• Biomolecules & Therapeutics
• /
• v.4 no.4
• /
• pp.301-309
• /
• 1996

LBD-001, a recombinant human interferon ${\gamma}$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rats (Sprague-Dawley) from day 7 to 17 of gestation at dose levels of 0.35$\times$10$^{6}$ , 0.69$\times$10$^{6}$ , and 1.38$\times$10$^{6}$ I.U./kg/day. As the control groups, hydrocortisone sodium succinate (5 or 10 mg/kg/day) was also similarly administered. Teratological effects of the test agents on fetuses and development of offsprings (F1 rats) were investigated. (1) No significant changes by the treatment of LBD-001 were observed in body weight, food and water consumption, feeding and nursing behaviors, and autopsy of pregnant or lactating mother rats. However, in hydrocortisone sodium succinate (10 mg/kg/day)-treated group, significant decreases of body weight on day 16, 18, and 20 of gestation and food consumption on day 20 of gestation and outstanding atrophy of thymus and adrenals were observed in two rats autopsied on day 20 of gestation. (2) No significant changes in resorption rate, skeletal or visceral development of fetuses, and physical or sensory development of offsprings (Fl) by the treatment of LBD-001 were detected. In hydrocortisone sodium succinate (10 mg/kg/day)-treated group, however, there were significant decreases of body weight of fetuses, delay of ossification, temporary delay of body weights of offsprings (F1) on day 1 and 3 of lactation, and increased tendency of stillborn rate and malformation rate of bone. The results show that LBD-001 at the dose of 1.38$\times$10$^{6}$ I.U./kg/day or less is not teratogenic in organogenesis of fetuses and the development of offsprings (F1). Meanwhile, hydrocortisone sodium succinate (10 mg/kg/day) seems to delay ossification of fetuses and temporarily retard the development of offsprings (Fl).

• Journal of Veterinary Clinics
• /
• v.16 no.2
• /
• pp.389-396
• /
• 1999

Pregnant rats were treated at various stages of gestation with prostaglandin analogue, cloprostenol alone or concomitant with HCG to study effects on termination of gestation and plasma estrogen and progesterone. Cloprostenol (90 or 180 mg/kg) was administered alone on 1~3, 4~6, 7~9, 9~11 or 11~13 consecutive days of gestation twice a day and in combination with HCG (50 or 100 IU/day) on days of 1~3 or 7~9 once a day. Rats were autopsied on day 21 of gestation or at 6, 12 or 24 hours after treatment on day 6 or 9, respectively. Cloprostenol was found to be nearly 100% effective in preventing implantation, destroying viable fetuses and causing preimplantation losses, but in early gestation, on days 1-3, there was little effect. And when cloprostenol administered concomitant with HCG, corpora lutea were significantly increased, implantation sites and viable fetuses significantly decreased, and pre-and post-implantation losses significantly increased in most cases. Plasma concentrations of estradiol and progesterone were significantly decreased by administering cloprostenol, and estradiol concentration significantly decreased but progesterone significantly increased by administering of cloprostenol concomitant with HCG. It is suggested that cloprostenol was more effective in terminating pregnancy than a combination of cloprostenol and HCG in the rat.

• Journal of Veterinary Clinics
• /
• v.19 no.3
• /
• pp.322-327
• /
• 2002

The effect of GnRH alone and concomitant with PMSG on the prevention of implantation. termination of pregnancy, and concentration of plasma progesterone were studied in pregnant rats. GnRH 50, 100 or 200 ug alone and concomitant with PMSG 25 or 50 IU were administered once on day 2 or 9 of gestation, respectively. Rats were autopsied on days 7 or 20. Administration of GnRH on day 2 did not result in the prevention of implantation and termination of pregnancy but resulted in termination of pregnancy administering on day 9. Administration of GnRM concomitant with PMSG on day 2 or 9 resulted in prevention of implantation and termination of pregnancy, but injection of GnRH 50 ug concomitant with PMSG 25 IU on day 9 had only one live fetus. Administration of GnRH alone and concomitant with PMSG on day 2 had no effect on the concentration of plasma progesterone determining on day 7. Administration of GnRH concomitant with PMSG on day 2 resulted in decrease of progesterone level determining on day 20 but GnRH alone was normal level. Administration of GnRH alone and concomitant with PMSG on day 9 resulted in decrease of the concentration of progesterone but was normal concentration administering GnRH 50 ug concomitant with PMSG 25 IU.

