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Sample records for phytoestrogen puerarin-mediated cytoprotection

  1. Dietary intake of phytoestrogens

    NARCIS (Netherlands)

    Bakker MI; SIR

    2004-01-01

    The dietary intake of phytoestrogens supposedly influences a variety of diseases, both in terms of beneficial and adverse effects. This report describes current knowledge on dietary intakes of phytoestrogens in Western countries, and briefly summarizes the evidence for health effects. The

  2. Phytoestrogens in Human Pregnancy

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    John Jarrell

    2012-01-01

    Full Text Available Background. The hormonal milieu associated with pregnancy has become a focus of interest owing to potential links with the developmental origins of health and disease. Phytoestrogens are hormonally active plant-derived chemicals that may have an impact on human reproductive processes. However, developmental exposure to phytoestrogens has not been well characterized and thus our objective was to quantify phytoestrogen exposure during pregnancy and lactation. Methods. Women in the second trimester of pregnancy entered the study during counseling for prenatal genetic information. Women who had an indication for a genetic amniocentesis on the basis of late maternal age were approached for inclusion. They completed an environmental questionnaire; a sample of amniotic fluid was collected for karyotype, blood was collected from women during pregnancy and at birth, from the umbilical cord and breast milk. Samples were tested for the presence of daidzein and genistein by GC Mass Spectroscopy. Findings. Phytoestrogens are commonly found in pregnant women’s serum and amniotic fluid during pregnancy. There is a sex difference in the concentrations with higher levels in amniotic fluid containing female fetuses. This difference was not present in maternal serum. Soy ingestion increases amniotic fluid phytoestrogen concentrations in female and male fetuses. The presence and concentrations of phytoestrogens did not differ in relation to common pregnancy complications or preexisting infertility.

  3. Phytoestrogens: a viable option?

    Science.gov (United States)

    Russell, Lori; Hicks, G Swink; Low, Annette K; Shepherd, Jinna M; Brown, C Andrew

    2002-10-01

    Estrogen replacement therapy is one of the most commonly prescribed medicines in the United States by traditional medical professionals. Over the past decade, the market for complementary/ alternative therapies for hormone replacement has dramatically increased. Women are seeking more "natural" alternatives to treat menopausal symptoms. Well-designed randomized clinical trials are often lacking, as is the information on efficacy and safety. This article will review several popular herbal therapies for menopausal symptoms including phytoestrogens, black cohosh (Cimicifuga racemosa), dong quai (Angelica sinensis), chast tree (Vitex agnus-castus), and wild Mexican yam. Their use, mechanism of action, and adverse effects are outlined.

  4. The potential health effects of dietary phytoestrogens

    NARCIS (Netherlands)

    Rietjens, Ivonne M.C.M.; Louisse, Jochem; Beekmann, Karsten

    2017-01-01

    Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)oestrogenic effects by binding to the oestrogen receptors. The aim of the present review is to

  5. Phytoestrogens and soy products: perspectives of application

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    Sergei V. Jargin

    2013-04-01

    Full Text Available Isoflavones and their metabolites are termed phytoestrogens because they bind to estrogen receptors, although weakly compared to physiologic estrogens. Soybean is the main source of phytoestrogens. Several recent reviews concluded that there is no evidence that phytoestrogens relieve menopausal symptoms better than placebo. At the same time, some studies suggest their efficacy. In theory, the use of phytoestrogens for hormone replacement appears irrational: biological action of estrogens is receptor-mediated; the question is therefore, why the vegetable analogues should be used instead of physiological hormones optimally complementary to the receptors. Apparently, the problem should be seen within the scope of placebo marketing under the guise of evidence-based medications. For example, a supposed anti-atherogenic effect of phytoestrogens was confirmed by doubtful experiments with cell cultures, which are discussed here. Furthermore, there is a contradiction: phytoestrogens are supposed to compensate for estrogen deficiency in menopause; but at the same time, their estrogenic potential does not prevent the widespread use of soy for infant food and other foodstuffs. Environmentally relevant doses of phytoestrogens have impacts on ovarian differentiation, fertility and genderrelated behavior in animals. In conclusion, the beneficial and potentially harmful effects of phytoestrogens should be clarified by independent research, which can be of importance for the future of the soybean in agriculture. [J Intercult Ethnopharmacol 2013; 2(2.000: 67-72

  6. EFFECTS OF PHYTOESTROGENS ON MAMMALIAN REPRODUCTIVE PHYSIOLOGY

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    Socorro Retana-Márquez

    2011-11-01

    Full Text Available Global consumption of phytoestrogens and their effects have increased both in animals and humans due to the augmented use of legumes in animal diets as well as the increase in vegetarian diets in some human populations. Even though the general opinion and that of clinicians toward phytoestrogens is generally positive, many phytoestrogens are now recognized as endocrine disruptor compounds, capable of interfering with the synthesis, secretion, transport, binding, action or elimination of natural hormones in the body that are responsible for reproduction. The effects of phytoestrogens mainly depend on the type, amount and plant species ingested. These compounds are found widely in a variety of plants and fodder, and can have adverse effects mainly on the reproductive tract in most animal species. Many phytoestrogens can act as estrogenic agonists or antagonists, and their effects can vary from infertility to an estrogenic over-response, thus increasing secretions in the reproductive tract and disrupting animal behavior. Presently, there is still a lack of knowledge on this subject, and the effects on reproductive parameters of estrogenic forage in animal production systems are unknown. Therefore, it is necessary to continue research in order to elucidate the effects of phytoestrogens, the doses at which effects are seen, the species, the disruptive or beneficial effects, as well as the mechanisms of action involved. This review focuses on the effects of phytoestrogens in the reproductive physiology of livestock and human, as well as the knowledge obtained from research in animal models.

  7. Soy and phytoestrogens: possible side effects

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    Jargin, Sergei V.

    2014-12-01

    Full Text Available [english] Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

  8. Dietary Phytoestrogens and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Kurzer, Mindy S; Slaton, Joel

    2007-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  9. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.

    Science.gov (United States)

    Landete, J M; Arqués, J; Medina, M; Gaya, P; de Las Rivas, B; Muñoz, R

    2016-08-17

    Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

  10. Behavioral changes in fish exposed to phytoestrogens

    International Nuclear Information System (INIS)

    Clotfelter, Ethan D.; Rodriguez, Alison C.

