Veterinary drug, 17ß-trenbolone promotes the proliferation of human prostate cancer cell line through the Akt/AR signaling pathway.

Trenbolone acetate (TBA) is a synthetic anabolic steroidal growth factor that is used for rapid muscle development in cattle. The absorbed TBA is hydrolyzed to the active form, 17ß-trenbolone (17 TB; 17ß-hydroxy-estra-4,9,11-trien-3-one) in meat and milk products, which can cause adverse health effects in humans. Similar to 5α-dihydrotestosterone (DHT), 17 TB was reported to exhibit endocrine disrupting effects on animals and humans due to its androgenic effect via binding to the androgen receptor. The purpose of this study is to investigate the molecular mechanism of cell proliferation in prostate cancer (PCa) cells treated with 17 TB. We found that 17 TB induces AR-dependent cell proliferation in the human prostate cancer cell line, 22Rv1 in a concentration dependent manner. Treatment with 17 TB increased the expression of cell cycle regulatory proteins, cyclin D2/CDK-4 and cyclin E/CDK-2, whereas the expression of p27 was down-regulated. Furthermore, phosphorylation of Rb and activation of E2F were also induced, which suggests the activation of cyclin D2/CDK-4 and cyclin E/CDK-2 in the cells. When 22Rv1 cells were exposed to 30 pM of 17 TB, which is the effective concentration (EC50) value required to observe proliferative effects on 22Rv1 cells, the expression levels of the phosphorylated forms of Akt and GSK3ß were increased. This study demonstrates that 17 TB induces AR-dependent proliferation through the modulation of cell cycle-related proteins in the Akt signaling pathway. The present study provides an effective methodology for identifying cell proliferation signaling of veterinary drugs that exert AR agonistic effects.

Assessment of androgen receptor agonistic/antagonistic effects on 25 chemicals in household applicants by OECD in vitro stably transfected transcriptional activation assays.

The aim of this study is to assess the androgen receptor (AR) agonistic/antagonistic effects on various chemicals, which are used in household products including cleaning agents and wetted tissues by in vitro OECD test guideline No. 458 (using AR-EcoScreen™ cell line) and the me-too test method (using 22Rv1cell line), which was adopted as OECD project No. 4.99. All chemicals were not determined as AR agonists. However α-dodecyl-ω-hydroxypoly (oxyethylene) and 3-iodo-2-propynyl butylcarbamate have shown a weak AR antagonistic effects with IC50 values of 2.18 ±â€¯0.12 and 4.26 ±â€¯0.17 µg/ml via binding affinity to AR in only 22Rv1/mouse mammary tumor virus using AR transcriptional activation assay, because of their different cytotoxicity on each applied cell line. This report firstly provides information about agonistic/antagonistic effects against human AR of various chemicals including surfactants and biocides by OECD in vitro stably transfected transcriptional activation assays. However, further in vivo and human model studies are needed to confirm their adverse effects.

In vitro OECD test methods applied to screen the estrogenic effect of chemicals, used in Korea.

In this study, 27 chemicals found in household products, which became an issue in Korea were screened for the agonistoc and antagonistic effects against human estrogen receptor using official Organization for Economic Cooperation and Development (OECD) in vitro assays, STTA assay using ERα-HeLa-9903 cell line and BG1Luc ER TA assay. In the case of human ER agonist screening by two assays, all tested chemicals did not show agonist effect against ER. In ER antagonist test by BG1Luc ER TA assay, five surfactants α-dodecyl-ω-hydroxypoly(oxyethylene), alcohols C16-18 ethoxylated, nonylphenol, ethoxylated, 3,6,9,12,15,18,21-heptaoxatritriacontan-1-ol, and α-dodecyl-ω-hydroxypoly(oxy-1,2-ethanediyl)) were found to exhibit weak antagonistic activities. The agonist/antagonist effects against human estrogen receptor of various chemicals, used in Korea by OECD test guideline are reported in this study. These results indicated that two OECD in vitro assays will can be applied in Korea by screening of agonistic/antagonistic effects against human ER of various chemicals.

Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Risk assessment based on urinary bisphenol A levels in the general Korean population.

