• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.220-227
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• 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.

• BMB Reports
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• v.38 no.3
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• pp.300-306
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• 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.

• 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.

• 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.

• Biomedical Science Letters
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• v.11 no.2
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• pp.175-183
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• 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.

• Journal of Food Hygiene and Safety
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• v.21 no.2
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• pp.118-128
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• 2006

This study was conducted to determination of the endocrine distruptor function of 'Parabens' by dosing ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben to the immature SD rats. 18 groups were given vehicle control group, negative control group (Dibutyl phthalate), postive control group ($1'7-{\alpha}$ Ethynylestrdiol) and each paraben groups involved 3 dose level. Rats were injected with 62.5, 250 and 1,000mg/kg from postnatal day 19 till 21 once a day in subcutaneous and a total 3, times. There was no treatment related death. but, subcutaneous nodule, edema, alopecia and scrub formation on injection site was observed. These signs was become worse in high dose level. these signs was cause from physical stimulation by test substance which parabens were mix with com oil as vehicle. In the analysis of organ weights, absolute and relative weights of brain, spleen, liver, thymus, heart, kidneys, adrenals, ovaries and vagina were no difference with control group. but, wet and blotted weight of uterus was increased in every high dose parabens treat group. Especially, all dose level of isobutyl paraben was showed increment of uterus weight. uterus dilatation of parabens treated group was observed in gross anatomic pathology and these result was agree with wet and blotted weight of uterus. In the result of this study, estrogenic effect as endocrine distruptor was observed in ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben. and it was considered isobutyl paraben has highest estrogrnic effect under the condition of this study.

• Journal of Ginseng Research
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• v.24 no.1
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• pp.8-17
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• 2000

Estrogen can influence on the expression of behaviors not associated directly with reproduction, including learning and memory. Recently estrogen has received considerable attention for its effects on neuroprotection and neural circuits in brain areas associated with cognition. Although estrogen replacement therapy may be helpful to postmenopausal women, it also results in a number of harmful side effects. Ginseng also has steroidal qualities and contains several ginsenoside components which have similar backbone structure to estrogen. The objectives of this experiment were 1) to examine the effects of estrogen and 2) to investigate the effects of ginsenosides as estrogenic agent on learning and memory using the Morris water maze, a traditional experimental task for spatial memory. In the experiments designed here, ovariectomized mice were implanted subcutaneously with Sila, itic capsules containing 17${\beta}$-estradiol (100∼250 $\mu\textrm{g}$/$m\ell$), panaxadiol (PD) and panaxatriol (PT) saponins (15∼100 $\mu\textrm{g}$/$m\ell$) diluted with sesame oil. In the first set of experiment, the effects of estradiol on learning and memory during the Morris water maze was examined. When estradiol was delivered via Silastic capsules following training improved spatial memory performance in ovariectomized female mice. In the second set of experiment, three different PD and PT saponin concentrations were delivered via Silastic implants to ovariectomized female mice and their effects were compared with estrogenic effects. Results of three separate experiments demonstrated that estradiol, PD and PT administrated by Silastic implants for 2 weeks prior to water maze training significantly improved spatial memory performance compared to ovariectomized (OVX) mice, as indicated by lower escape latency over trial. The positive effect of estradiol suggests that estrogen can affect performance on learning and memory. In addition, the positive effect of PD and PT saponins suggest that ginsenosides have an estrogen-like effects in mediating learning and memory related behavior action.

• Development and Reproduction
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• v.17 no.3
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• pp.289-297
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• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.4
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• pp.323-330
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• 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.

• Journal of Environmental Health Sciences
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• v.29 no.4
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• pp.27-34
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• 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.