Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 127 records · Page 7Linked to original sources

PubMed2000

The RNA aptamer-binding site of hepatitis C virus NS3 protease.

Nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a trypsin-like protease and is essential for processing of viral polyprotein. Accordingly, it is a potential target for anti-HCV drugs. Recently we could isolate RNA aptamers (G9-I, II, and III) which bind and inhibit NS3 protease using in vitro selection strategy. In addition, G9-I aptamer showed noncompetitive inhibition. In order to elucidate the binding site of G9-I aptamer in NS3 protease domain (deltaNS3), we carried out alanine scanning mutagenesis at positive charged residues on the surface of deltaNS3. The result of binding analysis by surface plasmon resonance measurements and protease inhibition assay clarified that Arg161 as well as Arg130 of deltaNS3 are essential for interaction with G9-I aptamer. This region appears to be a potential targeting site for anti-HCV drugs.

Amino Acid Sequence↗

PubMed2000

Synergistic effect of TNF-alpha and IL-4 on the expression of thymus- and activation-regulated chemokine in human corneal fibroblasts.

Chemokine production by resident fibroblasts contributes to the recruitment of migratory leukocytes to sites of tissue injury. The effects of cytokines on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for Th2 cells, were examined in cultured human corneal fibroblasts. The culture supernatants of cells incubated for 24 h in the absence or presence of either TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml) alone did not contain TARC detectable by ELISA. However, exposure of cells to both cytokines resulted in marked release of TARC into the culture medium in a time- and dose-dependent manner. Similarly, quantitative RT-PCR analysis revealed that the two cytokines induced a synergistic increase in the amount of TARC mRNA in the cultured fibroblasts. This synergistic effect of TNF-alpha and IL-4 on TARC production by fibroblasts may contribute to the Th2 cell infiltration and consequent tissue damage associated with allergic inflammation.

Base Sequence↗

PubMed2000

Modified guanidines as potential chiral superbases. 1. Preparation Of 1,3-disubstituted 2-iminoimidazolidines and the related guanidines through chloroamidine derivatives

Modified guanidines were explored as potential chiral superbases. Thus, chiral 1,3-dimethyl-2-iminoimidazolidines with or without 4, 5-diphenyl groups, their guanidinium salts, and the 2-iminoimidazolidines with (S)-1-phenylethyl groups on the ring nitrogens were prepared by treatment of 2-chloroimidazolinium chlorides with appropriate amines. Bicyclic guanidines were also prepared from a prolinamide using a similar procedure.

Journal Article↗

PubMed2000

Modified guanidines as potential chiral superbases. 2. Preparation Of 1,3-unsubstituted and 1-substituted 2-iminoimidazolidine derivatives and a related guanidine by the 2-chloro-1, 3-dimethylimidazolinium chloride-induced cyclization of thioureas

Simple preparation methods for modified guanidines were explored for new chiral superbases. Thus, (4S,5S)-4,5-diphenyl- and diastereomeric cyclohexane-fused 2-iminoimidazolidines were prepared from (1S,2S)-1,2-diphenylethylenediamine and (1R,2R)- or (1S,2S)-1, 2-diaminocyclohexanes through cyclization of protected thiourea intermediates with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a key reaction. In the (4S,5S)-4,5-diphenyl series 1-methyl-2-iminoimidazolidines and 2-diethylaminoimidazoline were also prepared as related guanidines.

Journal Article↗

PubMed2000

Modified guanidines as potential chiral superbases. 3. Preparation Of 1,4,6-triazabicyclooctene systems and 1,4-disubstituted 2-iminoimidazolidines by the 2-chloro-1,3-dimethylimidazolinium chloride-induced cyclization of guanidines with a hydroxyethyl substituent