    2006-01-01

    We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, β-sitosterol, and the positive control 17β-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17β-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes. - Environmentally relevant concentrations of phytoestrogens reduce aggressive behavior in fish

  11. Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

    Science.gov (United States)

    Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

    2018-01-01

    Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. [Research progress in phytoestrogens of traditional Chinese medicine].

    Science.gov (United States)

    Zhao, Yuan; Zheng, Hong-Xia; Xu, Ying; Lin, Na

    2017-09-01

    Phytoestrogens are plant-derived compounds, which have a similarity in structure with human endogenous estrogen 17-β-estradiol. Structural likeness enables phytoestrogens to interact with estrogen receptors, not simply mimicking the effects of human steroidal estrogen but also exhibiting similar and divergent actions. The global literature relating to phytoestrogen in recent years was systematically summarized in this paper. Chemical compositions of phytoestrogens were mainly flavonoids, coumarins, lignans, terpenoids, steroids, etc., with a character of prevention and treatment of perimenopausal syndrome, osteoporosis, cardiovascular disease, metabolic diseases, cancer, regulation of brain function and other pharmacological effects. The mechanisms of action mainly included classical estrogen receptor pathway, epigenetic effect, activation of 5'-adenosyl-phospho-activated protein kinase, inhibition of kinase, activation of peroxisome proliferator-activated receptor, regulation of apoptosis-related proteins, inhibition of nuclear factor κB signaling pathway and so on. According to their efficacy classification, phytoestrogens were mainly distributed in the tonifying medicines, blood-activating and stasis-resolving medicines and heat-clearing medicines. The classical prescriptions with estrogen activity included tonifying formula, Qi-regulating formula and harmonizing formula, etc. This review was aimed at providing a certain reference for the further study of phytoestrogens by researchers and clinicians. Copyright© by the Chinese Pharmaceutical Association.

  13. [Phytoestrogens in the treatment of menopause].

    Science.gov (United States)

    Remport, Júlia; Blázovics, Anna

    2017-08-01

    In previous centuries many women did not even live until their menopause years due to poor economic conditions, deficiencies of medicine, epidemics and wars. Nowadays in the developed countries, people live until they are 75-80 years old, and with the expansion of average age, the number of people affected by menopause and the years spent in that state increase. Nowadays women spend one third of their lives in the menopausal stage. The only effective way to treat unpleasant symptoms for centuries was with the use of herbs, and the knowledge about them spread through oral tradition. In the 20th century, this therapeutic form was pushed into the background by the development of synthetic drug production and the introduction of hormone replacement therapy. Thanks to the influence of media in the 20th century, women began to have the social need for preserving their beauty and youth for as long as they could. Hormone replacement therapy enjoyed great popularity because women were temporarily relieved of their life quality-impairing menopausal symptoms, but years later it turned out that hormone replacement therapy could pose serious risks. A distinct advantage of herbal therapy is the more advantageous side-effect-profile opposite the used synthetics in hormone replacement therapy. Women are therefore happy to turn to valuable and well-tried natural therapies, which have been used for thousands of years. There is growing interest in herbal remedies. Studying the effects of phytoestrogens has now become an active area for research. However, the results of studies in animals and humans are controversial, some sources suggest that phytoestrogens are effective and safe, other authors claim that they are ineffective in menopause or they have particularly dangerous properties, and cannot be recommended to everyone. It is important to address this issue for the sake of health, mental health and safety of women, and so it is necessary to assess the benefits and the risks

  14. Does an apple a day keep the doctor away because a phytoestrogen a day keeps the virus at bay? A review of the anti-viral properties of phytoestrogens.

    Science.gov (United States)

    Martin, J H J; Crotty, S; Warren, P; Nelson, P N

    2007-02-01

    From dengue to herpes and influenza to AIDS, the phytoestrogens that are present in many fruits and vegetables have been shown to exert anti-viral properties. Here we review the various different anti-viral mechanisms employed by phytoestrogens.

  15. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Science.gov (United States)

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

    2010-01-01

    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  16. Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women

    NARCIS (Netherlands)

    Schouw, van der Y.T.; Pijpe, A.; Lebrun, C.E.I.; Bots, M.L.; Peeters, P.H.M.; Staveren, van W.A.; Lamberts, S.W.J.; Grobbee, D.E.

    2002-01-01

    Objective¿ Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake. Methods and Results¿ Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979

  17. Incomplete metabolism of phytoestrogens by gut microbiota from children under the age of three.

    Science.gov (United States)

    Gaya, Pilar; Sánchez-Jiménez, Abel; Peirotén, Ángela; Medina, Margarita; Landete, José Maria

    2018-05-01

    Phytoestrogens are plant-derived polyphenols with structural and functional similarities to mammalian oestrogens. The aim of this work was to study the metabolism of phytoestrogens by children's intestinal microbiota and to compare it with previous results in adults. Faecal samples of 24 healthy children were subjected to phytoestrogen fermentation assay. Only one child produced equol, while O-desmethylangolensin was found in all. Urolithin production was detected in 14 children and enterolactone in 10. Further comparison with the metabolism of phytoestrogens by adult intestinal microbiota reflected that glycitein, dihydrogenistein, urolithins D and E, enterolactone, secoisolariciresinol and arctigenin were the most important metabolites differentiating between adult and child microbial gut metabolism. Although the child intestinal microbiota showed the ability to metabolise isoflavones, ellagitannins and lignans to a certain extent, it generally showed a reduced metabolism of phytoestrogens, with a lack of 5-hydroxy equol and enterodiol, and less urolithins and enterolactone producers.

  18. Determination of Phytoestrogen Content in Fresh-Cut Legume Forage

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    Pavlína Hloucalová

    2016-07-01

    Full Text Available The aim of the study was to determine phytoestrogen content in fresh-cut legume forage. This issue has been much discussed in recent years in connection with the health and safety of feedstuffs and thus livestock health. The experiments were carried out on two experimental plots at Troubsko and Vatín, Czech Republic during June and July in 2015. Samples were collected of the four forage legume species perennial red clover (variety “Amos”, alfalfa (variety “Holyně”, and annuals Persian clover and Alexandrian clover. Forage was sampled twice at regular three to four day intervals leading up to harvest and a third time on the day of harvest. Fresh and wilted material was analyzed using liquid chromatography–mass spectrometry (LC-MS. Higher levels ( p < 0.05 of isoflavones biochanin A (3.697 mg·g −1 of dry weight and formononetin (4.315 mg·g −1 of dry weight were found in red clover than in other species. The highest isoflavone content was detected in red clover, reaching 1.001% of dry matter ( p < 0.05, representing a risk for occurrence of reproduction problems and inhibited secretion of animal estrogen. The phytoestrogen content was particularly increased in wilted forage. Significant isoflavone reduction was observed over three to four day intervals leading up to harvest.

