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Koichi Haraguchi

Publications and source records attributed to Koichi Haraguchi.

16 recordsLinked to original sources
PubMed2005

Concentrations of dioxins and related compounds in the blood of Fukuoka residents.

Blood samples of 152 residents (male 75 and female 77) aged 20-60 years in Fukuoka, Japan, were analyzed for dioxin toxic compounds of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) as well as 35 PCB congeners and 12 chlorinated pesticides by high-resolution gas chromatography/high-resolution mass spectrometry. Average concentrations of dioxin toxic equivalents (TEQ) from PCDDs, PCDFs, non-ortho PCBs, mono-ortho PCBs and their total in the blood of 152 residents were 10.28, 5.56, 7.75, 4.57 and 28.15 ppt in lipid, respectively. These total TEQ levels were comparable to the blood TEQ levels of normal Japanese (n=735). Lipid basis total TEQ levels progressively increased in the males from 17.1 ppt at age 20s to 47.5 ppt at age 50s and in the females from 19.5 ppt at age 20s to 54.5 ppt at age 50s. Dioxin toxic contribution of PCBs to total TEQ was increased from 31% at age 20s to 55% at age 50s. Average concentrations of total 35 PCBs and total 12 pesticides in the blood of 151 residents were 386 and 1079 ppb in lipid, respectively. Average concentrations (ppb in lipid) of total PCBs and total pesticides also progressively increased in the males from 213 and 444 at age 20s to 868 and 2140 at age 50s, respectively, and in the females from 199 and 588 at age 20s to 550 and 1977 at age 50s, respectively. The levels of TEQ, PCBs, hexachlorobenzene, beta-hexachlorocyclohexane, dieldrin, p,p'-dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyltrichloroethane, trans-nonachlor and cis-nonachlor were positively correlated with each other in most of the combinations, and the highest correlations (r>0.8) were observed between total TEQ and PCBs in both sexes.

Adult↗
PubMed2005

[Metabolism of 2, 3', 4, 4', 5-pentachlorobiphenyl in guinea pig microsomes].

The in vitro metabolism of 2,3',4,4',5-pentachlorobiphenyl (pentaCB) (CB118) was studied using liver microsomes of guinea pigs and the effect of cytochrome P450 inducers, phenobarbital (PB) and 3-methylcholanthrene (MC) on CB118 metabolism was also compared. After 30 min-incubation at 37 degrees C with liver microsomes of guinea pigs, CB118 was hydroxylated to two metabolites (M(-1) and M(-2)) with retention times of 15.84 min and 20.01 min in GC/ECD, respectively. GC/MS showed that the methylated derivative of a major metabolite M(-2) had the molecular weight of 354 and an intense fragment ion of [M(+)-50] which is a characteristic ion for PCBs possessing a methoxy-group at the 2 (2')- or the 6 (6')-position. By comparison of the mass fragmentation and the retention times in GC/MS with the synthetic authentic compounds, M(-2) was identified as 2-hydroxy-3,3',4,4',5-pentaCB (CB126). On the other hand, the methylated derivative of a minor metabolite M(-1) had the molecular weight of 320 and the similar fragment ion of [M(+)-50] to the methylated M(-2), assuming that M(-1) was a dechlorinated monohydroxy-tetrachlorobiphenyl (tetraCB) possessing hydroxy-group at the 2 (2')- or the 6 (6')-position. However, the precise structure of M-1 could not be determined because its retention time in GC was in disagreement with that of the candidate 6-hydroxy-3,3',4,4'-tetraCB. PB-treatment increased the formation of M(-1) and M(-2) to 2.2- and 6.8-fold of untreated animals, whereas MC-treatment increased only M(-2) to 2.6-fold of untreated ones. Addition of antiserum against a PB-inducible guinea pig cytochrome P450, CYP2B18, completely inhibited the formation of M(-2). These results suggest that CB118 is principally metabolized by CYP2B18 to 2-hydroxy-CB126 which is formed via a 2,3-epoxide intermediate and the subsequent NIH-shift of a chlorine at the 2-position to the 3-position in guinea pig liver.

Animals↗
PubMed2004

Comparative metabolism of polychlorinated biphenyls and tissue distribution of persistent metabolites in rats, hamsters, and Guinea pigs.