Simple preparation methods of modified guanidines have been explored as potential chiral superbases. Thus, 3,7,8-trisubstituted and 3,6,7, 8-tetrasubstituted 1,4,6-triazabicyclooctene systems were prepared from (1S,2S)-1,2-diphenylethylenediamine through stepwise 2-chloro-1, 3-dimethylimidazolinium chloride (DMC)-induced cyclizations of protected thioureas to the corresponding 2-iminoimidazolidines and then of 2-(2-hydroxyethylimino)imidazolidines to the bicyclic systems. Linear guanidines with a 2-hydroxyethyl functional group were prepared by the reaction of carbodiimides with 2-amino alcohols. Reaction of linear-type guanidines with DMC followed by base treatment afforded 1,4-disubstitued 2-iminoimidazolidines. Furthermore, another type of 1,4,6-triazabicyclooctene was also prepared through double DMC-induced cyclization of guanidines with two 2-hydroxyethyl substituents.

Journal Article↗

PubMed2000

Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats.

We recently reported that leukemia inhibitory factor (LIF) enhances Ca(2+)](i) through an increase in L-type Ca(2+) current (I(Ca,L)) in adult cardiomyocytes. The aim of this study was to investigate whether LIF activates Ca(2+)-dependent signaling molecules, such as calcineurin and calmodulin kinases II and IV (CaMKII and CaMKIV), and, if so, whether these Ca(2+)-mediated signaling events contribute to LIF-mediated cardiac hypertrophy. We first confirmed that LIF increased I(Ca,L) and [Ca(2+)](i) in primary cultured rat neonatal cardiomyocytes. Calcineurin, CaMKII, and CaMKIV activities increased at 2 minutes and peaked by 1.6-, 2.2-, and 2.2-fold, respectively, at 15 minutes. Nicardipine or verapamil fully inhibited these activities. Autophosphorylation of CaMKII was also observed to parallel the timing of CaMKII activity, and this phosphorylation was blocked by nicardipine, verapamil, or EGTA. LIF treatment led to a 3-fold increase in nuclear factor of activated T cell-luciferase activity. To confirm that inositol triphosphate (IP(3))-induced Ca(2+) release from sarcoplasmic reticulum was not involved in this process, IP(3) content and phosphorylation of phospholipase Cgamma were investigated. LIF did not increase IP(3) content or phosphorylate phospholipase Cgamma. KN62 (an inhibitor of CaMKII and CaMKIV) attenuated c-fos, brain natriuretic peptide, alpha-skeletal actin, and atrial natriuretic peptide expression. KN62 suppressed the LIF-induced increase in [(3)H]phenylalanine uptake and cell size. Cyclosporin A and FK506 slightly attenuated brain natriuretic peptide but did not affect c-fos or atrial natriuretic peptide expression. Cyclosporin A significantly reduced the LIF-induced increase in [(3)H]phenylalanine uptake. These findings indicated that LIF activated CaMKII, CaMKIV, and calcineurin through an increase in I:(Ca,L) and [Ca(2+)](i) and that CaMKII, CaMKIV, and calcineurin are critically involved in LIF-induced cardiac hypertrophy.

Aniline Compounds↗

PubMed2000

Spontaneous formation of polypeptides in the interfacial thin films of amphiphilic amino acid esters: acceleration of the polycondensation and control of the structure of resultant polymers.

