• 한국약용작물학회지
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• 제24권5호
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• pp.341-350
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• 2016

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5 mg/kg, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100 mg/kg) and injections of clozapine (5 mg/kg) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIA-induced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.

• 대한수의학회지
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• 제44권4호
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• pp.523-532
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• 2004

The present study was carried out to investigate the potential adverse effects of amitraz on pregnant dams after maternal exposure during the gestational days (GD) 1 through 19 in Sprague-Dawley rats. The test chemical was administered orally to pregnant rats at dose levels of 0, 3, 10, or 30 mg/kg/ day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings on GD 20 were examined. In the 30 mg/kg group, an increase in the incidence of abnormal clinical signs and death, a suppression in the body weight gain, and a decrease in the food consumption were observed. A decrease in the liver weight and increases in the kidneys, adrenal glands and heart weights were also found. Serum biochemical investigations revealed increases in the aspartate aminotransferase (AST), total bilirubin, and chloride. In addition, an increase in the fetal death and decreases in the litter size and fetal body weight were seen at caesarean section. Inthe 10 mg/kg group, an increase in the incidence of abnormal clinical signs, decreases in the food consumption and liver weight, increases in the total bilirubin and chloride, and a decrease in the fetal body weight were observed. There were no adverse effects on clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings in the 3 mg/kg group. Based on the results, it was concluded that the 19-day repeated oral dose of amitraz to pregnant rats caused increases in the clinical signs, kidneys, adrenal glands and heart weights, AST, total bilirubin and chloride and decreases in the body weight gain, food consumption and liver weight at the dose levels of above 10 mg/kg/day. Under the present experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz was considered to be 3 mg/kg/day.

• 한국환경보건학회지
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• 제31권3호
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• pp.179-186
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• 2005

The purpose of this paper was to concisely review the practical changes in MeHg concentrations in fetus and offspring throughout gestation and suckling from our recent animal and human studies. In the animal study, adult female rats were given a diet containing 5ug/g Hg (as MeHg) for 8 weeks. Then they were mated and subsequently given the same diet throughout gestation and suckling. On embryonic days 18, 20, 22 and at parturition, the concentrations of Hg in the brains of fetus were approximately 1.5-2.0 times higher than those in the mothers. However, during the suckling period Hg concentrations in the brain rapidly declined to about 1/10 of that during late pregnancy. Hg concentrations in blood also decreased rapidly after birth. In human study, Hg concentrations in red blood cells (RBC-Hg) in 16 pairs of maternal and umbilical cord blood samples were compared at birth and 3 months of age after parturition. RBC-Hg in the umbilical cords was about 1.6 times higher than those in the mothers at parturition. However, all the infants showed declines in Hg concentrations throughout the breast-feeding period. RBC-Hg at 3 months of age was about half that at birth. Both the animal and human studies indicated that MeHg exposure to the fetus might be especially high but it dramatically decreases during the suckling period. Therefore, close attention should be paid to the gestation rather than the breast-feeding period to avoid the risk of MeHg to human infants.

• BMB Reports
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• 제39권4호
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• pp.383-393
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• 2006

Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

• Toxicological Research
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• 제17권2호
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• pp.115-121
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• 2001

Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg$\cdot$ body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg$\cdot$b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg$\cdot$b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3$^{+}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) and CD3$^{-}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.

• 한국환경보건학회지
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• 제30권2호
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• pp.71-78
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• 2004

This study was performed to evaluate developmental and estrogenic activity of bisphenol A (BPA) and butyl benzyl phthalate (BBP) to the second generation of Sprague-Dawley rats ingested during gestational or lactational periods. Rats were given BPA 20$\mu\textrm{g}$/kg BBP 100mg/kg of pregnancy or lactation periods. Maternal body weight and neonatal body weight were recorded. The rats were sacrificed on day 21 after birth. Reproductive organs of dam and neonate were utilized for receptor binding assay. The plasma concentrations of BPA and MBep, one of the major metabolites of BBP were analyzed with HPLC. The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP during lactational periods showed significant organ weight changes in liver and spleen. The dams exposed during lactational periods showed significant organ weight changes not only in liver and spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However, no clear synergistic effects of BPA and BBP were noted. There was no significantly different ER$\alpha$ expression pattern between control and treated groups. However, ER$\alpha$ expression were increased in F1 male testis and female uterus. PI male showed distinct ER$\alpha$ expression, especially in the group of lactational combined exposure. Synergistic ER$\alpha$ expression was found by combined treatment of BPA and BBP. We could not find any evidences of synergistic effects on BPA and/or BBP combined administration on dams and their fetuses, except in ER$\alpha$ expression of F1 male.

• 한국환경보건학회지
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• 제37권6호
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• pp.440-449
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• 2011