The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4- or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO(2)-CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO(2)-CBs from 2,5-dichloro-substituted PCBs, guinea pigs formed higher levels of meta-MeSO(2)-CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3',4'-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2',4'-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO(2)- and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.

Animals↗
PubMed2004

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.

We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.

Animals↗
PubMed2004

Metabolism of polychlorinated biphenyls by Gunn rats: identification and serum retention of catechol metabolites.

The tissue distributions of persistent metabolites of polychlorinated biphenyls (PCBs) in Wistar rats and homozygous uridine diphosphate glucuronosyltransferase (UGT) deficient Gunn rats exposed to 2,4,5,2',5'-pentachlorobiphenyl (CB101) and the commercial PCB mixture, Kanechlor-500 (KC500), were investigated. After exposure to CB101, four hydroxy and two methylsulfonyl (MeSO2) metabolites were detected in liver, lung, kidney, blood, and adipose tissues. One was identified as 3',4'-(OH)2-2,4,5,2',5'-pentaCB, which was retained selectively in the serum of Gunn rats. Comparative analysis of the metabolite profiles in both rat strains after exposure to KC500 showed higher formation ratios of several dihydroxy PCB metabolites in the liver of Gunn rats; major metabolites are the catechols from 2,5,3',4'-tetraCB, CB101, 2,3,6,3',4'-pentaCB, and 2,3,6,2',4',5'-pentaCB. Thus, Gunn rats effectively metabolized PCBs with 2,5- or 2,5,6-chlorine substitution to the 3,4-catechol, but less formed MeSO2 metabolites in the liver. Although both rat strains retained 4-OH-2,3,5,3',4'-pentaCB in serum, Gunn rats also retained the catechol PCBs, accounting for about 52% of the total phenolic PCBs. These results suggest that a lack of UGTs markedly alters the formation ratios and retention profiles of catechols and MeSO2 metabolites of PCBs.

Animals↗
PubMed2004

Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants routinely found in human and animal tissues. Developmental exposure to PCBs is associated with neuropsychologic deficits, which may be related to effects on thyroid hormone (TH) signaling in the developing brain. However, PCBs may interfere with TH signaling solely by reducing circulating levels of TH, or they may exert direct effects on TH receptors (TRs). Therefore, we tested whether maternal exposure to a commercial PCB mixture, Aroclor 1254 (A1254), exerts effects in the fetal brain by one or both of these mechanisms. Dams were dosed daily with 0, 1, or 4 mg/kg A1254 from gestational day 6 (GD6) until they were sacrificed on GD16. A1254 significantly reduced circulating levels of triiodothyronine (T3) and thyroxine (T4) in pregnant rats but increased the expression of several TH-responsive genes in the fetal cortex, including neuroendocrine-specific protein A (NSP-A), RC3/neurogranin, and Oct-1. These findings are consistent with a direct action of PCBs on TRs. However, we did not identify parent PCB congeners or metabolites that bound to rat TRs isolated from hepatic nuclei. These findings indicate that PCBs can interfere with TH signaling in the fetal brain by direct actions on the fetus rather than by producing maternal hypothyroidism.

Animals↗
PubMed2003

Levels and enantiomeric signatures of methyl sulfonyl PCB and DDE metabolites in livers of harbor porpoises (Phocoena phocoena) from the Southern North Sea.