For the purpose of elucidating the effects of molecular arrangements on the reaction rates and the structure of products, polycondensation of long-chain esters of alpha-amino acids in the monolayer on the water surface and the LB multilayers deposited on CaF2 plates were investigated by monitoring changes of the IR spectra. Spontaneous formation of the polypeptides occurs in the mono- and multilayers at room temperature without any catalyst. The rates of polycondensation in the monolayers are markedly influenced by the degree of molecular packing. Maximum polymerizability is obtained in the vicinity of the transition region from expanded to condensed films. The rates of polycondensation in the LB films are much higher than those in the bulk solids and the molten states. The polycondensation seems to be accelerated by regular arrangements of the monomer molecules in the LB films, where the functional groups are concentrated and situated more effectively for the reaction than in the bulk states. However, the polycondensation rates in the LB films are considerably slower when compared with those in the monolayers on the water surface kept at the optimum area or surface pressure, because the molecules in the LB films deposited under high compression are packed more closely than the optimum condition. Thus, suitably close packing of the monomer molecules, retaining a particular orientation together with some conformational freedom in the monolayer, is most favorable for the polycondensation. Two probable mechanisms for the polycondensation in the Y-type multilayers have been proposed. In the assembly of head-to-head double layers of the monomer molecules, the interlayer reaction propagates by sewing up the functional groups facing each other in the adjacent layers, and the polypeptide of a helical structure or random coil can be obtained. In contrast, for the alternating assembly of the amino acid ester and non-polymerizable octadecyl acetate, the polycondensation should proceed only in each single layer (intralayer reaction) and the polypeptide of the extended beta-form can be formed. In the case of dioctadecyl glutamate LB films, as well as the monolayer on water, the resultant polypeptide is the comb-like polymer with unreacted long-alkyl ester groups as side chains and abundant in the beta-form, indicating the dominant intralayer reaction. On the other hand, in the Y-type multilayer of the equimolar mixture of dioctadecyl glutamate (with two ester groups) and octadecyl ester of lysine (with two amino groups), both of the intra- and interlayer reactions occur effectively, resulting in a two-dimensional network structure of the polypeptide. In conclusion, not only the rate of polycondensation but also the higher-order structure of the resultant polypeptides can be controlled by organized arrangements of the monomer molecules in the interfacial thin films.

Alanine↗

PubMed2000

Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir.

Using the yeast Saccharomyces cerevisiae on board the Russian space station Mir, we studied the effects of long-term space flight on mutation of the bacterial ribosomal protein L gene (rpsL) cloned in a yeast-Escherichia coli shuttle vector. The mutation frequencies of the cloned rpsL gene on the Mir and the ground (control) yeast samples were estimated by transformation of E. coli with the plasmid DNAs recovered from yeast and by assessment of the conversion of the rpsL wild-type phenotype (Sm(S)) to its mutant phenotype (Sm(R)). After a 40-day space flight, some part of space samples gave mutation frequencies two to three times higher than those of the ground samples. Nucleotide sequence analysis showed no apparent difference in point mutation rates between the space and the ground mutant samples. However, the greater part of the Mir mutant samples were found to have a total or large deletion in the rpsL sequence, suggesting that space radiation containing high-linear energy transfer (LET) might have caused deletion-type mutations.

Base Sequence↗

PubMed2000

Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial.

CONTEXT: Although the cost-effectiveness and cost-benefit of influenza vaccination are well established for persons aged 65 years or older, the benefits for healthy adults younger than 65 years are less clear. OBJECTIVE: To evaluate the effectiveness and cost-benefit of influenza vaccine in preventing influenza-like illness (ILI) and reducing societal costs of ILI among healthy working adults. DESIGN: Double-blind, randomized, placebo-controlled trial conducted during 2 influenza seasons. SETTING AND PARTICIPANTS: Healthy adults aged 18 to 64 years and employed full-time by a US manufacturing company (for 1997-1998 season, n = 1184; for 1998-1999 season, n = 1191). INTERVENTIONS: For each season, participants were randomly assigned to receive either trivalent inactivated influenza vaccine (n = 595 in 1997-1998 and n = 587 in 1998-1999) or sterile saline injection (placebo; n = 589 in 1997-1998 and n = 604 in 1998-1999). Participants in 1997-1998 were rerandomized if they participated in 1998-1999. MAIN OUTCOME MEASURES: Influenza-like illnesses and associated physician visits and work absenteeism reported in biweekly questionnaires by all participants, and serologically confirmed influenza illness among 23% of participants in each year (n = 275 in 1997-1998; n = 278 in 1998-1999); societal cost of ILI per vaccinated vs unvaccinated person. RESULTS: For 1997-1998 and 1998-1999, respectively, 95% (1130/1184) and 99% (1178/1191) of participants had complete follow-up, and 23% in each year had serologic testing. In 1997-1998, when the vaccine virus differed from the predominant circulating viruses, vaccine efficacy against serologically confirmed influenza illness was 50% (P =.33). In this season, vaccination did not reduce ILI, physician visits, or lost workdays; the net societal cost was $65.59 per person compared with no vaccination. In 1998-1999, the vaccine and predominant circulating viruses were well matched. Vaccine efficacy was 86% (P =.001), and vaccination reduced ILI, physician visits, and lost workdays by 34%, 42%, and 32%, respectively. However, vaccination resulted in a net societal cost of $11.17 per person compared with no vaccination. CONCLUSION: Influenza vaccination of healthy working adults younger than 65 years can reduce the rates of ILI, lost workdays, and physician visits during years when the vaccine and circulating viruses are similar, but vaccination may not provide overall economic benefits in most years. JAMA. 2000;284:1655-1663.

