/day have shown peripheral neuropathy within one to three years. It would appear from this retrospective analysis that pyridoxine is safe at doses of 100 mg/day or less in adults. In children there is not enough data to make any sort of suggestion. Because the major neurologic complication is a peripheral neuropathy and the causes of this condition are myriad, pyridoxine may cause neuropathy only in patients with a pre-existing susceptibility to this condition.

Pyridoxine deficiency and antagonism produce increased ground substance viscosity with resulting seborrheic dermatitis and increased tumor resistance.

Pyridoxine deficiency and 4'-deoxypyridoxine produce acrodynia in rats and seborrheic dermatitis in man. They also produce tumor inhibition in man and animals. Pyridoxine is extensively involved in metabolism and its relationship to the inhibitor 4'-deoxypyridoxine is complex. Pyridoxine deficiency and antagonism increases ground substance viscosity. This increase the inflammatory reactivity of the skin to produce acrodynia in rats and seborrheic dermatitis in man. The increase in ground substance viscosity would explain the increased resistance to tumors in man and animals. Pyridoxine is important in protein metabolism. The protein moiety of glycosaminoglycans in ground substance is small but plays a major role in tissue viscosity. Pyridoxine deficiency or antagonism by itself does not offer a definitive answer for tumors. Combined with substances that stimulate fibroblast or glycosaminoglycans production it may have a significant additive effect.

Intracellular predominance of the pyridoxal 5'-phosphate form of aspartate aminotransferase in Escherichia coli B and reversible transformation of this form by extracellular substances.

The intracellular proportion of the pyridoxal 5'-phosphate form of aspartate aminotransferase to the total enzyme in E. coli B cells was determined by a newly devised method, dependent on selective inactivation of the intracellular pyridoxal 5'-phosphate form of the enzyme by extracellularly added sodium borohydride. A large portion (80-99%) of the intracellular aspartate aminotransferase was in pyridoxal 5'-phosphate form in both natural and synthetic medium-grown bacterial cells. The intracellular predominancy of pyridoxal 5'-phosphate did not vary during the growth of bacteria and during incubation of bacterial cells in various kinds of buffers with different pH values. In contrast, the saturation levels generally used to describe in vivo the proportions of the apo and holo vitamin B6-dependent enzymes did not reflect the intracellular amount of the pyridoxal 5'-phosphate (holo) form of aspartate aminotransferase probably because the intracellular pyridoxal 5'-phosphate form was changed to an apo form by the disruption of bacterial cells for preparing crude extract. Various extracellularly-added vitamin B6 antagonists decreased the intracellular amount of pyridoxal 5'-phosphate without decrease in the total intracellular activity of the enzyme. The modified forms were stable in E. coli B cells and reversed into pyridoxal 5'-phosphate form by incubation of the antagonist-treated cells in the buffer containing pyridoxal. The present results showed that the sodium borohydride reduction method can be used for further analysis of the in vivo interaction of pyridoxal 5'-phosphate and apoaspartate aminotransferase. The fact that about 50% of the intracellular pyridoxal 5'-phosphate form was changed to a modified form without impairment of cell growth in the presence of 4-deoxypyridoxine, and that about 50% of intracellular modified aspartate aminotransferase was reversed to pyridoxal 5'-phosphate by the removal of antagonist followed by incubation suggested that there exists characteristically 2 different fractions of pyridoxal 5'-phosphate forms of aspartate aminotransferase in E. coli cells.

c-Fos mRNA induction under vitamin B6 antagonist-induced seizure.

c-Fos mRNA expression was studied in mouse brain after vitamin B6 antagonist-induced seizure. The vitamin B6 antagonists used were hydrazine, thiosemicarbazide, penicillamine and deoxypyridoxine. Only deoxypyridoxine was effective in increasing c-fos mRNA and c-fos protein expression in nerve cells. The other 3 antagonists had levels of c-fos mRNA below or equal to basal level. The seizure activity induced by several vitamin B6 antagonists resulted in different effects on c-fos gene expression.