The concentration of 26 methyl sulfonyl metabolites of polychlorinated biphenyls (MeSO2-PCBs) and of p,p'-DDE (MeSO2-DDE) were determined in 19 liver samples from harbor porpoises (Phocoena phocoena) stranded between 1997 and 2000 on the Belgian and French North Sea Coasts. The total concentration of MeSO2-PCBs ranged from 39 to 4221 ng/g lipid weight (lw) and were generally higher in adults (age > 2 yr, range 969-4,221 ng/g lw) than in juveniles (age < 2 yr, range 39-1815 ng/g lw). The concentrations of MeSO2-DDE were generally also higher in adults (21-96 ng/g lw) than in juveniles (0.5-60 ng/g lw). Congeners 3- and 4-MeSO2-CB101 were the dominating metabolites in all samples. Due to their preferential retention in the liver, the MeSO2-PCB congeners could be divided into two groups. The first group was dominated by the 3-MeSO2-PCB congeners and consisted of MeSO2-CB31, -CB49, -CB52, -CB87, and -CB101, which all have a 2,5-chlorine substitution in the phenyl ring containing the methyl sulfonyl group. The second group was dominated by the 4-MeSO2-PCB congeners and consisted of MeSO2-CB64, -CB91, -CB110, and -CB132, which all have a 2,3,6-chlorine substitution. The ratios of sum of PCBs/sum of MeSO2-PCBs and p,p'-DDE/MeSO2-DDE differed greatly between individual subjects and ranged from 15 to 419 and from 17 to 1088, respectively. The ratio between the precursor PCB congeners and their corresponding metabolites ranged from 0.6 (CB49) to 175 (CB174). Enantiomeric fractions (EFs) for MeSO2-PCB atropisomers, which include 3-MeSO2-CB132, 3-MeSO2-CB149, 4-MeSO2-CB149, 3-MeSO2-CB174, and 4-MeSO2-CB174, were also measured in 8 out of the 19 subjects. High enantiomeric excess (EF > 0.73 or EF < 0.23) for the measured chiral MeSO2-PCB congeners was found in all samples. This result may suggest that one atropisomer may be preferentially formed in harbor porpoises or that the atropisomers are retained in a highly selective manner.

Animals↗
PubMed2003

Renal toxicity in rats after oral administration of mercury-contaminated boiled whale livers marketed for human consumption.

Some people living in Japan have traditionally eaten the internal organs of small cetaceans (toothed whales and dolphins), and a mixed package of boiled liver, kidney, lung, and so on is still marketed for human consumption. Recently, we reported that these organs are highly contaminated with mercury. In this study, we investigated the absorption, distribution, excretion, and biochemical parameters in serum and urine after a single oral administration of boiled whale liver containing 1980 microg/g of total mercury and 23.5 microg/g of methyl mercury to rats (0.2 g boiled liver/100 g rat). The single administration of the boiled liver resulted in marked increases of the mercury concentration in the rat kidney, urinary volume, and the urinary excretion of N-acetyl-beta-D-glucosanidase, albumin, and sodium, suggesting the renal toxicity caused by inorganic mercury. Furthermore, the administration increased lactate dehydrogenase activity and creatinine, potassium, and phosphorus concentrations in serum. About 95% of total mercury dose was excreted in feces and less than 0.05% was excreted in the urine. Thus, the absorption rate of mercury from the boiled whale liver appears to be about 5% or slightly higher. These data indicate that the human consumption of boiled whale liver may cause acute intoxication by the contaminated inorganic mercury.

Administration, Oral↗
PubMed2003

Effects of polychlorinated biphenyls, kanechlor-500, on serum thyroid hormone levels in rats and mice.

Effects of a commercial polychlorinated biphenyls mixture, Kanechlor-500 (KC500), on the levels of serum thyroid hormones such as total thyroxine (T4) and triiodothyronine (T3) were examined comparatively in male Wistar rats and ddy mice. Serum T4 levels were significantly decreased in both rats and mice 4 days after a single ip injection of KC500 (100 mg/kg body weight), whereas decreased levels of T3 were observed in mice but not in rats. In addition, no significant change in the level of serum thyroid stimulating hormone was observed in either rats or mice. Hepatic UDP-glucuronosyltransferases (UDP-GTs) UGT1A1 and UGT1A6, which efficiently mediate glucuronidation of T4 and promote the excretion of the hormones, were induced by KC500 in rats but not in mice. Hepatic microsomal cytochrome P450 (P450) content and the microsomal activity for 7-ethoxy-, 7-pentoxy-, and 7-benzoyloxy-resorufin dealkylations were significantly increased by KC500 in both rats and mice, although the magnitude of increase in the enzyme activities was higher in rats than in mice. The difference in the increase in the activity of microsomal enzymes, including UDP-GT and P450, between KC500-treated rats and mice was not correlated with that in the level of hepatic methylsulfonyl-PCB metabolites. In the present study, we found for the first time that the decrease in serum T4 levels by KC-500 in mice occurred without increase in hepatic UDP-GTs, UGT1A1 and UGT1A6, responsible for T4 glucuronidation. The present findings further suggested that although the decrease in serum T4 levels in KC500-treated rats would occur at least in part through the induction of the UDP-GTs, it might not be dependent on only the increase in the enzymes.