• Journal of Environmental Health Sciences
• /
• v.22 no.3
• /
• pp.17-27
• /
• 1996

The purpose of this study was to evaluate the decreasing effects of Korean garlic against the accumulation of mercury levels in maternal and fetal organs in pregnant Fischer 344 rats, based on the theory and information that neutral amino acids have protective effects against mercury poisoning and garlic contains a large of neutral amino acids. The results obtained are as follows: 1. On the 20th day of gestation, the maternal body weight in 20 mg/wt$\cdot$kg methyl mercuric chloride groups was 76.1% of those in control group, but those recovered to be 81.2% and 93.6% by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 2. The mercury levels in maternal organs were reduced 6.2% and 47.2% (p<0.05) in kidney, 8.2% and 42.1% (p<0.05) in spleen, 9.7% and 40.9% (p<0.05) in blood, 35.6% (p<0.05) and 67.2% (p<0.05) in liver, 38.0% (p<0.05) and 57.6% (p<0.05) in brain, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 3. The mercury levels were reduced 22.4% and 44.3% (p<0.05) in placenta, and 34.7% (p<0.05) and 54.9% (p<0.05) in fetal body, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 4. The mercury levels in fetal organs were reduced 17.5% and 46.7% (p<0.05) in kidney, 15.1% and 37.0% (p<0.05) in brain, 30.2% (p<0.05) and 46.7% (p<0.05) in liver, by treating with garlic (0.5 g/wt$\cdot$kg and 1.0 g/wt$\cdot$kg). 5. Mercury levels in maternal kidney were 6.73~7.71 times higher than those in fetal kidney, but those in fetal liver and brain were 1.67~2.25 times and 1.98~2.93 times higher than those in maternal liver and brain, respectively. In conclusion, Korean garlic decrease the accumulation of mercury levels in maternal and fetal organs in pregnant Fischer 344 rats as increasing the dose.

• Toxicological Research
• /
• v.26 no.3
• /
• pp.209-216
• /
• 2010

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from $6^{th}$ to $16^{th}$ of pregnancy. $IC_{50}$ values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and $28.32\;{\mu}g/ml$ and 79.34 and $23.29\;{\mu}g/ml$ in LB cell and those values of vitamin A were 8.13 and $5.94\;{\mu}g/ml$ in CNS cell and 0.81 and $0.05\;{\mu}g/ml$ in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.4
• /
• pp.409-417
• /
• 2018

Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (n=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p<0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.

• Toxicological Research
• /
• v.17 no.3
• /
• pp.225-234
• /
• 2001

The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

• Toxicological Research
• /
• v.2 no.1
• /
• pp.37-50
• /
• 1986

This paper describes the effects of nitrofen (Hi-TOK), a herbicide on the fetuses of rats. The results were observed as follows: The internal soft tissue anomalies were classified as diaphragmatic hernia, cardiac malformation (T.G.V., V.S.D., S.V.), dilatation of ventricle in brain, dilatation of renal pelvis, underdevelopment of fetal lung, shortening of cortex length and increasing of immatured glomeruli counts in the fetal kidney. The heart and diaphragm appear to be the target organs.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.05a
• /
• pp.133-133
• /
• 2002

Recently, there is an increasing nationwide concern in Korea that exposure to electric and magnetic fields (MF) in the home environment may not be safe in humans. We previously demonstrated that exposure of MF during the entire period of pregnancy did not induce any adverse effects on both pregnant dams and embryo-fetal development in rats.(omitted)

• Toxicological Research
• /
• v.24 no.1
• /
• pp.51-58
• /
• 2008

The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.