• Journal of Nutrition and Health
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• 제31권6호
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• pp.1006-1013
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• 1998

The present study was conducted to investigate the effect of different levels of ethanol ingestion on 131ate metabolism and plasma homocysteine concentration in Sprague-Dawley male rats receiving 0, 10, 30% of their caloric intake as ethanol for S weeks. Diets containing 10% ethanol had no effect on plasma and red blood cell(rbc) 131a1e. However, in rats fed a 30% ethanol diet, rbc folate increased and plasma 131ate decreased significantly, In the rats maintained first on a 30% ethanol diet for S weeks and then on a control diet for 2 weeks, the levels of plasma and rbc f31ate were normalized by withdrawal of ethanol. Urinary fo1ate excretion increased markedly in rats fed 10% and 30% ethanol diets and decreased to 51% of controls by withdrawal of ethanol. Plasma homocysteine concentration increased significantly in rats fed a 30% ethanol diet. The results suggest that chronic ingestion of ethanol increased urinary 131ate excretion markedly, which may decrease plasma 131ate and deplete liver folate.

• Journal of Nutrition and Health
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• 제33권3호
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• pp.250-256
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• 2000

Hyperhomocysteinemia has been shown to be associated with increased risks for macrovascular angiopathy. The present study was conducted to document the relationship between plasma homocysteine levels and the presence of macrovascular angiopath in patients with Type II diabetes mellitus. Plasma total homocysteine was determined by a HPLC-fluorescence detection method in a total of 238 subjects, 127 diabetic patients and 111 control. Dietary information including folate intake was assessed by a 24-hour recall in a total 113 subjects, 70 diabetic patients and 43 control. Folate intake was significantly lower inn patients with diabetes mellitus than that in the control. The lowered folate intake in the diabetic patients was mainly due to reduced intakes of fruits and vegetables. The average plasma homocysteine level of patients with MA was 14.2$\mu$㏖/L, which was significantly higher than that of either the patients without MA(11.4$\mu$㏖/L) or the control(11.5$\mu$㏖/L). Twenty five percent of the diabetic patients were positively correlated with age (r=0.20), body weight (r=0.28), body mass index (r=0.28), body mass index (r=0.18), diastolic blood pressure (r=0.20), and total cholesterol (r=0.14). cigarette smokers had significantly higher levels of plasma homocysteine than the non-smokers. Further prospective studies are needed to investigate whether folate or other B vitamin supplementation could be beneficial for the prevention of hyperhomocysteinemia or macrovascular angiopathy in the diabetic patients.

• 대한방사성의약품학회지
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• 제4권1호
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• pp.3-10
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• 2018

The folate receptor (FR) is a promising cell membrane-associated target for nuclear imaging of various cancers (via imaging $FR-{\alpha}$) and potentially also inflammatory diseases (via imaging $FR-{\beta}$), through the use of folic acid-based radioconjugates. However, there have been several drawbacks of previously reported radioconjugates, such as a short half-life of the radiolabel ($^{68}Ga\;t_{1/2}$ 68 min), a complex and time-consuming multistep radiosynthesis, and a high renal uptake of radiolabeled folate derivatives. The goal of this study was to develop an imaging probe by directly labeling folate with radioactive iodine without using an extra prosthetic group. The radiolabeling of folate was optimized using various labeling conditions and the labeled tracers were isolated by high-performance liquid chromatography. The in vitro stability of labeled folate was checked in phosphate-buffered saline and serum. The tumor-targeting efficacy of the probe was also evaluated by biodistribution studies using a murine 4T1 tumor model.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5185-5188
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• 2016

Objective: Targeted-drug-delivery based lipid nanoparticles has emerged as a new and effective approach in cancer chemotherapy. Here, we investigated the ability of folate-modified nanostructured lipid carriers (NLCs) to enhance letrozol (LTZ) efficacy in MCF-7 breast cancer cells. Methods: New formulations were evaluated regarding to particle size and scanning electron microscope (SEM) features. Anti-proliferative effects of LTZ loaded nanoparticles were examined by MTT assay. To understand molecular mechanisms of apoptosis and cell cycle progression, flow cytometric assays were applied. Results: Optimum size of nanoparticles was obtained in mean average of $98{\pm}7nm$ with a poly dispersity index (PDI) of 0.165. The IC50 value was achieved for LTZ was $2.2{\pm}0.2{\mu}M$. Folate-NLC-LTZ increased the percentage of apoptotic cells from 24.6% to 42.2% compared LTZ alone (p<0.05). Furthermore, LTZ loaded folate targeted NLCs caused marked accumulation of cells in the subG1 phase. Conclusion: Taken together, our results concluded that folate targeted LTZ can be considered as potential delivery system which may overcome limitations of clinical application of LTZ and improve drug efficacy in tumor tissue.