Absenteeism↗

PubMed2000

Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes.

This study was designed to investigate whether angiotensin II induces the interleukin (IL)-6 family of cytokines in cardiac fibroblasts and, if so, whether these cytokines can augment cardiac hypertrophy. Angiotensin II increased IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 mRNA by 6.5-, 10.2-, and 2.0-fold, respectively, but did not affect IL-11, ciliary neurotrophic factor, or oncostatin M in cardiac fibroblasts. Enzyme-linked immunosorbent assay revealed that angiotensin II-stimulated conditioned medium from cardiac fibroblasts contained 9.3 ng/ml IL-6 at 24 h, which was 24-fold higher than the control. It phosphorylated gp130 and STAT3 in cardiomyocytes, which was reduced with RX435 (anti-gp130 blocking antibody). It increased [(3)H]phenylalanine uptake and cell area by 44% and 86% in cardiomyocytes compared with mock medium. RX435 suppressed these increases by 26% and 38%, while TAK044 (endothelin-A/B-R blocker) suppressed them by 52% and 52%, respectively. Antisense oligonucleotides against LIF and cardiotrophin-1 blocked their up-regulation, and attenuated the conditioned medium-induced increase in [(3)H]phenylalanine uptake by 21% and 13%, respectively. The combination of antisense oligonucleotides to LIF and cardiotrophin-1 decreased their uptake by 33%. These results indicated that angiotensin II induced IL-6, LIF, and cardiotrophin-1 in cardiac fibroblasts, and that these cytokines, particularly LIF and cardiotrophin-1, activated gp130-linked signaling and contributed to angiotensin II-induced cardiomyocyte hypertrophy.

Angiotensin II↗

PubMed2000

Geranylgeranylacetone enhances expression of thioredoxin and suppresses ethanol-induced cytotoxicity in cultured hepatocytes.

Geranylgeranylacetone (GGA) has been introduced into the clinical field as an anti-ulcer drug. In addition to protective effects on gastric mucosal cells, GGA also has anti-apoptotic effects against ischemia and reperfusion injury in hepatocytes and intestinal cells. However, the molecular mechanisms of the cytoprotective or anti-apoptotic effect of GGA are largely unknown. To explore the molecular mechanism of GGA action, we focused on thioredoxin (TRX), an endogenous-redox-acting molecule. We have demonstrated that GGA induces the messenger RNA and protein of TRX and affects the activation of transcription factors, AP-1 and NF-kappaB, and that GGA blunted ethanol-induced cytotoxicity of cultured hepatocytes. These results provide evidence suggesting that a possible novel molecular mechanism of GGA is to protect cells via the induction of TRX and the activation of transcription factors such as NF-kappaB and AP-1.

Animals↗

PubMed2000

Cruise ships: high-risk passengers and the global spread of new influenza viruses.

In 1997, passengers on North American cruises developed acute respiratory illnesses (ARIs); influenza was suspected. We reviewed 1 ship's medical records for 3 cruises: cruise 1 (31 August to 10 September 1997), cruise 2 (11-20 September 1997), and cruise 3 (20-30 September 1997). Medically attended ARI was defined as any 2 of the following symptoms: fever (temperature, > or =37.8 degrees C) or feverishness, sore throat, cough, nasal congestion, chills, myalgia, and arthralgia. During cruise 2, we collected nasopharyngeal swabs for viral culture from people with ARI and surveyed passengers for self-reported ARI (defined as above except feverishness was substituted for fever). The outbreak probably began among Australian passengers on cruise 1 (relative risk, 3.3; 95% confidence interval, 1.89-5.77). Of 1284 passengers on cruise 2, 215 (17%) reported ARI, 994 (77%) were aged > or =65 years, and 336 (26%) had other risk factors for respiratory complications. An influenza strain not previously identified in North America was isolated. We concluded that an "off-season" influenza outbreak occurred among international travelers and crew on board this cruise ship.