  19. Therapeutic Perspectives of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops

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    Kateřina Štulíková

    2018-03-01

    Full Text Available Hop (Humulus lupulus L., as a key ingredient for beer brewing, is also a source of many biologically active molecules. A notable compound, 8-prenylnaringenin (8-PN, structurally belonging to the group of prenylated flavonoids, was shown to be a potent phytoestrogen, and thus, became the topic of active research. Here, we overview the pharmacological properties of 8-PN and its therapeutic opportunities. Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and post-menopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women. Application of 8-PN in the treatment of menopause has been clinically examined with promising results. Other activities that have already been assessed include the potential to prevent bone-resorption or inhibition of tumor growth. On the other hand, the use of phytoestrogens is frequently questioned regarding possible adverse effects associated with long-term consumption. In conclusion, we emphasize the implications of using 8-PN in future treatments of menopausal and post-menopausal symptoms, including the need for precise evidence and further investigations to define the safety risks related to its therapeutic use.

  20. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

    DEFF Research Database (Denmark)

    Boberg, Julie; Mandrup, Karen; Jacobsen, Pernille Rosenskjold

    2013-01-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold “high human dietary intake” mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol...... genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels...

  1. Estrogenic effects of phytoestrogens in brown trout (Salmo trutta)

    DEFF Research Database (Denmark)

    Nielsen, Louise Marie; Holbech, Henrik; Bjerregaard, Poul

    2010-01-01

    , the potential effect of the waterborne phytoestrogens on endemic fish species is largely unknown. In the present investigation, the estrogenic effect of biochanin A was tested in brown trout through water exposure experiments. Juvenile brown trout of both sexes were exposed to different concentrations...... of biochanin A. In a ten day exposure experiments, NOEC and LOEC for plasma vitellogenin induction in brown trout were found to be 0.8µg biochanin A/L and 1.2µg biochanin A/L, respectively. A six hour pulse experiment resulted in NOEC and LOEC for induction of plasma vitellogenin in brown trout of 48µg...... biochanin A/L and 186µg biochanin A/L, respectively. Investigations of the ability of genistein to induce vitellogenin synthesis in brown trout are ongoing....

  2. Phytoestrogens dietary intake and health status of retiree from middle-notrh Slovakia region

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    Jozef Čurlej

    2015-12-01

    Full Text Available Phytoestrogens found in foods of plant origin presents chemical substances that possess a wide range of biochemical benefits. It has been found that they contribute in different health related problems. A wide range of commonly consumed foods contain appreciable amounts of phytoestrogens. Consumption of diet rich to phytoestrogen acts as a protective factor against many diseases such as cardiovascular diseases, post-menopausal symptoms in the context of osteoporosis, cancerous illnesses of colon, prostate and breast. Three main classes of phytoestrogens covers: isoflavones, lignans and coumestans. Selected nine major phytoestrogens had been analyzed simultaneously in the same foods. Questionnaire designed to determine intake frequency as well as amount of selected foods and the most common diseases presented in the population has been used to find relationships between dietary habits and health status. Evaluation of selected goals in the present study has been realized in cooperation with 140 respondents in retired age (divided into Males - covered by 34 individuals and Females - 106 individuals, comming from middle-north Slovakia region. On the base of collected data it can be concluded, that evaluated population is presented by high values of lignans intake and particularly secoisolariciresinol, mainly caused by relative high proportion of cereals and linseed in the diet. Furthermore, the relationship between phytoestrogens intake and eating habits as well as its contribution in protection against selected diseases was demonstrated. Normal 0 21 false false false CS JA X-NONE

  3. Cytoprotective and antioxidant effects of the methanol extract of ...

    African Journals Online (AJOL)

    Background: Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers. Materials and Methods: In this study, we tested the cytoprotective potential of the whole plant methanol extract (100-200 mg/kg, p.o), against ...

  4. Testicular cytoprotective activities of Curcuma longa in STZ-induced ...

    African Journals Online (AJOL)

    This study was aimed at investigating the cytoprotective activities of Curcuma longa (Turmeric) on the histological structure of the testes in diabetic male rats. Turmeric is commonly called the golden spice, is used as a spice in cooking and also has a long history of medicinal use, dating back nearly 4000 years to the Vedic ...

  5. Visual spatial memory is enhanced in female rats (but inhibited in males by dietary soy phytoestrogens

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    Setchell Kenneth DR

    2001-12-01

    Full Text Available Abstract Background In learning and memory tasks, requiring visual spatial memory (VSM, males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen. This study examined the influence of phytoestrogens (estrogen-like plant compounds on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB, and cyclooxygenase-2 (COX-2 levels were determined. Results Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600 acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free; in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified. Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum; in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease increased. Conclusions Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats.

  6. Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

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    Xueyan Chen

    2016-08-01

    Full Text Available Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.

  7. Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro.

    Science.gov (United States)

    Richter, Dagmar Ulrike; Mylonas, Ioannis; Toth, Bettina; Scholz, Christoph; Briese, Volker; Friese, Klaus; Jeschke, Udo

    2009-01-01

    Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study. Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production. The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed. Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.

  8. Phytoestrogens and Their Metabolites in Bulk-Tank Milk: Effects of Farm Management and Season

    DEFF Research Database (Denmark)

    Adler, Steffen A; Purup, Stig; Hansen-Møller, Jens

    2015-01-01

    Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare...... organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either...... short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often...

  9. Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis

    Science.gov (United States)

    Lee, Geum-A.; Hwang, Kyung-A.; Choi, Kyung-Chul

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy. PMID:27231938

  10. Phytoestrogens levels determination in the cord blood from Malaysia rural and urban populations

    International Nuclear Information System (INIS)

    Mustafa, A.M.; Malintan, N.T.; Seelan, S.; Zhan, Z.; Mohamed, Z.; Hassan, J.; Pendek, R.; Hussain, R.; Ito, N.