Objectives: This study was designed to determine the levels of polybrominated diphenyl ethers (PBDEs) in breast milk and to evaluate the relations with factors affecting these levels. Methods: The congener levels of PBDE in 22 samples of breast milk were analyzed using a high resolution gas chromatograph with a high resolution mass detector. In accordance with our standard operating procedures, the recoveries of internal standards had to range between 68% and 118%. Since the distribution of PBDE concentrations is close to log-normal, the data were logarithmically transformed before analysis. Test subjects were healthy primipara and multipara mothers with a mean age of 32 (SD = 2.7) in 2006. Results: Seven PBDE congeners (BDE-28, 47, 99, 100, 153, 154, and 183) were detected and identified in all of the pooled breast milk samples, indicating widespread contamination from PBDEs in the environment in Korea. Residue levels of total PBDEs (sum PBDEs from tri- to hepta-BDE) ranged from 0.84-13.1 ng/g lipid with median and geometric mean levels of 2.6 ng/g lipid and 2.74 ng/g lipid, respectively. PBDE congeners 47, 99 and 153 markedly predominated and accounted for about 75% of the amount of the PBDE congeners analyzed. BDE-47 was the dominant congener in most samples, whereas BDE-153 was predominant in a few (n = 7/22). BDE-47 was highly correlated with total PBDEs (r = 0.987, p < 0.01). In analyses of the differences of the means of log transformed breast milk PBDE levels for groups of potential covariates, only breast milk BDE-47 and BDE-99 levels were significantly associated with fish (p < 0.05) and meat consumption (p < 0.01). However, we did not find significant correlations between PBDE levels and maternal age, body mass index (BMI), parity, job presence and smoking status. Conclusions: Our findings are mainly limited due to the small sampling size and low doses of PBDEs exposure. Background and human exposure data of PBDEs is lacking, and longitudinal investigations into the environment and biota are encouraged to determine the health impact on future populations in Korea.

• 생명과학회지
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• 제31권4호
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• pp.442-451
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• 2021

미세 플라스틱은 입자의 크기가 5 mm 이하인 플라스틱 조각을 말하며 미세 플라스틱의 오염은 해양 생태계와 인간의 건강과 관련되어 전 세계적인 관심사이다. 광범위하게 오염되어 있는 관계로, 미세 플라스틱은 물고기, 담치, 굴, 조개, 가리비와 같이 다양한 동물에 섭취되어 체내에 축적된다. 게다가, 섭취된 미세 플라스틱은 소장, 간, 신장 그리고 심지어 뇌에서도 높은 농도로 관찰된다. 해산물은 인간에게 있어 주요 단백질 공급원 중 하나이므로, 해산물의 소비는 인간이 미세 플라스틱에 노출되는 경로가 될 수 있다. 많은 근거들은 설치류에서 미세 플라스틱의 반복적인 경구 투여가 생식, 심장, 소화기, 내분비 그리고 심지어 신경계에서 병리적, 기능적 변화를 유도함을 가리킨다. 더욱이, 임신기와 수유기 동안 모체가 미세 플라스틱에 노출되면 새끼에서 대사의 항상성에 변화가 일어난다. 해산물은 세계적으로 3억 1천만 명 이상의 사람들에게 20% 이상의 단백질 공급원이라는 사실을 고려할 때, 미세 플라스틱은 인간의 몸에 축적되어 생리적 기능에 장애를 유발할 수 있다고 가정하는 것이 타당하다. 본 리뷰에서 우리는 해양에서 미세 플라스틱 오염의 현재 실태와 해양 동물 및 설치류에서 미세 플라스틱의 축적과 독성, 그리고 인간에게의 노출과 인간 건강에 미치는 잠재적인 영향에 대해 요약하였다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제34권1호
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• pp.37-44
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• 2023

Objectives: Tic disorders are highly heritable; however, growing evidence suggests that environmental factors play a significant role in their pathogenesis. Studies on these factors have been inconsistent, with conflicting results. Therefore, this study aimed to examine the associations of pre- and perinatal exposure to Tourette syndrome (TS) or chronic tic disorders (CTD) in Korean school-aged children. Methods: This case-control study used data from a large prospective cohort study. The primary outcome was TS/CTD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version. Demographic, pre-, and perinatal information was obtained from the maternal questionnaires. Data between the TS/CTD and control groups were compared using the chi-squared or Student's t-test, as appropriate. Two-step logistic regression analyses were used to test the association between TS/CTD and pre- and perinatal risk factors. Results: We included of 223 children (78 with TS/CTD and 145 controls). Significant differences in the demographic data between the two groups were observed. The male sex ratio, mean parental age, parental final education level, and family history of tics were included as confounders. In the final adjusted multivariable model, TS/CTD was significantly associated with antiemetic exposure during pregnancy (odds ratio [OR]=16.61, 95% confidence interval [CI] 1.49-185.22, p=0.02) and medically assisted reproduction (OR=7.89, 95% CI 2.28-27.28, p=0.01). Conclusion: Antiemetic exposure and medically assisted reproduction are significantly associated with the risk of TS/CTD. These results should be replicated in future prospective and gene-by-environment studies.

• Toxicological Research
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• 제19권3호
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• pp.181-187
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• 2003

Effects of repeated treatment with butylated hydroxyanisole (BHA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BHA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and intraperitoneally challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined. Separately, a part of rats was sacrificed for the assay of hepatic and placental GSTs activities on day 12 of gestation following 7-day treatment with BHA. Cyclophosphamide, administered on day 12 of gestation, induced 43.2% of fetal death and resorption, and 100% of malformations in live fetuses, in contrast to low fetal resorption (8.7%) and malformations (8%) in control group. The malformations include cranial defect and exencephaly (100%), micrognathia and tongue extrusion (100%), limb defects (40%), renal pelvic dilatation (39%), and cleft palate (15%). Interestingly, BHA induced GSTs activities by 62% and 46% over the control in liver and placenta, respectively, and remarkably reduced the fetal resorption (13.9%) and malformations, resulting in 62% of cranial defect and exencephaly, 68% of micrognathia and tongue extrusion, 29% of limb defects, and 14% of renal pelvic dilatation. Taken together, it is suggested that a long-term pretreatment with BHA could substantially prevent fetuses from abortion and malformations following intrauterine exposure to teratogens including cyclophosphamide by inducing phase II antioxidant enzymes such as GSTs.