Adolescent↗

PubMed2000

Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.

The present study is part of a program to obtain effective chemopreventive agents with low toxicity from medicinal herbs and traditional herbal medicines. We previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix) inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the present investigation, we found Sanshishi (Gardeniae fructus) and the traditional herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively. Adverse effects, evidenced by body weight loss, were weaker with OGT than component herbs. To investigate their mechanisms of action, the influence on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied. Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably contributing to their suppressive effects on ACF development. The results suggest that OGT may be useful for colon cancer chemoprevention in terms of efficacy and toxicity.

Animals↗

PubMed2000

Inhibition by parthenolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1.

Excessive nitric oxide production by inducible nitric oxide synthase (iNOS) in stimulated inflammatory cells is thought to be a causative factor of cellular injury in inflammatory disease states. Compounds inhibiting iNOS transcriptional activity in inflammatory cells are potentially anti-inflammatory. An assay method for estimating iNOS transcriptional activity in the human monocyte cell line THP-1 was established using a luciferase reporter gene system. In this study, we demonstrate that parthenolide, the predominant sesquiterpene lactone in European feverfew (Tanacetum parthenium), exerts potent inhibitory effects on the promoter activity of the iNOS gene in THP-1 cells. Parthenolide effectively suppressed iNOS promoter activity in a dose-dependent manner at concentrations higher than 2. 5 microM, with an IC(50) of about 10 microM. A tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), significantly increased the iNOS promoter-dependent reporter gene activity, and the TPA-induced increase in iNOS promoter activity was effectively suppressed by parthenolide, with an IC(50) of approximately 2 microM. The present findings may further explain the anti-inflammatory property of parthenolide.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells.

Well-established mechanisms for regulation of protein activity include thiol-mediated oxidoreduction in addition to protein-protein interactions and phosphorylation. Nucleoredoxin (NRX), glutaredoxin (GRX), and thioredoxin (TRX) have been shown to act as a potent thiol reductase and reactive oxygen species regulator. They constitute a oxidoreductase superfamily and have been suggested as a candidate operating in the redox regulation of gene expression. We demonstrated here that intracellular localization of these redox molecules differ from each other and that the redox molecules differentially regulate NF-kappaB, AP-1, and CREB activation induced by TNFalpha, PMA, and forskolin and by expression of signaling intermediate kinases, NIK, MEKK, and PKA in HEK293 cells. This is a first report that describes involvement of NRX and GRX and differences from TRX in transcriptional regulation of NF-kappaB, AP-1, and CREB in living cells.

3T3 Cells↗

PubMed2000

Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach.

A gene encoding embryonic chicken pepsinogen (ECPg), a zymogen of the digestive enzyme pepsin, is expressed specifically in epithelial cells of glands of embryonic stage proventriculus (glandular stomach) under the influence of mesenchyme. We found four GATA and one Sox binding motifs in 1.1 kb of the 5' flanking region of the ECPg gene which are essential to the organ-specific expression of the gene. The expression of cGATA-5 and cSox2 in the proventriculus from day 6 to day 12 of incubation was therefore analyzed. cGATA-5 was more strongly expressed in glandular epithelial cells than in luminal epithelial cells, while cSox2 gene expression was weaker in glandular epithelial cells. Using heterologous recombination explants we also discovered that the expression of cGATA-5 and cSox2 in epithelial cells was affected by mesenchyme when the latter induced ECPg gene expression in epithelial cells. Introduction of expression constructs into epithelial cells by electroporation demonstrated that cGATA-5 upregulated transcription of a reporter luciferase gene via a cis element in the 5' flanking region of the ECPg gene. The gel mobility shift assay revealed that the cGATA-5 protein specifically binds to the GATA binding sites. cSox2 downregulated the activity of luciferase but it was not through the Sox binding motif. These results suggest that cGATA-5 positively regulates transcription of the ECPg gene and is involved in spatial regulation of the pepsinogen gene during development.

