• 제목/요약/키워드: estrogenic effect

검색결과 134건 처리시간 0.025초

갈근(葛根) 추출물이 cisplatin에 의해 유도된 rat mesangial cell의 apoptosis에 미치는 영향 (Effects of Puerariae Radix extract on Cisplatin-Induced Apoptosis of Rat Mesangial Cells)

  • 홍재의;신조영;주성민;전병훈;이시형
    • 동의생리병리학회지
    • /
    • 제24권2호
    • /
    • pp.220-227
    • /
    • 2010
  • Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. One of the major side effects of cisplatin is nephrotoxicity, leading to acute renal failure. Recent study has suggested a role of ROS and p53 in renal cell injury by cisplatin. We studied that protective effects of PR on cisplatin-induced apoptosis in rat mesangial cell. Rat mesangial cell was preincubated with PR (50, 100, 150 and 200 ${\mu}g/m{\ell}$) for 12 hr and then treated with 30 ${\mu}M$ cisplatin for 24 hr. Protective effect of PR on cisplatin-induced apoptosis in ECV304 cells was determined using MTT assay, FDA-PI staining, flow cytometric analysis, caspase-3 activity assay, ROS assay and western blot. Our results showed that PR inhibited in cisplatin-induced apoptosis and ROS production in ECV304 cells. Moreover, PR reduced ERK, p38 and JNK activation that increased in cisplatin-treated rat mesangial cell. Furthermore, activation of p53 by cisplatin in rat mesangial cell was inhibited by PR treatment. These results suggest that protective effect of PR on cisplatin-induced apoptosis in rat mesangial cell may be associated with reduction of ERK, p38, JNK, p53 activation.

The Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate (DDB) against Tamoxifen-induced Liver Injury in Rats: DDB Use Is Curative or Protective

  • El-Beshbishy, Hesham A.
    • BMB Reports
    • /
    • 제38권3호
    • /
    • pp.300-306
    • /
    • 2005
  • Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

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

  • 정지윤
    • 한국식품위생안전성학회지
    • /
    • 제21권4호
    • /
    • pp.258-262
    • /
    • 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.

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

  • 이봄이;이인혜;지경희
    • 한국환경보건학회지
    • /
    • 제50권3호
    • /
    • pp.201-211
    • /
    • 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.

Effect of Soy Isoflavones on the Expression of $TGF-{\beta}1$ and Its Receptors in Cultured Human Breast Cancer Cell Lines

  • Kim Young-Hwa;Jin Kyong-Suk;Lee Yong-Woo
    • 대한의생명과학회지
    • /
    • 제11권2호
    • /
    • pp.175-183
    • /
    • 2005
  • The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

  • PDF

자궁비대시험 연구에서 에틸, 프로필, 이소프로필, 부틸, 이소부틸 파라벤의 내분비독성 (Oestrogenic Activity of Parabens in Uterotrophic Assay)