Animals↗
PubMed2003

Distribution of methyl sulfone metabolites of polychlorinated biphenyls and p,p'-DDE in human tissues.

We determined methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) in human adipose, liver, brain, and lung tissues obtained from 11 Belgian individuals (9-62 years of age). The total concentration of MeSO2-CBs (lipid weight basis) decreased in the following order: liver (mean, 9.30 ng/g; range, 1.68-27.03 ng/g lipid) > lung [mean, 2.72 ng/g; range, not detected (ND) to 11.54 ng/g lipid] > adipose tissue (mean, 1.57 ng/g; range, 0.33-4.33 ng/g lipid) > brain (mean, 0.24 ng/g; range, ND-0.56 ng/g lipid). The profiles of MeSO2-CBs and MeSO2-DDE in each tissue were similar for all 11 subjects. In adipose, brain, and lung tissues, 4'-MeSO2-CB87, 4'-MeSO2-CB101, and 3-MeSO2-CB149 (except brain) occurred at higher concentrations than did other MeSO2-CBs. However, 3'-MeSO2-CB132 was by far the most abundant congener in liver, contributing on average to approximately 60% of the sum of MeSO2-CBs. The concentrations of 3-MeSO2-DDE in different tissues were at the same or lower levels than the total concentrations of MeSO2-CBs. This study suggests that the distribution patterns of MeSO2-CBs and MeSO2-DDE in humans differ between liver and other tissues. Moreover, these profiles differ from those found in other mammals, such as polar bears, porpoises, and otters.

Adipose Tissue↗
PubMed2003

[Peculiar remaining of some PCB congeners in the patients with Yusho for more than 30 years].

Concentrations of polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB) and dichloro dichlorophenyl ethylen (DDE) in the blood of Yusho patients (n = 28) were statistically compared with those in the blood of Fukuoka residents (n = 151). The PCB concentrations in the blood of Yusho patients were higher than those of Fukuoka controls and concentration ratios of Yusho/Control were various depending on PCB congeners, being 1.6 on 2,3',4,4',5-pentaCB (# 118), 17.5 on 2,3,3',4,4',5-hexaCB (# 156) and 5.4 on total PCBs. Correlation coefficients between age and concentrations of 7 PCB congeners, HCB and DDE in the blood of Fukuoka residents were significantly positive each other (p < 0.001), while in Yusho patients, the correlation coefficients were positive but various depending on the congeners. However, correlation coefficient between PCB # 118 and PCB # 156 in the Yusho patients was remarkably low, indicating their peculiar accumulative properties in Yusho patients. The concentration of PCB # 118 had been markedly decreased after the ingestion of PCBs and would be metabolized to hydroxylated PCB, which might cause estrogen disturbance in the Yusho patients.

Adult↗
PubMed2003

[Metabolism of 2,3,3',4,4'-pentachlorobiphenyl in hamsters].

The in vivo metabolism of 2,3,3',4,4'-pentachlorobiphenyl (CB105) was studied in hamsters and the effect of cytochrome P450 inducers, phenobarbital (PB) and 3-methylcholanthrene (MC) on its metabolism was compared to rats. After administration of CB105 intraperitoneally at a dose of 3 mg/body, four metabolites, named M-1, M-2, M-3 and M-4, were detected in 5 days-feces of all groups and the formation ratio of the metabolites M-1-M-4 was 1:39:84:0.2 in untreated hamsters and 1:19:6.7:0.7 in untreated rats. On the basis of the mass spectra of four synthetic authentic compounds and the retention times on DB-1 and MPS50 columns, M-1, M-2, M-3 and M-4 were identified as 4'-hydroxy-2,3,3',4,5'-PenCB, 5'-hydroxy-CB105, 5-hydroxy-CB105 and 4-hydroxy-2,3,3',4',5-PenCB, respectively. The pretreatment of PB and MC resulted in about 2-fold fecal excretion of four metabolites in hamsters and in about 3-fold in rats. Of four metabolites, only M-4 were detected in the serum at 5 days after CB105 administration and the concentration was 0.39 microgram/ml of hamster serum and 0.28 microgram/ml of rat serum. In hamsters, the concentration of M-4 was increased to 1.8-fold of untreated animals by PB treatment and 2.6-fold by MC treatment. On the other hand, the treatment of rats with PB and MC did not show such an increase of serum M-4. These results suggested that the hamster oxidized 2,3,4-trichloro-substituted benzene ring predominantly rather than 3',4'-dichloro-substituted benzene ring differently from the rat and that M-4 formed in hamster liver distributed to the blood and retained there to a considerable extent in comparison with that formed in rat liver.

