Biomedical subjects

T Sinjari

Publications and source records attributed to T Sinjari.

7 recordsLinked to original sources

PubMed2001

Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice.

The ability of the commercial polybrominated diphenyl ether (PBDE) preparation Bromkal 70-5 DE to alter thyroid hormone and vitamin A levels as well as microsomal enzyme activities was compared with that of the commercial polychlorinated biphenyl (PCB) preparation Aroclor 1254 in orally exposed female rats (Sprague-Dawley) and mice (C57BL/6 N). Additional mice were exposed to the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether (DE-47), or to the PCB congener 2,3,3',4,4'-pentachlorobiphenyl (CB-105). For 14 days the animals were given approximately isomolar daily oral doses of Aroclor 1254, CB-105 (both 10 mg/kg body weight), Bromkal 70-5 DE or DE-47 (both at 18 mg/kg body weight). In addition, further groups of rats and mice received a higher dose of Bromkal 70-5 DE, 36 mg/kg body weight. Bromkal 70-5 DE and DE-47 decreased plasma free and total thyroxine (T4) levels in both rats and mice, although with lower potency than that of Aroclor 1254 and CB-105. By contrast, thyroid-stimulating hormone (TSH) levels were not significantly changed in any of the groups. Reduction of hepatic vitamin A levels was seen in rats after Aroclor 1254 and Bromkal 70-5 DE exposure. A similar tendency was seen also in mice, but the effects were significant only for concentration data and not the total amount. Induction ofmicrosomal phase I enzymes, measured as ethoxy, methoxy and pentoxy resorufin O-dealkylase (EROD, MROD, PROD) activities, was greatest after exposure to Aroclor 1254/CB-105 but were also significant in the Bromkal 70-5 DE/DE-47-treated groups. However, induction of uridine diphosphoglucuronosyl transferase (UDPGT) was small and for most groups insignificant. In conclusion, the PBDE compounds studied, although having a lower potency than the PCB compounds, decreased thyroxine and vitamin A levels and induced microsomal enzyme activities. Rats were more sensitive to the observed effects than mice. Microsomal phase I activity might be related, directly or indirectly, to the T4 and vitamin A effects, whereas several factors (such as weak enzyme induction and lack of correlation with altered T4 and vitamin A levels) argue against any UDPGT-related effects.

Animals↗

PubMed1998

Hydroxylated polychlorinated biphenyls: placental transfer and effects on thyroxine in the foetal mouse.

1. At day 17 of pregnancy, 1 day after maternal intravenous administration (5-50 mumol/kg body wt) of 4-OH-3,5,3',4'-tetrachlorobiphenyl (4-OH-TCB; a CB-77 metabolite), a limited dose-dependent decrease was found both in foetal and maternal total thyroxine (T4) levels (76-81% of control at 50 mumol/kg). Similarly, a 50 mumol/kg dose of a 4-OH-3,5,2',3',4'-pentachlorobiphenyl (4-OH-PeCB1) decreased total T4 levels, whereas 4-OH-2,3,5,3',4'-pentachlorobiphenyl (4-OH-PeCB2) showed no clear effect (both 4-OH-pentaCBs are CB-105 metabolites). Earlier administration (gestation day 10 or 13) of the 4-OH-PCBs had no effect on total T4 at day 17. 2. Placental transfer of 14C-4-OH-TCB to the foetal compartment was dose-related and accumulated mainly in foetal plasma at levels 2-fold those in the maternal plasma at the dose interval 0.5-5.0 mumol/kg body wt, whereas at higher doses (20 and 50 mumol/kg body wt) the foetal and maternal plasma levels were similar. A break-point in the foetal dose/plasma concentration curve at 5.0 mumol/kg indicates saturation of a high-affinity ligand binding above this dose. 3. There was an extensive accumulation of radioactivity in the maternal liver after 14C-4-OH-TCB administration (20-30% of the administered dose). In spite of this the investigated compounds resulted in a small or no effect on EROD/MROD activity in maternal liver and these enzyme activities were not detectable in either exposed or control foetal liver.

Animals↗

PubMed1998

Hydroxylated polychlorinated biphenyls: distribution in the pregnant mouse.