    2007-01-01

    This study is a result of an analysis of free and conjugated phytoestrogens daidzein, genistein, daidzin, genistin and coumesterol in human cord blood plasma using LCMS. Cord blood was collected from urban and rural populations of Malaysia (n = 300) to establish a simple preliminary database on the levels of the analyzed compounds in the collected samples. The study also aimed to look at the levels of phytoestrogens in babies during birth as this may have a profound effect on the developmental process. The sample clean up was carried out by solid-phase extraction using C18 column and passed through DEAE sephadex gel before analysis by LCMS. The mean concentrations of total phytoestrogens were daidzein (1.4 ± 2.9 ng/ml), genistein (3.7 ± 2.8 ng/ml), daidzin (3.5 ± 3.1 ng/ml), genistin (19.5 ± 4.2 ng/ml) and coumesterol (3.3 ± 3.3 ng/ml). Distribution of phytoestrogen was found to be higher in samples collected from rural areas compared to that of urban areas

  11. Phytoestrogens alter the reproductive organ development in the mink (Mustela vison)

    International Nuclear Information System (INIS)

    Ryoekkynen, Ari; Nieminen, Petteri; Mustonen, Anne-Mari; Pyykoenen, Teija; Asikainen, Juha; Haenninen, Sari; Mononen, Jaakko; Kukkonen, Jussi V.K.

    2005-01-01

    The aim of the present study was to examine the reproductive effects of two perorally applied phytoestrogens, genistein (8 mg/kg/day) and β-sitosterol (50 mg/kg/day), on the mink (Mustela vison) at human dietary exposure levels. Parental generations were exposed over 9 months to these phytoestrogens and their offspring were exposed via gestation and lactation. Parents and their offspring were sampled 21 days after the birth of the kits. Sex hormone levels, sperm quality, organ weights, and development of the kits were examined. The exposed females were heavier than the control females at the 1st postnatal day (PND). The control kits were heavier than the exposed kits from the 1st to the 21st PND. Phytoestrogens did not affect the organ weights of the adult minks, but the relative testicular weight of the exposed kits was higher than in the control kits. The relative prostate weight was higher and the relative uterine weight lower in the β-sitosterol-exposed kits than in the control kits. Moreover, the plasma dihydrotestosterone levels were lower in the genistein-exposed male kits compared to the control male kits. This study could not explain the mechanisms behind these alterations. The results indicate that perinatal phytoestrogen exposures cause alterations in the weight of the reproductive organs of the mink kits

  12. Identification and characterization of a phytoestrogen-specific gene from the MCF-7 human breast cancer cell

    International Nuclear Information System (INIS)

    Ramanathan, Lakshmi; Gray, Wesley G.

    2003-01-01

    Phytoestrogens are a group of compounds present in human diet that display estrogenic-like properties. Several studies have demonstrated that populations who consume large quantities of phytoestrogens have a reduced risk of estrogen-dependent cancers. Although it has been shown that certain phytoestrogens modulate estrogen action, their biological role in cancer reduction remains unclear. Through the use of differential display reverse transcriptase-polymerase chain reaction and representational difference analysis of cDNA, we have identified several phytoestrogen-responsive genes from the human breast cancer cell MCF-7. Two of these genes, PE-13.1 and pRDA-D, have been characterized in greater detail in this study. These genes were not previously known to be regulated by phytoestrogen or estradiol. PE-13.1 is a novel gene that specifies the coding of a 1.10-kb mRNA transcript. Northern blot analysis confirmed that the PE-13.1 transcript is up-regulated by phytoestrogens (Genistein, sevenfold; Zearalenone, twofold) and is nonresponsive to estradiol. Conversely, the pRDA-D transcript was down-regulated by both phytoestrogens and estradiol. The antiestrogen ICI-182,780 inhibits the expression of PE-13.1 and reverses the inhibition of pRDA-D expression induced by phytoestrogens and estradiol. Analysis of the tissue distribution of PE-13.1 transcript by RNA blot reveals that this transcript is expressed in both normal and tumor tissues. This report demonstrates for the first time the presence of two phytoestrogen-responsive genes that may be used as molecular markers in understanding the role dietary estrogen plays in cancer prevention

  13. Relationships between urinary biomarkers of phytoestrogens, phthalates, phenols, and pubertal stages in girls

    Directory of Open Access Journals (Sweden)

    Chakraborty TR

    2012-01-01

    Full Text Available Tandra R Chakraborty1, Eilliut Alicea1, Sanjoy Chakraborty21Department of Biology, Adelphi University, One South Avenue, Garden City; 2Department of Biological Sciences, New York City College of Technology, New York, NY, USAAbstract: Phytoestrogens, phthalates, and phenols are estrogen-disrupting chemicals that have a pronounced effect at puberty. They are exogenous chemicals that are either plant-derived or man-made, and can alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding, or cellular responses of natural estrogens. Phytoestrogens, phthalates, and phenols are some of the potent estrogens detectable in urine. Phytoestrogens are plant-derived xenestrogens found in a wide variety of food products, like soy-based food, beverages, several fruits, and vegetables. Exposure to phytoestrogens can delay breast development and further lead to precocious puberty. The effect of phytoestrogens is mediated through estrogen receptors α and β or by binding with early immediate genes, such as jun and fos. Phthalates are multifunctional synthetic chemicals used in plastics, polyvinyl chloride products, cosmetics, hair spray, and children's toys. Phthalates have been shown to cause defeminization, thelarche, precocious puberty, and an increase in breast and pubic hair in pubertal girls. However, reports are also available that show no association of phthalates with precocious puberty in girls. Phthalates can act through a receptor-mediated signaling pathway or affect the production of luteinizing hormone and follicle-stimulating hormone that has a direct effect on estrogen formation. Phenols like bisphenol A are industrial chemicals used mainly in the manufacture of polycarbonates and plastic materials. Bisphenol A has been shown to cause precocious puberty and earlier menarche in pubertal girls. Reports suggest that the neurotoxic effect of bisphenol A can be mediated either by

  14. Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

    Science.gov (United States)