Bisphenol A (BPA) is a high-volume industrial chemical used in the global production of polycarbonate plastics and epoxy resins, which are used in food and drink containers, such as tableware (plates and mugs). Due to its broad applications, BPA has been detected in human blood, urine and breast milk as well as environmental substances, including water, indoor and outdoor air, and dust. Indeed, exposure to high concentrations of BPA can result in a variety of harmful effects, including reproductive toxicity, through a mechanism of endocrine disruption. Our comparison of reported BPA urinary concentrations among different countries revealed that exposures in Korea may be higher than those in other Asian countries and North America, but lower than or similar to those in European countries. The current study included a total of 2044 eligible subjects of all ages. The subjects were evenly divided between males and females (48.58% and 51.42%, respectively). The geometric mean (GM) of pre-adjusted (adjusted) urinary BPA concentrations was 1.83µg/L (2.01µg/g creatinine) for subjects of all ages, and there was no statistically difference in BPA concentrations between males (1.90µg/L, 1.87µg/g creatinine) and females (1.76µg/L, 2.16µg/g creatinine). Multiple regression analysis revealed only one positive association between creatinine pre-adjusted urinary BPA concentration and age (ß=-0.0868, p<0.001). The 95th percentile levels of 24-hour recall (HR), food frequency questionnaires (FFQ) and estimated daily intake (EDI) through urinary BPA concentrations were 0.14, 0.13, and 0.22µg/kg bw/day, respectively. According to the Ministry of Food and Drug Safety (MFDS), a tolerable daily intake (tDI) of 20µg/kg bw/day was established for BPA from the available toxicological data. Recently, the European Food Safety Authority (EFSA) established a temporary TDI of 4µg/kg bw/day based on current toxicological data. By comparing these TDIs with subjects' exposure, we conclude that there are no health concerns for any age group as a result of current levels of dietary exposure to BPA.

Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study.

Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67-6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301µg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009-2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of study may be used to establish a nationally representative baseline of exposure to parabens in risk assessment.

Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity.

Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen receptor (ER)-α and ER-beta (ER-ß) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER-dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK.

Polyphenols prevent lipid abnormalities and arterial dysfunction in hamsters on a high-fat diet: a comparative study of red grape and white persimmon wines.

SCOPE: We compared the effects of two dealcoholized wines, persimmon (P) and Merlot (M), in hypercholesterolemic hamsters. METHODS AND RESULTS: Four groups of hamsters received a standard (ST) or an atherogenic diet (AT) for 12 weeks. AT animals received either dealcoholized persimmon wine (AT + P) or Merlot wine (AT + M) by gavage, while controls received water (AT and ST). Plasma cholesterol, triglycerides and glucose and paraoxonase activity were measured. Oxidative stress was assessed by aortic O(2)°(-) production, and vascular function was evaluated in aortic rings. The atherogenic diet led to higher plasma triglycerides (246%), total cholesterol (142%), LDL-cholesterol (91%) and HDL-cholesterol (49%). Aortic production of O(2)°(-) also increased (207%) and vascular reactivity was modified with altered endothelial function as assessed by acetylcholine-dependent vasorelaxation. The two wines partially prevented these alterations, reducing O(2)°(-) production and improving vascular reactivity without altering endothelial function. There was no difference between the P and M groups, although the procyanidin composition of the two dealcoholized fractions differed significantly, and only dimer concentrations were similar. CONCLUSION: These findings indicate that polyphenols are responsible, at least in part, for the antiatherogenic/antioxidant effects of wines.

Raspberry juice consumption, oxidative stress and reduction of atherosclerosis risk factors in hypercholesterolemic golden Syrian hamsters.

The effects of raspberries on early atherosclerosis in Syrian hamsters were investigated using three juices prepared from var. Cardinal, Glen Ample and Tulameen berries. The hamsters received an atherogenic diet for 12 weeks and at the same time a juice at a daily dose corresponding to the consumption of 275 ml by a 70 kg human. A control group received the same diet with water instead juice. The principal polyphenolic compounds in the juices were anthocyanins and ellagitannins, which were present at concentrations of 218-305 µg mL(-1) and 45-72 µg mL(-1), respectively. The three juices had similar but not identical effects. They all inhibited cardiac and aortic production of superoxide anion and increased hepatic glutathione peroxidase activity although only Tulameen juice brought about a significant increase in superoxide dismutase activity. Glen Ample was the only juice to significantly increase plasma paraoxonase activity. All the juices lowered plasma triglyceride level while consumption of Tulameen and Cardinal, but not Glen Ample, significantly lowered plasma total cholesterol and LDL-cholesterol. Cardinal was the sole juice to significantly increase HDL-cholesterol and likewise it also significantly reduced body weight. These findings suggest that moderate consumption of raspberry juices can help to prevent the development of early atherosclerosis, with the underlying mechanisms related to improved antioxidant status and serum lipid profiles.