• Journal of Nutrition and Health
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• v.36 no.8
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• pp.801-810
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• 2003

Chronic alcoholism is considered a common cause of malnutrition. Especially, micronutrient deficiency may playa critical role in the incidence of alcoholic liver diseases. This study was conducted to investigate the effect of folate deficiency and ethanol consumption on cholesterol metabolism and the antioxidative system in rats. Plasma concentration of total cholesterol was increased by ethanol administration in folate-fed rats. HDL-cholesterol tended to be higher in the folate-fed group, but it was not significant. The plasma and hepatic levels of malondialdehyde were increased after chronic ethanol feeding, but dietary folate depressed the plasma malondialdehyde content of rats. Ethanol or folate feeding did not significantly change alcohol dehydrogenase activity. But folate feeding increased catalase activity in ethanol-fed rats. There was no significant change in superoxide dismutase activity among the experimental groups. Glutathione peroxidase activity tended to decrease by chronic ethanol feeding, but dietary folate did not affectthe glutathione peroxidase activity of chronic ethanol-fed rats. Glutathionine-S-transferase activity was not affected by ethanol feeding or folate deficiency. The plasma and hepatic levels of retinol decreased after chronic ethanol feeding. The hepatic level of retinol significantly decreased in ethanol-fed rats by folate deficiency. The plasma level of $\alpha$-tocopherol tended to be low in the folate deficient group with ethanol feeding, but there was no difference among the experimental groups in the hepatic level of $\alpha$-tocopherol. These results demonstrate that chronic ethanol consumption changes the plasma cholesterol metabolism and antioxidative system of rats, and optimal folate feeding in ethanol-fed rats exerts protective effects to some extent.

• Proceedings of the KSCN Conference
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• 1999.05a
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• pp.129-129
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• 1999

• Environmental Mutagens and Carcinogens
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• v.23 no.1
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• pp.1-6
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• 2003

The purpose of this study was to evaluate whether the MTHFR variants, folate and vitamin $B_{12}$ deficiencies increase the risk of hyperhomocysteinaemia and adverse pregnancy outcome such as short gestational age or reduced birth weight. Healthy pregnant women (n=136; 24-28 gestational weeks; 20-40 years old), who visited Ewha Womans University Hospital for prenatal care, participated in this study. At the time of delivery, trained nurses recorded the pregnancy outcome from medical chart. We determined maternal MTHFR polymorphisms (C to T subsitution at nucleotide 677) and measured serum homocyteine, vitamin $B_{12}$, and folate concentrations. We compared serum homocysteine level by MTHFR genotype, serum folate and serum vitamin B12 levels using ANOVA. To evaluate the association between serum homocysteine level and pregnancy outcome, we compared the gestational age and birth weight by serum homocysteine levels using multiple regression analysis, adjusting for other potential predictors. Mean level of serum homocysteine was highest among pregnant women of the MTHFR variants with low levels of serum folate and vitamin $B_{12}$. Regarding association with birth outcome, we found the relationship between homocysteine levels and increased gestational age (p=0.03) and reduced birth outcome (p>0.05). Our data demonstrates that serum level of folate and vitamin $B_{12}$ among pregnant women affects significantly serum homocysteine levels, and the genetic polymorphism of MTHFR modulates the relationship between them. However, we did not have conclusive evidence of association between high homocysteine level and adverse pregnancy outcome such as preterm or low birth weight.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.979-983
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• 2003

The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 $\mu$g/mL$.$h for mild renal failure and 4074 $\mu$g/mL$.$h for moderate renal failure) than that in normal rabbits (i.e., 2295 $\mu$g/mL$.$h). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 $h^{-1}$) than that in normal rabbits (i.e., 0.044 $h^{-1}$ ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.

• Journal of Nutrition and Health
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• v.44 no.6
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• pp.498-506
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• 2011

This study examined the relationship among plasma homocysteine, folate, and vitamin $B_{12}$ levels and neurocognitive function in 118 community-dwelling elderly subjects (mean age, $75.1{\pm}6.7$ years). The Mini-Mental State Examination (MMSE-KC) was used to screen and assess neurocognitive function in the participants. Dietary intake data including the use of dietary supplements were obtained using the 24-hour recall method by well-trained interviewers. Plasma folate and vitamin $B_{12}$ concentrations were analyzed by radioimmunoassay, and homocysteine was assessed by a high performance liquid chromatography-fluorescence method. The proportions of participants with suboptimal levels of plasma folate (< 3 ng/mL), vitamin $B_{12}$ (< 221 pmol/mL), and homocysteine (> $15{\mu}mol/L$) were 16.1%, 5.9%, and 21.2%, respectively. A multiple regression analysis showed that plasma homocysteine was negatively associated with plasma folate and vitamin $B_{12}$ levels. The MMSE-KC test scores were significantly associated with plasma homocysteine and folate, but not with vitamin $B_{12}$, after adjusting for age, gender, body mass index, living with spouse, education, current smoking, energy intake, and chronic diseases such as hypertension, diabetes, thyroid disease, dyslipidemia, stroke, and cardiovascular disease. A general linear model adjusted for covariates revealed that MMSE-KC test scores increased from the lowest to the highest quartiles of vitamin $B_1$, vitamin $B_2$, vitamin $B_6$, vitamin $B_{12}$, and vitamin C intake (p for trend = 0.012, 0.039, 0.014, 0.046, 0.026, respectively). These results indicate that the problem of folate inadequacy and hyperhomocysteinemia are highly prevalent among community-dwelling elderly people and that dietary intake of the B vitamins and vitamin C is positively associated with cognitive function scores.