    2009-01-01

    Background Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids. Methods Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3 - 4 mg/kg/day) for ~3 months. Plasma testosterone and total and free triiodothyronine (T3) concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA) was carried out. Results No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8) phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l). This elevation was preceded by a rise in plasma total T3 that occurred on September 17 (week 6). A slightly higher concentration of free T3 was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10) that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant. Conclusion Our findings suggest that phytoestrogens can stimulate testosterone synthesis during puberty in

  15. Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3 levels in male goat kids

    Directory of Open Access Journals (Sweden)

    Ekstedt Elisabeth

    2009-12-01

    Full Text Available Abstract Background Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids. Methods Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3 - 4 mg/kg/day for ~3 months. Plasma testosterone and total and free triiodothyronine (T3 concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA was carried out. Results No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8 phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l. This elevation was preceded by a rise in plasma total T3 that occurred on September 17 (week 6. A slightly higher concentration of free T3 was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10 that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant. Conclusion Our findings suggest that phytoestrogens can stimulate testosterone

  16. Isolation and identification of phytoestrogens and flavonoids in an Ayurvedic proprietary medicine using chromatographic and Mass Spectroscopic analysis

    Institute of Scientific and Technical Information of China (English)

    Sulaiman CT; Arun A; Anandan EM; Sandhya CR; Indira Balachandran

    2015-01-01

    Objective: To develop analytical methods for the isolation and structural identification of poly phenols including phytoestrogens in Mensokot tablet, a herbal proprietary medicine. Methods:Isolation consisted of an ultrasound-assisted extraction, followed by acid hydrolysis and a final liquid-liquid extraction step in diethyl ether. Identification and structural characterisation was done by liquid chromatography coupled with Q-TOF-ESI-MS/MS analysis. Results:Phytoestrogens such as Coumestrol, Genistein and Glycitein have been identified in Mensokot tablet along with several other flavonoids. Conclusion: In the present research, a rapid HPLC-MS/MS method has been developed for the identification of phytoestrogens and other flavonoids from an Ayurvedic proprietary medicine. Phytoestrogens are considered to play an important role in the prevention of cancers, heart disease, menopausal symptoms and osteoporosis.

  17. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  18. Phytoestrogens and Their Metabolites in Bulk-Tank Milk: Effects of Farm Management and Season

    Science.gov (United States)

    Adler, Steffen A.; Purup, Stig; Hansen-Møller, Jens; Thuen, Erling; Steinshamn, Håvard

    2015-01-01

    Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG) was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of phytoestrogens

  19. Phytoestrogens and their metabolites in bulk-tank milk: effects of farm management and season.

    Directory of Open Access Journals (Sweden)

    Steffen A Adler

    Full Text Available Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L. in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of

  20. Effects of feeding dairy cows different legume-grass silages on milk phytoestrogen concentration

    DEFF Research Database (Denmark)

    Höjer, A; Adler, S; Purup, Stig

    2012-01-01

    interval of legume-grass silage on phytoestrogen intake and milk phytoestrogen concentrations. In one experiment, 15 Swedish Red dairy cows were fed 2- or 3-cut red clover-grass silage, or 2-cut birdsfoot trefoil-grass silage. In a second experiment, 16 Norwegian Red dairy cows were fed short-term ley...... red clover-grass silage diet (1,494μg/kg of milk). Because of the metabolism of biochanin A, genistein, and prunetin, their concentrations in milk and the apparent recovery were low. Coumestrol was detected in only short-term and long-term ley silage mixtures, and its milk concentration was low....... Concentrations of secoisolariciresinol and matairesinol were higher in 2-cut birdsfoot trefoil-grass and long-term ley silage mixtures, those with legume species other than red clover, and the highest grass proportions. The 2-cut birdsfoot trefoil-grass silage diet also resulted in higher enterolactone...

  1. Anti-inflammatory and neuroprotective effect of a phytoestrogen compound on rat microglia.

    Science.gov (United States)

    Marotta, F; Mao, G S; Liu, T; Chui, D H; Lorenzetti, A; Xiao, Y; Marandola, P

    2006-11-01

    Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.

  2. Effects of phytoestrogens derived from soy bean on expression of adhesion molecules on HUVEC.

    Science.gov (United States)

    Andrade, C M de; Sá, M F Silva de; Toloi, M R Torqueti

    2012-04-01

    The risks of hormone replacement therapy have led to a search for new alternatives such as phytoestrogens, plant compounds with estrogen-like biological activity. Isoflavones are the phytoestrogens most extensively studied and can be found in soybean, red clover and other plants. Due to this estrogen-like activity, phytoestrogens can have some effect on atherosclerosis. Human umbilical vein endothelial cells (HUVEC) have been extensively used to study the biology and pathobiology of human endothelial cells and most of the knowledge acquired is due to experiments with cultures of these cells. To evaluate the effects of the phytoestrogen extracts from Glycine max soy bean, genistein, formononetin, biochanin A and daidzein, as well as a mixture of these extracts (Mix), on expression of adhesion molecules, VCAM-1, ICAM-1 and E-selectin, by endothelial cell HUVEC, stimulated with lipopolysaccharide. HUVEC were cultured in medium EBM(2), pretreated with isoflavones for 24 and 48 h and then stimulated with lipopolysaccharide; in addition, isoflavones were added, after stimulation by lipopolysaccharide, to HUVEC. We evaluated the production of VCAM-1, ICAM-1 and E-selectin on cell surface, by cell-based enzyme immunoassay, and of sVCAM-1, sICAM-1 and sE-selectin in culture supernatant, by ELISA. Genistein, formononetin, biochanin A and daidzein, as well as the Mix were able to reduce VCAM-1, ICAM-1 and E-selectin on cell surface and in culture supernatant. Conclusion Isoflavones extracted from Glycine max soy bean, in vitro, presented antiatherogenic effects, reducing the expression of adhesion molecules and acting as preventive agents as well as therapeutic agents.

  3. Phytoestrogens and mycotoxins in Iowa streams: An examination of underinvestigated compounds in agricultural basins

    Science.gov (United States)

    Kolpin, Dana W.; Hoerger, Corinne C.; Meyer, Michael T.; Wettstein, Felix E.; Hubbard, Laura E.; Bucheli, Thomas D.