• Journal of Nutrition and Health
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• 제32권4호
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• pp.376-383
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• 1999

The effects of $\beta$-carotene substitutionl for vitamin A and the chronic consumption of ethanol of ethanol on hepatic folate metabolism were studied it rats. The substitution of $\beta$-carotene for vitamin A depressed hepatic 10-formyl-tetreahydrofolate dehydrogenase(10-formyl-tetrahydrofolate : NADP oxidoreductase, E.C. 1.5. 1.6)activity to 65% of controls(p<0.001) and enhanced hepatic 5, 10-methy-lenetetrahydrofolate reductase(E. C. 6.3.3.2)activity by 56% with respect to control levels(p<0.001). Hepatic activity of 10-formyltertrahydrofolate dehydrogenase was depressed to about half that of control levels by ethanol administration to rats(36% ethanol diet, p<0.001). The activity of 5, 10-methyleneterahydrofolate reductase was not changed by ethanol consumption. The increased activity of 5, 10-methyleneterahydrofolate reductase and the decreased activity of 10-formyltetrahydrofolate dehydrogenase appeared to decrease the level of nonmethyl folate conezyme and the rate of one-carbon metabolism. Plasma homocysteine concentrations were significantly higher in rats fed ethanol(p<0.01) o $\beta$-carotene(p<0.001) than in controls, which suggests that increased activity of 5, 10-methylenetetrahydrofolate reductase can depress homocysteine metabolism. We concluded that dietary substitution of $\beta$-carotene for vitamin A or chronic administration of ethanol resulted in changes in the activity of hepatic folate-dependent enzymes, which could affect the distribution of folate derivatives, plasma homocysteine levels and one-carbon metabolism.

• 한국임상약학회지
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• 제8권1호
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• pp.23-28
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• 1998

The pharmacokinetics of atenolol (25 mg/kg, i.v.) in the folate-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folate (50, 100, and 200 mg/kg). At folate dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and AUC of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The elimination rate constant $(K_{el})$ and total body clearance $(CL_t)$ of atenolol decreased significantly, and half-life ($t_{1/2}$) and mean residence time (MRT) of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The serum creatinine concentration $(S_{cr})$ correlated well (p<0.05) with half-life $(t_{1/2})$ and elimination rate constant $(K_{el})$ of atenolol, as well as BUN with AUC and total body clearance $(CL_t)$ of atenolol.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1045-1052
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• 2002

Hyperhomocysteinemia, resulted from an interaction between the mutation of MTHFR gene and B vitamin deficiency, is suggested as a possible cause for complications and adverse outcomes of pregnancy. The purpose of the present study was to investigate the relationship between the intakes of B vitamins and serum homocysteine concentrations with the C677T mutation in the MTHFR genotypes in 135 normal pregnant women of 24-28 weeks of gestation. Dietary intake of B vitamins did not differ among the three genotypes, but the negative correlation between dietary folate intake and the serum homocysteine level was the strongest in the T/T type (r ＝ -0.249) than in other genotypes (C/T: r＝ -0.040, C/C:r＝ 0.126, p＜0.05). Among the subject with the T/T type, the pregnant women who consumed folate less than 50% of the RDA had higher serum homocysteine levels than those who consumed folate greater than 125% of the RDA (10.4$\pm$5.9 vs 7.0$\pm$1.5 $\mu$mol/L, p＜0.05). Serum homocysteine levels were higher in the women with micronutrient supplements than those with no supplements in the T/T type, but such relation was not present in the C/C or the C/T type. In conclusion, serum homocysteine concentrations were influenced by the interrelationship between the MTHFR polymorphisms and dietary folate intake or micronutrient supplementation.

