• Natural Product Sciences
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• 제21권1호
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• pp.34-41
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• 2015

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.178-186
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• 2020

Licorice (Glycyrrhiza uralensis) contains several compounds that have been reported to alleviate menopausal symptoms via interacting with estrogen receptors (ERs). The compounds exist mainly in the form of glycosides, which exhibit low bioavailability and function. To bioconvert liquiritin and isoliquiritin, the major estrogenic compounds, to the corresponding deglycosylated liquiritigenin and isoliquiritigenin, respectively, licorice was fermented with Monascus, which has been demonstrated to deglycosylate other substances. The contents of liquiritigenin and isoliquiritigenin in Monascus-fermented licorice increased by 10.46-fold (from 38.03 μM to 379.75 μM) and 12.50-fold (from 5.53 μM to 69.14 μM), respectively, compared with their contents in non-fermented licorice. Monascus-fermented licorice exhibited 82.5% of the ERβ binding activity of that observed in the positive control (17 β-estradiol), whereas the non-fermented licorice exhibited 54.1% of the binding activity in an in vivo ER binding assay. The increase in the ERβ binding activity was associated with increases in liquiritigenin and isoliquiritigenin contents. Liquiritigenin acts as a selective ligand for ERβ, which alleviates menopausal symptoms with fewer side effects, such as heart disease and hypertension, compared with a ligand for ERα. In addition, Monascus-fermented licorice contained 731 mg/kg of monacolin K, one of the metabolites produced by Monascus that reduces serum cholesterol. Therefore, Monascus-fermented licorice is a promising material for the prevention and treatment of menopausal syndrome with fewer side effects.

• 한국발생생물학회지:발생과생식
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• 제16권1호
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• pp.9-18
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• 2012

The effects of the estrogenic compound 4-nonylphenol (4-NP) on vitellogenesis in juvenile olive flounder ($Paralichthys$ $olivaceus$) and rockfish ($Sebastes$ $schlegeli$) exposed continuously at 10, 50 and $100{\mu}g{\ell}^{-1}$ levels for 7 days were compared. The expression of VTG mRNA level and protein using specific probes were examined. The levels of plasma estradiol-17 ${\beta}(E_2)$ and testosterone (T) were assessed by radioimmunoassay (RIA). Plasma $E_2$ concentrations increased significantly in two female fish species exposed to $100{\mu}g{\ell}^{-1}$ of 4-NP over concentrations in control fish. Plasma T concentrations increased in $P.$ $olivaceus$. Four days after exposure, the level of VTG mRNA expression increased in $P.$ $olivaceus$ and $S.$ $schlegeli$ exposed to $20{\mu}g{\ell}^{-1}$ of 4-NP. In addition, plasma VTG protein expression was seen in $P.$ $olivaceus$ and $S.$ $schlegeli$. In $S.$ $schlegeli$ and $P.$ $olivaceus$ exposed to 4-NP, the changes were noticed mainly in hepatocytic vaculation after 7 days of exposure. Thus, 4-NP may disrupt vitellogenesis in immature fish both directly and indirectly via disrupted steroidogenesis and liver pathology. Immature $S.$ $schlegeli$ were the most sensitive to 4-NP exposure in vitellogenesis.

• 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.

• 한국식품위생안전성학회지
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• 제21권4호
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• pp.258-262
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• 2006

환경호르몬 물질의 생체내에서의 상호작용에 의한 상자 또는 상승 작용을 알아보기 위하여 환경호르몬 물질들을 조합하여 마우스에 처치한 후 생체내에서 생식기의 변화 정도를 조직병리학적으로 관찰하였다. 암컷 ICR마우스에 난소적출술을 실시하고 2주 후에 DEHP, DBP, BPA의 환경호르몬 물질을 단독 또는 두개씩 조합하여 마우스에 피하로 주입하였다. 육안적인 변화에서는 모든 군에서 이상이 관찰 되지 않았으며, 부검 후 자궁의 무게를 측정한 결과에 있어서도 유의적인 변화를 관찰할 수 없었으나, 자궁 내 fluid존재에 있어서는 E2 단독 투여 군과 E2와 함께 투여한 모든 그룹(E2+DEHP, E2+DBP, E2+BPA)에서 관찰되었다. 조직병리학적인 관찰에 있어서는.자궁상피세포, 질 상피세포, 유선의 변화 그리고 난관 직경의 변화를 관찰하였다. 그 결과 민감도에 있어서 가장 유의적인 변화를 보인 항목은 질 상피세포의 변화였으며, 환경호르몬 물질을 두개씩 혼합하여 처치한 그룹에 있어 단독으로 처치한 그룹과 비교 시 변화의 정도가 심한 것이 일부 관찰 되었으나 통계학적으로 유의성을 가지고 있다고 결론을 내리기 는 힘들었다. 결론적으로 환경호르몬물질간의 생체내에서 상가 혹은 상승작용에 대한 명확한 결과는 도출할 수 없었으나, 환경호르몬물질이 생체내 작용하는 데에 있어서 서로 간에 상승작용을 할 수 있다는 가능성은 충분한 것으로 판단되어진다.