    2010-01-01

    This study provides the first broad-scale investigation on the spatial and temporal occurrence of phytoestrogens and mycotoxins in streams in the United States. Fifteen stream sites across Iowa were sampled five times throughout the 2008 growing season to capture a range of climatic and crop-growth conditions. Basin size upstream from sampling sites ranged from 7 km2 to >836,000 km2 Atrazine (herbicide) also was measured in all samples as a frame-of-reference agriculturally derived contaminant. Target compounds were frequently detected in stream samples: atrazine (100%), formononetin (80%), equol (45%), deoxynivalenol (43%), daidzein (32%), biochanin A (23%), zearalenone (13%), and genistein (11%). The nearly ubiquitous detection of formononetin (isoflavone) suggests a widespread agricultural source, as one would expect with the intense row crop and livestock production present across Iowa. Conversely, the less spatially widespread detections of deoxynivalenol (mycotoxin) suggest a more variable source due to the required combination of proper host and proper temperature and moisture conditions necessary to promote Fusarium spp. infections. Although atrazine concentrations commonly exceeded 100 ng L-1 (42/75 measurements), only deoxynivalenol (6/56 measurements) had concentrations that occasionally exceeded this level. Temporal patterns in concentrations varied substantially between atrazine, formononetin, and deoxynivalenol, as one would expect for contaminants with different source inputs and processes of formation and degradation. The greatest phytoestrogen and mycotoxin concentrations were observed during spring snowmelt conditions. Phytoestrogens and mycotoxins were detected at all sampling sites regardless of basin size. The ecotoxicological effects from long-term, low-level exposures to phytoestrogens and mycotoxins or complex chemicals mixtures including these compounds that commonly take place in surface water are poorly understood and have yet to be

  4. Comprehensive assessment of hormones, phytoestrogens, and estrogenic activity in an anaerobic swine waste lagoon

    Science.gov (United States)

    Yost, Erin E.; Meyer, Michael T.; Dietze, Julie E.; Meissner, Benjamin M.; Williams, Mike; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W.

    2013-01-01

    In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge were assessed using LC/MS-MS, and yeast estrogen screen was used to determine estrogenic activity. Of the hormone analytes, steroidal estrogens were more abundant than androgens or progesterone, with estrone being the predominant estrogen species. Conjugated hormones were detected only at low levels. The isoflavone metabolite equol was by far the predominant phytoestrogen species, with daidzein, genistein, formononetin, and coumestrol present at lower levels. Phytoestrogens were often more abundant than steroidal estrogens, but contributed minimally towards total estrogenic activity. Analytes were significantly elevated in the solid phases of the lagoon; although low observed log KOC values suggest enhanced solubility in the aqueous phase, perhaps due to dissolved or colloidal organic carbon. The association with the solid phase, as well as recalcitrance of analytes to anaerobic degradation, results in a markedly elevated load of analytes and estrogenic activity within lagoon sludge. Overall, findings emphasize the importance of adsorption and transformation processes in governing the fate of these compounds in lagoon waste, which is ultimately used for broadcast application as a fertilizer.

  5. Transport of steroid hormones, phytoestrogens, and estrogenic activity across a swine lagoon/sprayfield system.

    Science.gov (United States)

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Williams, C Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W

    2014-10-07

    The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.

  6. Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

    Directory of Open Access Journals (Sweden)

    Roxana N. Peroni

    2012-01-01

    Full Text Available In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses. It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

  7. Using vaginal cytology to assess the estrogenic activity of phytoestrogen-rich herb.

    Science.gov (United States)

    Malaivijitnond, Suchinda; Chansri, Kullakanya; Kijkuokul, Pisamai; Urasopon, Nontakorn; Cherdshewasart, Wichai

    2006-10-11

    To assess the estrogenic activities of synthetic estrogen, synthetic phytoestrogen, Pueraria lobata and three distinct cultivars of Pueraria mirifica, a phytoestrogen-rich herb, a vaginal cytology assay in ovariectomized rats were used. Rats were ovariectomized and treated with DW, estradiol valerate (1 mg/kg BW), genistein (0.25-2.5 mg/kg BW), Pueraria lobata and Pueraria mirifica (10-1,000 mg/kg BW) for 14 days. The vaginal cytology was checked daily and the uteri were dissected and weighed at the end of treatment or post-treatment periods. The treatments of DW, genistein and Pueraria lobata did not influence the vaginal epithelium, but the injection of estradiol valerate induced a vaginal cornification from day-3 of treatment to day-14 of post-treatment period. The occurrence of vaginal cornification after treatment and the recovery after the cessation was dependent on dosages and cultivars of Pueraria mirifica. The increments of uterus weight in all rats agreed with the cornification of vaginal epithelium. Although both uterotropic and vaginal cytology assays can be used to assess the estrogenic activity of phytoestrogen-rich herb, however, using vaginal cytology assay has two advantages: (1) we do not need to kill the animals and (2) we can follow up the recovery after the cessation of treatment.

  8. 17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.

    2001-01-01

    The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.20% nari...... and its antiatherogenic effect. - Mortensen, A., V. Breinholt, T. Dalsgaard, H. Frandsen, S. T. Lauridsen, J. Laigaard, B. Ottesen, and J-J. Larsen. 17 beta -Estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits.......The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.......20% naringenin, for 16 weeks. The uterine weight was increased (P 17 beta -E-2 group compared with the controls. Total plasma cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...

  9. Induction of cytoprotective autophagy in PC-12 cells by cadmium

    International Nuclear Information System (INIS)

    Wang, Qiwen; Zhu, Jiaqiao; Zhang, Kangbao; Jiang, Chenyang; Wang, Yi; Yuan, Yan; Bian, Jianchun; Liu, Xuezhong; Gu, Jianhong; Liu, Zongping

