• Title/Summary/Keyword: estrogenic effects

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A 14-Day Repeated Dose Toxicity of Epimedii Herba Aqueous Extract Administered by Oral Gavage in F344 Rats

  • Han, Hyoung-Yun;Yang, Young-Su;Kim, Soo Nam;Han, Su-Cheol;Han, Kang-Hyun;Lee, Jong-Hwa;Jeong, Ja Young;Roh, Hang-Sik;Seok, Ji Hyeon;Kim, Jeong-Ah;Min, Byung-Sun
    • Natural Product Sciences
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    • v.21 no.1
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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.

Development of an Improved Menopausal Symptom-Alleviating Licorice (Glycyrrhiza uralensis) by Biotransformation Using Monascus albidulus

  • Kim, Kang Uk;Lee, Sung-Jin;Lee, Inhyung
    • Journal of Microbiology and Biotechnology
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    • v.30 no.2
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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.

Effects of 4-Nonlyphenol Exposure on $P.$ $olivaceus$ and $S.$ $schlegeli$ Vitellogenesis

  • Jung, Jee-Hyun;Bae, Sun-Hae;Baeck, Kyong-Lan;Shim, Won-Joon;Kim, Dae-Jung;Han, Chang-Hee
    • Development and Reproduction
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    • v.16 no.1
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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.

The Reproductive Toxicity by Combined Treatment of Bisphenol A and Butyl Benzyl Phthalate During Gestation, Lactation Period in Rats (Bisphenol A와 butyl benzyl phthalate 동시투여가 임신랫드와 차산자에 미치는 영향)

  • 최경호;황성희;권은아;김판기
    • Journal of Environmental Health Sciences
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    • v.30 no.2
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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.

Histopathologic Changes to Additive Effect of Endocrine Disruptors in Mice (마우스에서의 환경호르몬물질의 상가작용에 대한 조직학적인 변화)

  • Jung, Ji-Youn
    • Journal of Food Hygiene and Safety
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    • v.21 no.4
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    • pp.258-262
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    • 2006
  • To investigate additive effects of endocrine disruptors, we have histopathologically studied the exchanges of the reproductive organ to ovariectomized ICR mice. Female ICR mice were ovariectomized and then treated with endocrine disruptors after two weeks. Macroscopic exchanges, which were body weight, feed and water intake, of all groups were not seen during experiment period. Histopathological changes of uterine epithelial cells, vaginal epithelial cells, mammary glands and the diameter in uterine tubles were observed. In the results, the histopathological sensitivity to endocrine disruptors effect was more seen to the vaginal epithelial cell height than others. The additive estrogenic effects of endocrine disruptors, which were combinations of DEHP, DBP and BPA, were seen with E2 and BPA treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. It provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals.

Protective effects of saffron against zearalenone-induced alterations in reproductive hormones in female mice (Mus musculus)

  • Ahmad, Bashir;Shrivastava, Vinoy K.;Saleh, Ramadan;Henkel, Ralf;Agarwal, Ashok
    • Clinical and Experimental Reproductive Medicine
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    • v.45 no.4
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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.

Evaluation of Single and Binary Mixture Toxicity of Organic UV-Filters Using H295R Cells (H295R 세포를 활용한 유기 UV-Filters의 단일 및 혼합독성 평가)

  • Bomee Lee;Inhye Lee;Kyunghee Ji
    • Journal of Environmental Health Sciences
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    • v.50 no.3
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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.

Effects of Nonylphenol on the Population Growth of Algae, Heterotrophic Nanoflagellate and Zooplankton (내분비장애물질 Nonylphenol이 미세조류, 종속영양편모충, 동물플랑크톤의 개체군 성장에 미치는 영향)