• Korean Journal of Veterinary Research
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• v.36 no.1
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• pp.57-63
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• 1996

The biliary excretion kinetics of the active folate derivatives were examined after an intravenous injection of methotrexate at doses of 0.3 and 10mg/kg to clarify the mechanism of the acute decrease in the plasma folate by the dihydrofolate reductase inhibitors. Even at a higher dose than used in the clinical therapy, methotrexate did not cause any acute depletion of folate denvatives in the excreted bile. Therefore, the decrease in the plasma folate appeared not to be related with the biliary excretion process of folates. A factor responsible for the plasma folate depletion by DHFR inhibitors may be due to the malabsorption of folate derivatives excreted into the small intestine.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.81-81
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• 2004

• Polymer(Korea)
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• v.29 no.2
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• pp.135-139
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• 2005

In this study, poly(ethylene imine) (PEI) modified by methoxypoly(ethylene glycol) (mPEG) and folate as a gene carrier was synthesized to decrease cytotoxicity and to improve in vivo targeting. mPEG was modified by glutaric anhydride (GA) to endow carboxylic end group, followed by the activation reaction with EDC (N-ethyl-N'-(3-dimethyl-aminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide). The activated carboxylic end group of mPEG was reacted with the amines of PEI to give mPEG graft PEI. The mPEG-folate-graft-PEI was synthesized by the reaction of mPEG-PEI with folate pre-activated by EDC/NHS. The obtained copolymers were characterized by $^1H-NMR$ and FT-IR. Gel retardation assay and fluorescence measurement indicated that DNA formed the complexes with the synthesized copolymers above N/P charge ratio 2. The size of complexes was ranging from 100 nm to 300 m. In conclusion, we confirmed that the synthesized copolymer have the possibility as a DNA carrier.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.3
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• pp.245-253
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• 2006

We evaluated the relations among exposure and urinary levels of Cr, folate, vitamin $B_{12}$ and Hcy levels in the workers chronically exposure to Cr. Subjects were 104 male employees, 65 workers exposed to Cr in 9 electroplating plants and 39 office workers who had never been occupationally exposed to hazardous substances including Cr. The geometric mean(GM) of Cr in workplace was $0.069{\pm}0.101mg/m^3$ and urinary Cr was $0.483{\pm}0.394mg/g$ creatinine and airborne Cr concentration was significantly correlated to the urinary concentration of Cr(r=0.900, p=0.000). The geometric mean concentration of urinary Cr in control group was $0.301{\pm}0.255mg/g$ creatinine. In comparing the workers exposed to Cr with controls, significantly higher mean plasma levels were found of Hcy($11.3{\pm}4.9$ vs $9.4{\pm}4.7{\mu}mol/{\ell}$, p=0.05), but vitamin $B_{12}$ levels ($181.8{\pm}68.7$ vs $216.0{\pm}64.3nmol/{\ell}$, p=0.01) was significantly decreased. Hcy concentrations correlated positively with airborne Cr concentrations(r=0.287, p=0.004) and urinary Cr concentrations(r=0.244, p=0.015) but folate concentrations correlated negatively with airborne(r=-0.234, p=0.020) and urinary Cr concentrations(r=-0.640, p=0.090), respectively. No correlations were observed between vitamin $B_{12}$, airborne and urinary Cr concentrations. Also, Hcy concentrations correlated positively with vitamin $B_{12}$(r=0.295, p=0.0020 and negatively with folate concentrations(r=-0.196, p=0.046). The various biological(i.e. age and serum indicates) or lifestyle factors(i.e. medication, smoking, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. Thus, this study found evidence that Cr might be associated with elevated plasma levels of Hcy. Furthermore, elevated plasma levels of Hcy were significantly associated with folate and vitamin $B_{12}$ concentration.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3213-3222
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• 2016

Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyl-donor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. Materials and Methods: The human cervical cancer cell line, C4-II, was grown in complete medium and medium depleted of folate (F-M+) and folate and methionine (F-M-). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT-PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. Results: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant down-regulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. Conclusions: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.