    2013-01-01

    Highlights: •Cadmium can promote early upregulation of autophagy in PC-12 cells. •Autophagy precedes apoptosis in cadmium-treated PC-12 cells. •Cadmium-induced autophagy is cytoprotective in PC-12 cells. •Class III PI3K/beclin-1/Bcl-2 signaling pathway plays a positive role in cadmium-triggered autophagy. -- Abstract: Laboratory data have demonstrated that cadmium (Cd) may induce neuronal apoptosis. However, little is known about the role of autophagy in neurons. In this study, cell viability decreased in a dose- and time-dependent manner after treatment with Cd in PC-12 cells. As cells were exposed to Cd, the levels of LC3-II proteins became elevated, specific punctate distribution of endogenous LC3-II increased, and numerous autophagosomes appeared, which suggest that Cd induced a high level of autophagy. In the late stages of autophagy, an increase in the apoptosis ratio was observed. Likewise, pre-treatment with chloroquine (an autophagic inhibitor) and rapamycin (an autophagic inducer) resulted in an increased and decreased percentage of apoptosis in contrast to other Cd-treated groups, respectively. The results indicate that autophagy delayed apoptosis in Cd-treated PC-12 cells. Furthermore, co-treatment of cells with chloroquine reduced autophagy and cell activity. However, rapamycin had an opposite effect on autophagy and cell activity. Moreover, class III PI3 K/beclin-1/Bcl-2 signaling pathways served a function in Cd-induced autophagy. The findings suggest that Cd can induce cytoprotective autophagy by activating class III PI3 K/beclin-1/Bcl-2 signaling pathways. In sum, this study strongly suggests that autophagy may serve a positive function in the reduction of Cd-induced cytotoxicity

  10. Dietary Phytoestrogen Intake is Inversely Associated with Hypertension in a Cohort of Adults Living in the Mediterranean Area

    Directory of Open Access Journals (Sweden)

    Justyna Godos

    2018-02-01

    Full Text Available Background: Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging. Methods: We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data included 1936 men and women aged 18 years and older. Intakes of total phytoestrogens, isoflavones, and lignans were calculated from validated food frequency questionnaire. Data on the polyphenols content in foods were retrieved from the Phenol-Explorer database. Results: Individuals in the highest quartile of dietary phytoestrogens intake were less likely to be hypertensive (OR: 0.66, 95% CI: 0.44–0.98; moreover, the association showed a significant decreasing trend. Isoflavones and lignans were not associated with lower odds of hypertension; however, some individual compounds, such as biochanin A and pinoresinol showed an independent inverse association with hypertension. Conclusions: Dietary phytoestrogens are associated with lower likelihood of hypertension in adults living in the Mediterranean area. Future studies are needed to confirm the present findings (i.e., prospective cohort studies and to better understand the mechanisms underlying such associations.

  11. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    International Nuclear Information System (INIS)

    Ohtomo, Tadashi; Miyazawa, Keisuke; Naito, Munekazu; Moriya, Shota; Kuroda, Masahiko; Itoh, Masahiro; Tomoda, Akio

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5 -/- MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  12. Evidence for the gastric cytoprotective effect of centrally injected agmatine.

    Science.gov (United States)

    Zádori, Zoltán S; Tóth, Viktória E; Fehér, Ágnes; Philipp, Kirsch; Németh, József; Gyires, Klára

    2014-09-01

    Agmatine (decarboxylated arginine) exerts cytoprotective action in several tissues, such as in the brain, heart or kidneys, but there is still controversy over the effects of agmatine on the gastric mucosa. The aim of the present study was to reveal the potential gastroprotective action of agmatine by using an acid-independent ulcer model to clarify which receptors and peripheral factors are involved in it. Gastric mucosal damage was induced by acidified ethanol. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. It was found that agmatine given intracerebroventricularly (i.c.v., 0.044-220 nmol/rat) significantly inhibited the development of ethanol-induced mucosal damage, while in the case of intraperitoneal injection (0.001-50mg/kg i.p.) it had only a minor effect. The central gastroprotective action of agmatine was completely antagonized by mixed alpha2-adrenoceptor and imidazoline I1 receptor antagonists (idazoxan, efaroxan), but only partially by yohimbine (selective alpha2-adrenoceptor antagonist) and AGN 192403 (selective I1 receptor ligand, putative antagonist). It was also inhibited by the non-selective opioid-receptor antagonist naloxone and the selective δ-opioid receptor antagonist naltrindole, but not by β-funaltrexamine and nor-Binaltorphimine (selective μ- and κ-opioid receptor antagonists, respectively). Furthermore, the effect of agmatine was antagonized by bilateral cervical vagotomy and by pretreatment with indomethacin and NG-nitro-l-arginine. Agmatine also reversed the ethanol-induced reduction of gastric mucosal CGRP and somatostatin content, but did not have any significant effect on gastric motor activity. These results indicate that agmatine given centrally induces gastric cytoprotection, which is mediated by central imidazoline I1 receptors, alpha2-adrenoceptors and δ-opioid receptors. Activation of

  13. The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study

    NARCIS (Netherlands)

    Zaineddin, A.K.; Buck, K.; Vrieling, A.; Heinz, J.; Flesch-Janys, D.; Linseisen, J.; Chang-Claude, J.

    2012-01-01

    Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women

  14. Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.

    Science.gov (United States)

    Hegedűs, Csaba; Lakatos, Petra; Kiss-Szikszai, Attila; Patonay, Tamás; Gergely, Szabolcs; Gregus, Andrea; Bai, Péter; Haskó, György; Szabó, Éva; Virág, László

    2013-06-01

    Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity. From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly(ADP-ribosyl)ation (PARylation), a cytotoxic pathway operating in severely injured cells. Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation. These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected. Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK). The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38. Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific. In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly(ADP-ribose) polymerase inhibition. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

    Science.gov (United States)

    Li, Xia; Jiang, Xinwei; Sun, Jianxia; Zhu, Cuijuan; Li, Xiaoling; Tian, Lingmin; Liu, Liu; Bai, Weibin

    2017-06-01

    Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported. © 2017 New York Academy of Sciences.

  16. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  17. Effects of phytoestrogen supplementation in postmenopausal women with dry eye syndrome: a randomized clinical trial.