  • 조은혜;정지윤;박철범;박선희;심용희;강대혁;이성호;유종훈;김선중;이성훈;박정란;이영순;강경선
    • 한국식품위생안전성학회지
    • /
    • 제21권2호
    • /
    • pp.118-128
    • /
    • 2006
  • 본 시험은 암컷 랫드에 파라벤류(에틸, 프로필, 이소프로필, 부틸, 이소부틸)를 생후 19일령부터 21일령까지3일간 투여하여 자궁비대반응을 관찰하고, 이를 토대로 시험물질의 내분비계 장애작용을 검색하고자 실시하였다. 본 시험의 투여기간 동안 사망은 발생하지 않았으나, 용량결정시험에서 관찰된 것과 같이 투여부위의 피하결절 및 부종의 증상이 관찰되었으며, 이러한 증상들은 용량의존적으로 증가되는 경향을 나타내었고, 점차 투여부위의 탈모 및 가피형성 등의 과정을 거치면 발전되었다, 이러한 증상은 투여용량이 다소 낮은 음성대조군 및 양성대조군에서 발생하지 않아, 분말상태의 시험물질이 고용량으로 현탁되어 투여되며 생긴 물리적인 영향에 의한 것으로 사료되었으며, 시험물질의 에스트로겐성의 영향과는 무관한 것으로 사료되었다. 체중, 사료 및 음수섭취량에서 대조군과 시험물질간의 영향은 없는 것으로 판단되었다. 혈중 호르몬 농도에서 혈중 에스트로겐의 농도는 음성대조군, 양성대조군 및 에틸 파라벤 투여군에서 대조군에 비해 유의성있는 감소를 보였고, 이외의 시험물질에서 차이는 관찰되지 않았다. 또한, 혈중 난포자극 호르몬 및 혈중 황체형성 호르몬의 변화도 관찰되지 않아 파라벤류에 의한 혈중 에스트로겐, 난포자극 호르몬 및 황체형성 호르몬의 변화는 없는 것으로 사료되었다. 장기중량에서 생식기계를 제외한 장기에서 시험물질에 의한 영향은 없는 것으로 사료되었으며, 또한 난소 및 질의 중량에서 시험물질과 연관된 변화는 없는 것으로 판단되었다. 그러나 자궁의 wet weight 및 blotted weigh에서는 각 시험물질군에서 대조군에 대해 증가가 관찰되었다. 이소부틸 파라벤 투여군은 모든 용량군이 자궁중량에서 유의성있는 증가를 보여 가장 에스트로겐성 영향이 큰 것으로 사료되었고, 250 및 1,000 mg/kg 투여군에서 유의성있는 증가를 보인 이소프로필 투여군이 그 다음으로 에스트로겐 영향이 큰 것으로 판단되었다. 부검결과, 자궁의 확장정도는 자궁의 중량에서 관찰된 바와 대부분 일치하였으며, 조직병리학적 검사를 통해 자궁상피세포를 관찰한 결과, 이소부틸 파라벤 투여군이 가장 높은 세포질과 핵의 비율을 나타내었으며, 이소프로필 파라벤 및 부틸 파라벤 1,000 mg/kg 투여군에서는 다소 작게 관찰되었다. 자궁의 영상분석결과, 대부분의 시험물질투여군에서 자궁직경의 장축 및 단축, 자궁벽의 최소 및 최대치에서 대조군에 대해 유의성있는 변화가 없거나 감소하는 경향을 나타냈으나, 이소부틸 파라벤 투여군의 경우에는 증가하는 경향을 나타내었다. 이상의 결과를 토대로, 에틸 파라벤, 프로필 파라벤, 이소프로필 파라벤, 부틸 파라벤, 이소부틸 파라벤에서 자궁비대 반응이 관찰되어 파란벤류의 물질은 내분비 장애물질로서 검토되어야 할 것으로 사료되며, 이소부틸 파라벤이 가장 높은 에스트로겐성 영향을 주는 것으로 판단되었다.

Estrogen Replacement Effect of Korean Ginseng Saponin on Learning and Memory of Ovariectomized Mice