Animals↗
PubMed2002

Mercury and selenium concentrations in the internal organs of toothed whales and dolphins marketed for human consumption in Japan.

Small cetaceans (toothed whales odontoceti and dolphins delphinidae) have been traditionally hunted along the coast of Japan and fresh red meat and blubber, as well as boiled internal organs such as liver, kidney, lung and small intestine, are still being sold for human consumption. We surveyed mercury contamination in boiled liver, kidney and lung products marketed in Japan between 1999-2001. The average +/- S.D. of total mercury (T-Hg) was 370 +/- 525 (range: 7.60 approximately 1980, n = 26) microg/g in liver, 40.5 +/- 48.5 (7.30-95.1, n = 15) microg/g in kidney and 42.8 +/- 43.8 (2.10-79.6, n = 23) microg/g in lung. A high correlation was observed between T-Hg and selenium (Se) concentrations in these organs, supporting the formation of a Hg-Se complex. The formation of a Hg-Se complex probably contribute to the detoxification of Hg for cetaceans and allows a very large accumulation of Hg in livers. The provisional permitted level of T-Hg in marine foods set by the Japanese Ministry of Health and Welfare is 0.4 microg/ g, and the provisional permitted weekly intake (PTWI) set by WHO is 5 microg/kg bw/week. The maximal T-Hg detected in boiled liver (1,980 microg/g) exceeds the permitted level by approximately 5,000 times and the consumption of only 0.15 g of liver exceeds the PTWI of 60 kg of body weight of the consumer, suggesting the possibility of an acute intoxication by T-Hg even after a single consumption of the product.

Animals↗
PubMed2002

Optimized separation and determination of methyl sulfone metabolites of polychlorinated biphenyls (PCBs) and p,p'-DDE in biota samples.

An optimised method is described for the determination of 27 methyl sulfone polychlorobiphenyls (PCBs) and DDE in biota samples. Initially, the samples were extracted by hot Soxhlet and the methyl sulfones were separated by liquid/liquid extraction with concentrated sulfuric acid and back-extracted with hexane. The parameters of the back-extraction were studied and it was found that for a quantitative extraction of the methyl sulfones from the concentrated acid layer, a 50% dilution with cold water should be done. The hexane layer containing the methyl sulfones was further cleaned-up on basic silica (33% KOH) and Florisil. After concentration, the extract was analysed by gas chromatography-mass spectrometry (GC-MS) with electron capture negative ionisation (ECNI) in selected ion monitoring mode (SIM). It was shown that, for methyl sulfones, the ion formation was dependent on the chlorine substitution, position of the MeSO2-group and the ion source temperature. If the ion source temperature was higher than 200 degrees C, [M-CH3]- was the predominant ion for most methyl sulfones. Therefore, for increased sensitivity, quantitation of most congeners was done using [M-CH3]- ions instead of the molecular ion as used in previously reported methods. The method was validated for the determination of 26 tri- to hepta- 3- and 4-substituted MeSO2-PCBs and 3-MeSO2-DDE in animal and human tissues. Good sensitivity and selectivity of the method were obtained. Limits of detection (LODs) ranged from 0.06 to 0.10 ng g(-1) lipid weight. Average recoveries of individual congeners from vegetable oil spiked with individual standards (3.33 ng g(-1)) ranged from 73 to 112% with a mean value of 89%. The coefficients of variation ranged from 5.2 to 12.2%, which is within the acceptable range for environmental analyses.

Adipose Tissue↗