1. In the pregnant C57BL mouse the disposition of a single, intravenous low dose of 14C-labelled 4-hydroxy-3,5,3',4'-tetrachlorobiphenyl (4-OH-TCB) or 4-hydroxy-3,5,2',3',4'-pentachloro-biphenyl (4-OH-PeCB1) was monitored by liquid scintillation counting and whole-body autoradiography. The compounds were placentally transferred and accumulated in the foetal tissues (e.g. plasma and liver). Also, maternal accumulation was observed in selected tissues, including liver, adrenal gland, adipose tissue and yolk sac placenta. 2. The foetal concentration of both hydroxy-PCBs increased with time up 24 h post-exposure and the foetal plasma concentration with at this time-point two-fold of that in maternal plasma. Chemical analysis of maternal plasma and liver showed no metabolism of the administered compounds. 3. In the pregnant C57BL mouse at late gestation, exposure to 4-OH-TCB generally resulted in a higher foetal and maternal tissue retention than did 4-OH-PeCB1. The estimated elimination half-lives (t 1/2) of 4-OH-TCB in maternal liver and plasma were 69 and 13 h respectively, and for 4-OH-PeCB1 were 17 and 13 h. 4. No differences in foetal tissue concentration of 4-OH-TCB were observed between the C57BL, and NMRI mouse. In contrast, earlier studies have shown that the PCB congener CB-77, the parent compound of 4-OH-TCB, resulted in a C57BL/NMRI foetal ratio of 1:5.

Animals↗

PubMed1996

Milk transfer and neonatal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice.

The selective accumulation of 3,3',4,4'-tetrachlorobiphenyl metabolites in late gestational foetal blood and soft tissues in mice as a result of administration of different coplanar polychlorinated biphenyl (PCB) congeners, is reported elsewhere. The situation in the nursing neonate after maternal exposure to the same congeners is now studied: The 14C-labelled congeners 3,3',4,4'-tetrachlorobiphenyl (IUPAC number CB-77),3,3',4,4'5-pentachlorobiphenyl (IUPAC number CB-126), 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC number CB-169) (all three non-ortho congeners) and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC number CB-105) (mono-ortho congener) were injected intravenously in lactating mice at day 11 post partum. One day and four days later, milk and neonatal/maternal tissues and plasma radioactivity was monitored by liquid scintillation counting (dose: 2.0 mumol (20-50 microCi)/kg body weight). In milk, CB-126, -169 and -105 showed higher levels (1450-2520 pmol/ml; one day after administration) than did CB-77 (580 pmol/ml), and in neonates, the relative whole-body levels of radioactivity (CB-169 and -105 highest) were related to the levels seen in milk (probably the consequences of their metabolic persistence). The comparably high 14C-concentration found in neonatal liver (about 15,000 pmol/kg) after CB-126 administration and in plasma (880 pmol/ml) after CB-77 administration could be explained by binding to specific proteins. In general, neonatal mice had two to seven times higher plasma levels than those of their mothers. These results indicate that CB-126, -169 and -105 are transferred via milk to neonates in considerable quantity and are deposited mainly in neonatal liver, whereas CB-77 is transferred in a comparably lower amount and accumulated in neonatal plasma. The lower 14C-levels in the NMRI mothers and offspring (about half of C57BL values in maternal and neonatal plasma), could possibly be explained by a differentiated metabolism of CB-77 in these two strains.

Animals↗

PubMed1996

Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice.