• 한국식품과학회지
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• 제51권5호
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• pp.425-431
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• 2019

본 연구는 국내 나물류 7종을 표준화된 5가지 다른 조리방법으로 조리 후 엽산 함량 변화 및 잔존율을 비교하였다. 엽산 함량 분석은 trienzyme-L casei 미생물법을 이용하였으며, 분석법은 정확성, 정밀성, 직선성, 검출한계 및 정량한계 등의 분석수행특성을 측정하여 검증하였으며, 내외부 분석품질관리를 수행하여 분석의 신뢰도와 숙련도를 평가하였다. 모든 분석법 검증은 AOAC에서 제시한 가이드라인에 부합하였으며, 7개월 동안 실시한 내부품질관리 및 숙련도 시험에서 모두 신뢰도 구간에 들어가는 결과를 얻어 본 실험에서 분석된 데이터의 신뢰도를 확보할 수 있었다. 조리법에 따른 나물류의 엽산 함량은 조리 전 엽산 함량과는 상관없이 조리 방법에 따라 유의적으로 다르게 나타났다. 나물의 종류에 따라 엽산 리텐션에 차이를 보였는데 비교적 튀기기 조리 후 높은 엽산 함량을 보였고, 찌기 처리된 시료에서 낮은 함량이 나타났다. 엽산 잔존율은 취나물과 쑥갓을 제외한 나물류에서는 조리에 의해 전반적으로 증가된 잔존율을 보여, 나물류는 열처리 방법을 통한 조리 후 섭취하는 것이 엽산 섭취에 보다 효율적인 것으로 나타났다. 본 연구는 조리 후 변화되는 엽산 함량에 관한 신뢰도 높은 정보를 제공하고 있으므로 이를 국가영양데이터베이스 구축에 활용 가능할 것으로 사료된다.

• Journal of Nutrition and Health
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• 제42권5호
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• pp.423-433
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• 2009

본 연구는 흰쥐를 대상으로 엽산결핍 또는 엽산결핍/비타민 $B_{12}$결핍/0.3% 호모시스틴 식이의 공급을 통해 각각 경미한 호모시스테인혈증과 중위의 호모시스테인혈증을 유도한 후, 혈장, 간 및 뇌 조직내 메티오닌 대사회로 biomarker와 엽산 농도 사이의 상관관계를 분석함으로써 영양성 호모시스테인혈증의 특성을 규명할 목적으로 실시하였다. 6 주령 Sprague-Dawley 숫컷 쥐에게 엽산이 충분한 식이 (FS), 엽산결핍식이 (FD), 또는 동일 식이에 호모시스틴을 첨가한 식이 (FSH and FDH), 엽산결핍/비타민 $B_{12}$ 결핍/호모시스틴 첨가 식이 (FDHCD)를 8주간 공급하였다. 1) FD와 FDH 식이군은 경미한 호모시스테인혈증을 (17.41 ${\pm}$ 1.94 nmol/mL) 나타냈으며, FDHCD 식이군은 중위의 호모시스테인혈증을 (44.13 ${\pm}$ 2.65 nmol/mL) 나타내어 엽산과 비타민 $B_{12}$결핍에 의한 영양성 호모시스테인혈증의 모델로 이용할 수 있었다. 2) FD, FDH, FDHCD 식이군의 간 (p < 0.001)과 뇌조직 (p < 0.01) 내 엽산 농도는 FS, FSH군 보다 유의적으로 낮았으나, FD, FDH, FDHCD 식이군의 간 및 뇌조직의 엽산농도 사이에는 유의적인 차이가 없었다. 이와 대조적으로 혈장 엽산 농도는 FDHCD 식이군 (126.5 ${\pm}$ 9.6 nmol/L)이 FD, FDH 식이군 (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001) 보다 약 6배 높았으며, 이는 비타민 $B_{12}$ 결핍에 의한"methyl-folate trap"으로 인해 엽산이 효율적으로 조직내 보유되지 못하고 혈류로 나와 소변을 통해 배설되기 때문인 것으로 보인다. 3) FD와 FDH 식이군의 간조직의 SAH 농도는 각각 대조군 보다 44% 및 50%씩 증가되었고 (p < 0.001), 간 SAM 농도는 각각 대조군 보다 72%, 71% 저하되었으며 (p < 0.001), 그 결과 두 군 모두 SAM/SAH 비율이 대조군 보다 약 80% 저하되었다 (p < 0.001). 한편 FDHCD 식 이군의 간 SAH 농도를 대조군과 비교할 때 대조군 보다 107% 증가되었고 (p < 0.001), SAM 농도는 대조군 보다 81% 저하되었으며 (p < 0.001), 그 결과 SAM/SAH 비율이 대조군 보다 약 90% 저하되어 매우 낮은 SAM/SAH 비율을 나타냈다 (p < 0.001). 뇌조직 SAM 농도는 엽산결핍, 비타민 $B_{12}$결핍 및 호모시스틴 급여에 의해 영향을 받지 않고 대조군과 유사한 수준을 보여 뇌조직내 SAM의 항상성을 나타냈으나, FDHCD 식이군의 뇌조직 SAH 농도는 대조군 보다 60% 증가되었으며 (p < 0.05), 그 결과 SAM/SAH 비율은 대조군 보다 약 28% 저하되었다 (p < 0.05). 따라서 중위의 호모시스테인혈증을 나타낸 실험군에서만 뇌조직의 SAH 농도가 증가되었다. 4) 영양결핍 (엽산 또는 비타민 $B_{12}$)에 의한 호모시스테인혈증의 특성을 조사할 목적으로 혈장, 간 및 뇌 조직내 메티오닌 대사회로 biomarker와 엽산 농도 사이의 상관관계를 조사하였다. 혈장 호모시스테인은 간 엽산과 음의 상관관계 (r = -0.641, p < 0.01)을 보였으나, 뇌 엽산 또는 혈장 엽산과는 유의적인 상관관계를 보이지 않았다. 그러나 이와 대조적으로 FDHCD 식이군을 제외시킨 나머지 네개의 실험군 자료만으로 상관관계를 분석하였을 때 혈장 호모시스테인과 뇌 엽산 (r = -0.321, p < 0.05), 혈장 엽산 (r = -0.581, p < 0.01), 간 엽산 (r = -0.684, p < 0.01) 사이에 모두 유의적인 상관관계를 나타냈다. 혈장 호모시스테인과 간조직의 SAH 및 SAM 농도 사이의 상관관계는 FDHCD군을 제외시킨 나머지 네개의 실험군 자료만으로 상관관계를 분석하였을 때 뇌조직 SAH 농도들 제외한 모든 상관계수가 전체실험군 자료로 분석한 경우보다 높았다. 따라서 엽산결핍/비타민 $B_{12}$결핍으로 인한 호모시스테인혈증 (FDHCD)에서는 혈장 엽산이 엽산결핍군 (FD, FDH)보다 높으면서 동시에 혈장 호모시스테인 농도도 높은 특성을 보였다. 결론적으로, 식이 중 엽산만 결핍된 경우와 엽산결핍과 비타민 $B_{12}$ 결핍을 동반할 경우"methyl-folate trap"으로인해 혈장 엽산과 호모시스테인 농도 패턴에 차이가 있었으며, 메티오닌 대사회로의 biomarker 사이의 상관관계와 혈장 엽산, 뇌 엽산 및 뇌 SAH와 호모시스테인 농도 사이의 상관관계가 차이가 있었다. 또한 엽산 결핍과 비타민 $B_{12}$ 결핍으로 인해 나타나는 뇌 SAH 농도의 증가는 메틸화를 저해시킴으로써 인지능력에 영향을 줄 수 있을 것으로 사료된다.