  • Lee, Ju-Han;Lee, Hae-Ok;Kim, Baik-Ho;Katano, Toshiya;Hwang, Su-Ok;Kim, Dae-Hyun;Han, Myung-Soo
    • Korean Journal of Ecology and Environment
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    • v.40 no.3
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    • pp.379-386
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    • 2007
  • Nonylphenol (NP) has been well known as a major substance of surfactant and/or estrogenic environmental hormone. We tested toxic effects of nonylphenol on the population growth and development of aquatic organism such as algae (Microcystis aeruginosa), heterotrophic nanoflagellate (Diphylleia rotans), micro- (Brachionus calyciflorus) and macro-zooplankton (Daphnia magna) among eutrophic water food-web constituents. Dosage of NP treatment were 4 to 5 grades, according to each organism's tolerance based on pre-experiments; algae (0.01, 0.05, 0.10, 1.00 mg $L^{-1}$) Diphylleia rotans (0.5, 1,2. 5,6, 10 ${\mu}g\;L^{-1})$, Brachionus calyciflorus (0.1, 0.5, 1, 2.5, 5 ${\mu}g\;L^{-1}$), and Daphnia magna (0.5, 1, 5, 10, 50 ${\mu}g\;L^{-1}$), respectively. Toxic effects were measured by the changes of biomass of each organism after NP treatment. All experiments were triplication. As suggested, the higher concentration of NP treatment, the stronger inhibited the population growth of all organisms tested. In view of toxicity, a variety of concentration of NP showed a significant growth inhibition to organism; algae to 0.05 $mg\;L^{-1}$, D. rotans and B. calyciflorus to 1.0 ${\mu}g\;L^{-1}$, and D. magna to 5.0 ${\mu}g\;L^{-1}$, respectively. The $EC_{50}$ of each organism to the nonylphenol are as follows; 3. calyciflorus (2.49 ${\mu}g\;L^{-1}$), D. rotans (3.49 ${\mu}g\;L^{-1}$), D. magna (7.61 ${\mu}g\;L^{-1})$, and M. aeruginosa (47 ${\mu}g\;L^{-1})$. NP toxic effects on the development of zooplankton like egg production showed some differences in treatment concentration between Brachionus calyciflorus ${0.1{\sim}1NP{\mu}g\;L^{-1})$ and Daphnia magna $(0.5{\sim}5NP\;{\mu}g\;L^{-1})$. These results suggest that a strong growth inhibition of predator or grazer by the nonylphenol can stimulate the algal growth, or can play important role in evoking the nuisance algal bloom in eutrophic water with enough nutrients.

The anti-climacterium effects of red clover dry extracts combined with pomegranate concentration powder in ovariectomized rats

  • Kim, Kyung Hu;Kang, Su Jin;Choi, Beom Rak;Kim, Seung Hee;Yi, Hae Yeon;Kim, Dong Chul;Choi, Seong Hun;Han, Chang Hyun;Park, Soo Jin;Song, Chang Hyun;Ku, Sae Kwang;Lee, Young Joon
    • Journal of Society of Preventive Korean Medicine
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    • v.18 no.2
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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.

Vitellogenin as a Biomarker of Endocrine Disrupter in the Aquatic Environment

  • Ryu, Beoung-Ho
    • Journal of Food Hygiene and Safety
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    • v.14 no.4
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    • pp.408-414
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    • 1999
  • A number of chemical released into the environment eliciting their effects by disrupting normal hormonal pathways. Endocrine disrupting compounds are present in the aquatic environment and pose potential health consequences to wildlife and humans. This review are designing fur xenobiotic estrogens based on induction of the egg-yolk precursor protein vitelloge-nin. In fish of aquatic environment, it may result in decrease fertility and egg production in females or lead to reduced gonad size or feminization of genetic male fish. It has been known that male fish exposed to estrogenic compounds show induced production of vitellogenin. Vitello-genin production is normally restricted to adult females, which have elevated estrogen levels during egg production. However, vitellogenin can be induced in males by Pollution of environmental endocrine disruptors. Consequently, the presence of vitellogenin in male fish can serve as an indicator of exposure of environmental endocrine disrupting compounds. In immature fish pol-luted at low levels of environmental endocrine disrupter, vitellogenin can serve as a reliable biomarker for exposure to endocrine disrupter. This review demonstrates the utility of vitellogenin as a biomarker fur exposure to estrogenin agents in auqatic environment.

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