Earlier studies (Darnerud et al. 1986) have shown that the Ah-receptor binding polychlorinated biphenyl (PCB) congener 3,3',4,4'-tetrachlorobiphenyl (IUPAC number CB-77) accumulated as hydroxy and methylsulphone metabolites in late gestational mice foetuses. In the present paper the foetal accumulation potential in mice of other dioxin-like PCB congeners was studied: 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4',5,5'-hexachlorobiphenyl and 2,3,3',4,4'-pentachlorobiphenyl (IUPAC numbers CB-126, CB-169, CB-105, to some extent dioxin-like) were compared to results of CB-77 (all congeners 14C-labelled and in equimolar doses (2.0 mumol/kg body wt.)). CB-77 resulted in the comparatively strongest foetal 14C-accumulation, when measured in plasma or whole body homogenate four days after administration (day 17 of pregnancy); the plasma 14C-values (calculated as pmol/g wet wt.) were 760, 130, 60 and 40 for CB-77, -126, 105 and -169, respectively, and the CB-77 derived radioactivity in the foetal compartment was 3.6% of administered dose (i.e. a considerable portion of the remaining maternal body radioactivity). Thin-layer chromatography (TLC) results, suggesting extensive CB-77 metabolism and foetal metabolite uptake, support earlier findings. The effects of CB-77 and CB-169 on foetal 7-ethoxyresorufin-O-deethylase (EROD) activities (day 17 of gestation; two days after 5 mg/kg body wt. dose (14.0-17.0 mumol/kg body wt.)) was about 20 times lower than of CB-126. In the dam, high radioactivity levels were observed in the liver and fat (highest concentrations found in CB-126 and CB-105, respectively). Strain comparison-foetal 14C-uptake (four days after administration of CB-77) in C57BL mice was almost five times higher than in NMRI-may be correlated to earlier observed differences in EROD activities between these strains. The present results indicate that congener and strain differences exist regarding both foetal and maternal distribution patterns of coplanar PCB congeners and point out the difference in foetal disposition between CB-77 and the other studied congeners.

Animals↗

PubMed1996

[Left atrial contractility function in hypertension].

UNLABELLED: The purpose of this study was the assessment of the left systolic atrial function (LSAF) in 45 hypertensive subjects (HS) with left ventricular hypertrophy (LVH). (LV mass index) (LVMI) (> 134 g/m2 for men, > 110 g/m2 for women) and in 32 normal subjects (NS). The both groups were matched for age, body surface, heart rate and LV fractional shortening. Left atrial volume (LAV) was calculated by the formula: LAV = 8 A1 x A2/3 pi l in which A1 is the area of the four-chamber view, A2 is the area of the two-chamber view and L is common length in the two views. The atrial function contractility was evaluated by the following parameters: 1. LA stroke volume (LASV) = LAV - LAMV where LAV is the volume before atrial systole and LAMV is the LA minimal volume. 2. LA ejection fraction (LAEF) = LASV/LAV. 3. Atrial ejection force (AEF) = peak A/MOA in which peak A wave is the maximal late diastolic velocity and MOA is the mitral orifice area. 4. Atrial transport (AT) = A/M in which M area is under the mitral velocity curve and A-area under the late diastolic velocity curved assessed by Doppler echo. [table: see text] Thus all above parameters are significantly increased in HS. In HS, LASV is correlated to LAV (r = 0.84; p < 0.001) and to LVMI (r = 0.32; p < 0.05). LAEF is correlated to peak A (r = 0.90; p < 0.001) and LVMI (r = 0.34; p < 0.05). CONCLUSIONS: In HS with LVH in comparison with N, the increase of the LA contractility is considered to be urged by the increase of LAV (Frank-Starling's law). These data could be explained by the less distensibility of LV chamber in relation to LVH.

Adolescent↗

PubMed1993

Induction of 7-ethoxyresorufin-O-deethylase (EROD) activity in mice foetuses by the PCB-congener 3,3',4,4'-tetrachlorobiphenyl.

1. 3,3',4,4'-Tetrachlorobiphenyl (TCB) induces liver microsomal 7-ethoxyresorufin-O-deethylase (EROD) activity, and this P450 isoform, i.e. CYP 1, is involved in the metabolism of TCB. 2. TCB administered i.p. to pregnant mice (5-25 mg/kg) induced foetal as well as maternal hepatic EROD activity; in all cases the maternal induced activity was higher than the foetal activity. EROD activity of TCB-induced foetuses increased with developmental age, but decreased with the length of time after treatment. 3. Strain differences were seen; in control mice and TCB-treated dams NMRI > C57BL in EROD activity, but in transplacentally TCB-treated foetuses, C57BL > NMRI. EROD activity in non-pregnant control C57BL mice was higher than in pregnant ones, whereas no activity was seen in control foetuses. 4. Results indicate that TCB at a certain dose can induce foetal metabolism, but that earlier observed foetal accumulation at lower TCB doses is probably a consequence of transplacental transport of maternally-produced metabolites.

Animals↗