• Clinical and Experimental Reproductive Medicine
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• 제45권4호
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• pp.163-169
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• 2018

Objective: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. Methods: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol ($E_2$), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. Results: Serum levels of LH, FSH, $E_2$, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. Conclusion: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.

• 한국환경보건학회지
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• 제50권3호
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• pp.201-211
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• 2024

Background: Organic ultraviolet (UV) filters are widely used in sunscreen products and have been identified as an emerging contaminant. Organic UV filters co-exist with multiple components, but their mixture toxicity remains largely unknown. Objectives: We investigated the toxicity of single and binary mixtures of commonly used UV-filters using the human adrenocarcinoma (H295R) cell line. Methods: After exposure to non-cytotoxic concentrations of avobenzone (AVO), homosalate (HS), octisalate (OS), octinoxate (OMC), and octocrylene (OC), the levels of testosterone (T) and 17β-estradiol (E2) were measured. The median effective concentration (EC₅₀) values for the E2 of the individual substances were used to determine the mixture effect of four binary combinations: OMC+AVB, OMC+HS, OMC+OS, and OMC+OC. The synergistic, additive, and antagonistic effects of the mixture were determined by calculating toxic units (TU). To examine the mechanism of mixture toxicity, eight genes involved in steroidogenesis were analyzed using the real-time polymerase chain reaction. Results: The significant increase in E2 in H295R cells exposed to AVO, HS, OS, OMC, and OC suggest an estrogenic effect of the tested UV-filters. A significant decrease in T was observed in cells exposed to HS and OS. EC₅₀ values for E2 increase were 105 nM for AVO, 110 nM for HS, 120 nM for OS, 55 nM for OMC, and 80 nM for OC. Both binary mixtures consisting of OMC+HS and OMC+OS have synergistic effects. Conclusions: Our results showed that five types of UV-filter substances increase E2 in H295R cells. We examined the mixture toxicity in terms of increased estrogenicity and confirmed that E2 significantly increased when OMC was mixed with a salicylate-based UV-filters. These findings highlight the importance of determining the impact of UV filter mixtures.

• 생태와환경
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• 제40권3호
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• pp.379-386
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• 2007