• Nutrition Research and Practice
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• 제11권5호
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• pp.419-429
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• 2017

BACKGROUND/OBJECTIVES: The relationship between folate and colorectal neoplasia remains controversial. We examined the association between serum folate concentrations and colorectal adenomas in a case-control study of Korean adults and conducted a meta-analysis. SUBJECTS/METHODS: Our case-control study included 113 pairs of case and control who underwent colonoscopy and provided blood samples. We used multivariable conditional logistic regression models to obtain the odds ratios and 95% confidence interval (CIs). For meta-analysis, we identified the relevant studies by searching the PubMed database up to February 2017, included our case-control study and combined the study-specific relative risks (RRs) using a random-effects model. RESULTS: In this case-control study, we included 58 men and 55 women with colorectal adenomas and sex and fasting status matched the controls. We did not find any significant association between the serum folate levels and colorectal adenomas in either men or women. For meta-analysis, a total of eleven studies were included in our analysis and classified into two groups; polyp clearance group (PC) for the studies that included participants who underwent endoscopies and had their polyps removed at baseline; and no polyp clearance group (NPC) for the studies that included participants whose histories of endoscopies were unknown or who underwent their first endoscopies. Four PC (1,311 cases and 1,672 non-cases) and eight NPC studies (3,501 cases and 11,347 non-cases) were included. The combined RRs (95% CIs) comparing the bottom with the top categories of circulating folate levels were 1.07 (0.97-1.18) for the NPC group but 1.45 (1.16-1.74) for the PC group. CONCLUSIONS: Low circulating folate levels were associated with new adenoma formation.