Animals↗

PubMed2000

Inhibition selectivity of grapefruit juice components on human cytochromes P450.

Five compounds including furanocoumarin monomers (bergamottin, 6', 7'-dihydroxybergamottin (DHB)), furanocoumarin dimers (4-¿¿6-hydroxy-71-¿(1-hydroxy-1-methyl)ethyl-4-methyl-6-(7-oxo-7H- furo¿3,2-g1benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimethyl- 2-octenyl]oxy]-7H-furo[3,2-g]¿1benzopyran-7-one (GF-I-1) and 4-¿¿6-hydroxy-7¿¿4-methyl-1-(1-methylethenyl)-6-(7-oxo-7H-furo¿3, 2-g1benzopyran-4-yl)-4-hexenylŏxy-3, 7-dimethyl-2-octenylŏxy-7H-furo¿3,2-g1benzopyran-7-one (GF-I-4)), and a sesquiterpene nootkatone have been isolated from grapefruit juice and screened for their inhibitory effects toward human cytochrome P450 (P450) forms using selective substrate probes. Addition of ethyl acetate extract of grapefruit juice into an incubation mixture resulted in decreased activities of CYP3A4, CYP1A2, CYP2C9, and CYP2D6. All four furanocoumarins clearly inhibited CYP3A4-catalyzed nifedipine oxidation in concentration- and time-dependent manners, suggesting that these compounds are mechanism-based inhibitors of CYP3A4. Of the furanocoumarins investigated, furanocoumarin dimers, GF-I-1 and GF-I-4, were the most potent inhibitors of CYP3A4. Inhibitor concentration required for half-maximal rate of inactivation (K(I)) values for bergamottin, DHB, GF-I-1, and GF-I-4 were calculated, respectively, as 40.00, 5. 56, 0.31, and 0.13 microM, whereas similar values were observed on their inactivation rate constant at infinite concentration of inhibitor (k(inact), 0.05-0.08 min(-1)). Apparent selectivity toward CYP3A4 does occur with the furanocoumarin dimers. In contrast, bergamottin showed rather stronger inhibitory effect on CYP1A2, CYP2C9, CYP2C19, and CYP2D6 than on CYP3A4. DHB inhibited CYP3A4 and CYP1A2 activities at nearly equivalent potencies. Among P450 forms investigated, CYP2E1 was the least sensitive to the inhibitory effect of furanocoumarin components. A sesquiterpene nootkatone has no significant effect on P450 activities investigated except for CYP2A6 and CYP2C19 (K(i) = 0.8 and 0.5 microM, respectively).

Aryl Hydrocarbon Hydroxylases↗

PubMed2000

Amounts and variation in grapefruit juice of the main components causing grapefruit-drug interaction.

A method for the determination of three furocoumarins containing two new chemicals (GF-I-1 and GF-I-4) in commercially available grapefruit juice and grapefruit itself was developed using high-performance liquid chromatography (HPLC). These components isolated from grapefruit juice have 5-geranyloxyfurocoumarin dimer structures showing extremely high affinities for a form of cytochrome P450 (CYP3A4). Considerable differences were observed on the contents among commercial brands and also batches. The contents were determined to be 321.4+/-95.2 ng/ml GF-I-1, 5641.2+/-1538.1 ng/ml GF-I-2 and 296.3+/-84.9 ng/ml GF-I-4 in twenty-eight white grapefruit juices. These chemicals were not detected in beverages from orange, apple, grape and tangerine, except that trace amount of GF-I-2 and GF-I-4 were found in lemon juice. The average levels of these furocoumarins were lower in the juice from red grapefruit than a white one. The highest level of these components were found in the fruit meat.

Beverages↗