계면활성제의 주된 원료이며 Estrogenic hormone으로 알려진 nonylphenol이 수중생태계 먹이망의 하등생물군 성장에 미치는 독성영향을 파악하고자, 배양중인 조류(Microcytis aeruginosa), 편모충(Diphylleia rotans), 소형 (Brachionus calyciflorus) 및 대형동물플랑크톤(Daphnia magna)에 다양한 농도로 제작된 NP을 처리하고 각 개체군의 성장 및 동물플랑크톤 B. calyciflorus, D. magna의 발생특성을 각각 조사하였다. 예비실험을 통하여, 투여농도는 개체군에 따라 조류(0.01, 0.05, 0.10, 1.00mg $L^{-1}$), Diphylleia rotans (0.5, 1, 2.5, 5, 10 ${\mu}g\;L^{-1}$), Brachionus calyciflorus (0.1, 0.5, 1, 2.5, 5 ${\mu}g\;L^{-1}$), Daphnia magna (0.5, 1, 5, 10, 50 ${\mu}g\;L^{-1}$) 등으로 $4{\sim}5$단계 농도를 처리하였으며, 독성효과는 각 개체군의 현존량 변화로 산정 하였으며 실험은 각각 3회씩 반복 실행하였다. 분석결과, 예상했던 것처럼 모든 개체군은 NP농도가 증가할수록 강한 성장 억제를 보였다. 조류실험에서는 0.05 mg $L^{-1}$, D. rotans와 B. calyciflorus는 공히 10 ${\mu}g\;L^{-1}$, 대형동물플랑크톤 D. magna는 5.0 ${\mu}g\;L^{-1}$부터 각각 유의한 성장억제를 보였다. Nonylphenol에 대한 각 개체군의 $EC_{50}$은 B. calyciflorus (2.49 ${\mu}g\;L^{-1}$) < D. rotans (3.49 ${\mu}g\;L^{-1}$) < D. magna (7.61 ${\mu}g\;L^{-1}$) < M. aeruginosa (47 ${\mu}g\;L^{-1}$) 의 순으로 나타나 NP에 대해 조류세포가 가장 강한 내성을 보인 반면 B. calyciflorus가 가장 약한 것으로 나타났다. 또한 동물플랑크톤의 발생에 있어서 B. calyciflorus는 NP농도$(0.1{\sim}1{\mu}g\;L^{-1})$, D. magna는 이보다 약간 높은 NP농도 $(0.5{\sim}5{\mu}g\;L^{-1})$에서 공히 내구란이 형성되지 않았다. 이상의 결과를 종합하여 볼 때, 조류섭식자인 편모충이나 동물플랑크톤은 모두 nonylphenol에 대하여 조류보다 내성이 극히 약하며 특히 발생계에 치명적인 영향을 받기 때문에 NP가 유입되는 수계에 있어서 섭식자 소멸로 인한 식물플랑크톤 대발생의 인자로 작용할 수 있음을 시사해 주고 있다.

• 대한예방한의학회지
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• 제18권2호
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• pp.133-145
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• 2014

Objective : In this study, the addition of dried pomegranate concentrate powder (PCP) was affected the anti-climacterium activity of red clover dry extracts (RC) in ovariectomized (OVX) rats. Materials and methods : After bilateral OVX surgery, RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg (of body weight) were orally administered, once a day for 84 days, and then the changes on the serum estradiol levels, abdominal fat pad and uterus weights were observed for estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also evaluated for hepatoprotective effects, and serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels were monitored for hypolipidemic effects. Results : As a result of OVX, the estrogen-deficient climacterium symptoms, increments of abdominal fat pad weights, serum AST, ALT, TC, LDL and TG levels with decrease of uterus and liver weights, serum estradiol levels, were demonstrated. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by continuous oral treatment of RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg, respectively. Conclusion : The results suggested that RC:PCP 2:1 mixtures synergistically increased the anti-climacterium effects of RC in OVX rats. It, therefore, is expected that RC:PCP 2:1 mixture will be promising as a new potent protective agents for relieving the climacterium symptoms.

• 한국식품위생안전성학회지
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• 제14권4호
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• pp.408-414
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• 1999

자연계에 오염되어 있는 수많은 화학 물질들은 정상적인 내분비 기능을 교란한다. 내분비 교란 물질은 수계에 오염되면 야생동물과 사람에게 건강에 미치는 영향이 크다. 본 연구는 오염물질이 생체의 내분비계를 교란시키므로서 생성되는 난황 전구체 단백질로서 환경오염의 생물체의 지표로서 비트로게닌의 생성을 유도하는 내분비 교란 물질에 대하여 고찰하였다. 수계의 환경에서 서식하고 있는 물고기는 내분비계 교란 물질에 의하여 암컷에서는 번식률과 난백의 생산이 감소되고 수컷에서는 정소의 왜소화 및 암컷화로 유도되기도 한다. 여성호르몬 작용을 하는 화학물질에 노출된 수컷은 비트로게닌의 생성을 촉진하고, 암컷에 있어서 비트로게닌의 생성은 난백을 형성하는 동안 에스트로겐의 함량을 증가시켜 정상적인 활동을 제한하기도 한다. 따라서 수컷에서의 비트로게닌은 환경에 오염된 내분비교란 물질의 오염에 의하여 생성되게 된다. 결과적으로 수컷의 물고기에서 생성된 비트로게닌은 환경에 오염된 내분비 교란물질이 어느 정도 노출되어 있는가를 결정하는 생물학적 지표로 사용할 수 있다. 특히 치어의 경우 극미량의 내분비 교란물질에 노출되어도 믿을 만한 생물지표로서 이용될 수 있다.