  • Jung, Jae-Won;Hyewhon Rhim;Bae, Eun-He;Lee, Bong-Hee;Park, Chan-Woong
    • Journal of Ginseng Research
    • /
    • 제24권1호
    • /
    • pp.8-17
    • /
    • 2000
  • 스테로이드 호르몬의 일종인 에스트로젠은 생식기능에 영향을 미치는 것 외에 학습 및 기억과 관련된 기능에도 영향을 미치는 것으로 알려져 있다. 최근, 에스트로젠은 기억과 관련된 뇌세포 신 경망의 발달과 뇌 기능 장애를 방지할 수 있다는 부분에서 상당한 관심의 대상이되고 있다. 그러나 에스트로젠 대체 치료가 폐경기의 많은 여성들에게 도움을 주기도 하지만 여러 부작용을 유발하는 것으로도 알려져 있다 인삼 역시도 스테로이드 특성을 보이며 에스트로젠과 유사한 화학구조를 가지는 여러 성분을 가지고 있다. 본 실험의 목적은 첫째로 공간 기억력을 측정하기에 여러 장점을 가지고 있으면서 다른 어떠한 행동학적 실험보다 학습과 기억의 동물 모텔로 잘 알려진 방법인 Morris water maze를 이용하여 에스트로젠의 효과를 확인하고, 두 번째는 인삼이 학습과 기억에서 에스트로젠과 같은 효과를 나타낼 수 있는지를 확인하는 것이다. 본 실험은 인위적으로 난소를 제거한 쥐에 17$\beta$-estradiol(100~250 $\mu\textrm{g}$/ml), panaxadiol(PD), panaxatriol(PT) sapo-nins(15~100 $\mu\textrm{g}$/ml)을 sesame oil에 녹인 capsule을 implant했다. 첫 번째 실험에서 난소를 제거한 쥐에 에스트로젠을 투입했을때 학습과 기억의 효과를 확인했다. 두 번째 실험에서는 난소를 제거한 쥐에 3가지 다른 농도에서의 PD, PT를 투입했을 때 학습과 기억에 대한 에스트로젠의 효과와 비교해 보았다. 2주 동안의implant 후 water maze 실험결과 세 그룹 모두 난소를 제거한 그룹보다 기억력이 향상되었다 이러한 결과를 토대로 에스트로젠이 학습과 기억에 영향을 준다는 것을 확인할 수 있었고 PD, PT 또한 학습과 기억에 관련된 행동에서 에스트로젠과 같은 효과를 나타낼 수 있다는 것을 확인할 수 있었다. 이러한 동물모델에서의 연구를 통하여 인삼이 에스트로젠 장기결핍치료에서 나타나는 여러 호르몬 부작용을 극복할 수 있는 에스트로젠 대체물질로 개발되어 기억력 저하를 수반하는 Alzheimer's disease 및 여러 퇴행성 중추신경 질환의 치료제로 대체의학의 natural compound이용에 그 기초 기전을 제공할 수 있으리라 여긴다.

  • PDF

Expressional Changes of Water Transport-related Molecules in the Efferent Ductules and Initial Segment of Mouse Treated with Bisphenol A-Containing Drinking Water for Two Generations

  • Han, Su-Yong;Lee, Ki-Ho
    • 한국발생생물학회지:발생과생식
    • /
    • 제17권3호
    • /
    • pp.289-297
    • /
    • 2013
  • Bisphenol A (BPA) is an estrogenic endocrine disrupter. However, depending on a way of treatment, the harmful effects of BPA have not been confirmed. Also, trans-generational effects of BPA on male reproduction are still controversial. Because the reabsorption of testicular fluid in the efferent ductules (ED) and initial segment (IS) is important for sperm maturation, the present study was designed to determine trans-generational effect of BPA administrated orally on expression of water transport-related molecules in the mouse ED and IS. Ethanol-dissolved BPA was diluted in water to be 100 ng (low), $10{\mu}g$ (medium), and $1mg/m{\ell}$ water (high). BPA-containing water was provided for two generations. Expression of ion transporters and water channels in the ED and IS were measured by relative real-time PCR analysis. In the ED, BPA treatment caused expressional increases of carbonic anhydrase II, cystic fibrosis transmembrane regulator, $Na^+/K^+$ ATPase ${\alpha}1$ subunit, and aquaporin (AQP) 1. No change of $Na^+/H^+$ exchange (NHE) 3 expression was detected. BPA treatment at medium dose resulted in an increase of AQP9 expression. In the IS, the highest expressional levels of all molecules tested were observed in medium-dose BPA treatment. Generally, high-dose BPA treatment resulted in a decrease or no change of gene expression. Fluctuation of NHE3 gene expression by BPA treatment at different concentrations was detected. These findings suggest that trans-generational exposure to BPA, even at low dose, could affect gene expression of water-transport related molecules. However, such effects of BPA would be differentially occurred in the ED and IS.

조골세포 세포사멸의 Estrogen 조절에 대한 Hsp27의 영향에 관한 연구 (HSP27 CONTRIBUTES TO ESTROGEN REGULATION OF OSTEOBLAST APOPTOSIS)

  • 장현석;윤정주;임재석;권종진;최철민
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • 제30권4호
    • /
    • pp.323-330
    • /
    • 2004
  • Estrogen may promote osteoblast/osteocyte viability by limiting apoptotic cell death. We hypothesize that hsp27 is an estrogen- regulated protein that can promote osteoblast viability by increasing osteoblast resistance to apoptosis. The purpose of this study was to determine the effect of estrogen treatment and heat shock on $TNF{\alpha}$ - induced apoptosis in the MC3T3-E1 cell line. Cells were treated with 0 - 100 nM $17{\beta}$ estradiol (or ICI 182780) for 0 - 24 hours before heat shock. After recovery, apoptosis was induced by treatment with 0 - 10 ng/ml TNF${\alpha}$. Hsp levels were evaluated by Northern and Western analysis using hsp27, hsp47, hsp70c and hsp70i - specific reagents. Apoptosis was revealed by in situ labeling with Terminal Deoxyribonucleotide Transferase (TUNEL). A 5 - fold increase in hsp27 protein and mRNA was noted after 5 hours of treatment with 10 - 20 nM $17{\beta}$ estradiol prior to heat shock. Increased abundance of hsp47, hsp70c or hsp70i was not observed. TUNEL indicated that estrogen treatment also reduced (50%) MC3T3-E1 cell susceptibility to $TNF{\alpha}$ - induced apoptosis. Treatment with hsp27-specific antisense oligonucleotides prevented hsp27 protein expression and abolished the protective effects of heat shock and estrogen treatment on $TNF{\alpha}$- induced apoptosis. Hsp27 is a determinant of osteoblast apoptosis, and estrogen treatment increases hsp27 levels in cultured osteoblastic cells. Hsp27 contributes to the control of osteoblast apoptosis and may be manipulated by estrogenic or alternative pathways for the improvement of bone mass.

The Bisphenol A: A Modulator of Pregnancy in Rats

  • Kim, Pan-Gyi;Lee, Na-Rae;Hwang, Seong-Hee
    • 한국환경보건학회지
    • /
    • 제29권4호
    • /
    • pp.27-34
    • /
    • 2003
  • Bisphenol A is used in the manufacture of epoxy, polycarbonate, and corrosion-resistant unsaturated polyester-styrene resins required for food packaging materials in industrial processing. Some reports indicated the possibility of harmful effects on rats. In this study was used a method for the determination of bisphenol A in blood according to the OSHA High Performance Liquid Chromatography (HPLC) guideline. The method involved blood extraction using methylene chloride. And it was evaluated developmental and teratogenic effects in pregnant rats and second generation. The results obtained were as follows. There was a significant increase in the body weights and treated groups F1 female in liver, spleen, kidney, but according to dose-response. F1 female rat's relative body weight and absolute body weight are not different. There was a significant increase liver, spleen, kidney organ weight and reproductive organ weight epididymis, prostate gland in F1 male rats. There was a proestrous in pregnant rat, group 200 $\mu\textrm{g}$/kg, 2000 $\mu\textrm{g}$/kg, 20,000 $\mu\textrm{g}$/kg. The effect on rat treated with bisphenol A decrease organ weight and reproductive organ weight. Identification and quantitation were performed with using HPLC C18 column and using at retention time 5.5 min. The results of the detection of bisphenol A were at 20,000 $\mu\textrm{g}$/kg in average 1 $\mu\textrm{g}$/ml, 200 $\mu\textrm{g}$/kg average in 0.9 $\mu\textrm{g}$/ml blood samples. From those results, it could be concluded that the effects of pregnant rat and second generation(F1) by bisphenol A treatment during lactational period were estrogenic and bisphenol A was remained in serum at low level.