    Science.gov (United States)

    Scuderi, Gianluca; Contestabile, Maria Teresa; Gagliano, Caterina; Iacovello, Daniela; Scuderi, Luca; Avitabile, Teresio

    2012-12-01

    To evaluate the correlation between tear osmolarity and blood levels of 17-β estradiol, estrone, and testosterone in postmenopausal women with dry eye syndrome, and to assess the efficacy and safety of oral supplementation with phytoestrogens, lipoic acid, and eicosapentaenoic acid in this population. Cross-sectional study including 66 postmenopausal women with dry eye syndrome. Sixty-six postmenopausal women with dry eye syndrome were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients were divided into 2 groups (groups A and B) and treated, respectively, with phytoestrogen (Bioos, Montegiorgio, Italy) tablets or placebo tablets for 30 days. The 2 treatment periods were separated by a 30-day washout. Patients were examined on days 0 and 30 of each period. Assessments included blood levels of sex hormones, the Schirmer test for tear production, and measurement of tear osmolarity and tear film break-up time. At baseline, all patients had low sex hormone levels, which were correlated with high tear film osmolarity values (r = -0.59,-0.61,-0.58, respectively). After 30 days of therapy, the group treated with Lacrisek® (Bioos) had significantly decreased tear osmolarity (Pdry eye syndrome in postmenopausal women. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  18. Coumestrol and its metabolite in mares' plasma after ingestion of phytoestrogen-rich plants: potent endocrine disruptors inducing infertility.

    Science.gov (United States)

    Ferreira-Dias, G; Botelho, M; Zagrajczuk, A; Rebordão, M R; Galvão, A M; Bravo, P Pinto; Piotrowska-Tomala, K; Szóstek, A Z; Wiczkowski, W; Piskula, M; Fradinho, M J; Skarzynski, D J

    2013-10-01

    Phytoestrogens exist in plants that are present in forages fed to horses. They may compete with 17-β estradiol and influence the estrous cycle. Therefore, the objective was to determine whether coumestrol from clover-mixed pastures is present in mare's plasma after their ingestion (experiment I), and when this phytoestrogen was present in mare's plasma after ingestion (experiment II). The effect of a long-term ingestion of phytoestrogens on estrous cycle disruption was assessed (experiment III; clinical case). Experiment I was carried out in nonpregnant anestrous and cyclic Lusitano mares (n = 14) kept on clover and grass-mixed pastures, and supplemented with concentrate and hay or cereal straw. Blood and feedstuff were obtained from November to March. In experiment II, stabled cyclic Lusitano mares (n = 6) were fed for 14 days with increasing amounts of alfalfa pellets (250 g to 1 kg/day). Sequential blood samples were obtained for 8 hours after feed intake on Day 0 (control) and on Days 13 and 14 (1 kg/day alfalfa pellets). Experiment III mares were fed with a mixture of alfalfa and clover haylage for 5 months (group 1; n = 4) or for 9 months (group 2; n = 12). Estrous cycle was determined on the basis of plasma estradiol (E2), progesterone (P4), and ultrasound (experiment III). Concentrations of phytoestrogen coumestrol and its metabolite methoxycoumestrol were determined by high-performance liquid chromatography coupled with mass spectrometry. Phytoestrogens decreased in pasture from November until March (P haylage) than in group 1, after haylage withdrawal (P < 0.001). These data show that in the mare, coumestrol and its metabolite increase in blood after ingestion of estrogenic plants and can influence reproduction in mares as potent endocrine disruptors. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The Improvement of Hypertension by Probiotics: Effects on Cholesterol, Diabetes, Renin, and Phytoestrogens

    Directory of Open Access Journals (Sweden)

    Huey-Shi Lye

    2009-08-01

    Full Text Available Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.

  20. Improvements of insulin resistance in ovariectomized rats by a novel phytoestrogen from Curcuma comosa Roxb

    Directory of Open Access Journals (Sweden)

    Prasannarong Mujalin

    2012-03-01

    Full Text Available Abstract Background Curcuma comosa Roxb. (C. comosa is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3R-1,7-diphenyl-(4E,6E-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of C. comosa in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks of C. comosa hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats. Methods Female Sprague-Dawley rats were ovariectomized (OVX and treated with C. comosa hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW and compound 049 (50 mg/kg BW intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined. Results Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with C. comosa hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of C. comosa hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels. Conclusions Treatment with C. comosa and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.

  1. Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily.

    Science.gov (United States)

    Russo, Giorgio I; Di Mauro, Marina; Regis, Federica; Reale, Giulio; Campisi, Daniele; Marranzano, Marina; Lo Giudice, Arturo; Solinas, Tatiana; Madonia, Massimo; Cimino, Sebastiano; Morgia, Giuseppe

    2018-03-01

    In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.

  2. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis--A Pilot Study.

    Science.gov (United States)

    Aboodi, Guy M; Sima, Corneliu; Moffa, Eduardo B; Crosara, Karla T B; Xiao, Yizhi; Siqueira, Walter L; Glogauer, Michael

    2015-01-01

    The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active.

  3. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis—A Pilot Study

    Science.gov (United States)

    Aboodi, Guy M.; Sima, Corneliu; Moffa, Eduardo B.; Crosara, Karla T. B.; Xiao, Yizhi; Siqueira, Walter L.; Glogauer, Michael

    2016-01-01

    Objective: The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. Study design: We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Results: Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Conclusions: Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. Clinical relevance: We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active. PMID:26779447

  4. Cytoprotective effect of recombinant human erythropoietin produced in transgenic tobacco plants.

    Directory of Open Access Journals (Sweden)

    Farooqahmed S Kittur

    Full Text Available Asialo-erythropoietin, a desialylated form of human erythropoietin (EPO lacking hematopoietic activity, is receiving increased attention because of its broader protective effects in preclinical models of tissue injury. However, attempts to translate its protective effects into clinical practice is hampered by unavailability of suitable expression system and its costly and limit production from expensive mammalian cell-made EPO (rhuEPO(M by enzymatic desialylation. In the current study, we took advantage of a plant-based expression system lacking sialylating capacity but possessing an ability to synthesize complex N-glycans to produce cytoprotective recombinant human asialo-rhuEPO. Transgenic tobacco plants expressing asialo-rhuEPO were generated by stably co-expressing human EPO and β1,4-galactosyltransferase (GalT genes under the control of double CaMV 35S and glyceraldehyde-3-phosphate gene (GapC promoters, respectively. Plant-produced asialo-rhuEPO (asialo-rhuEPO(P was purified by immunoaffinity chromatography. Detailed N-glycan analysis using NSI-FTMS and MS/MS revealed that asialo-rhuEPO(P bears paucimannosidic, high mannose-type and complex N-glycans. In vitro cytoprotection assays showed that the asialo-rhuEPO(P (20 U/ml provides 2-fold better cytoprotection (44% to neuronal-like mouse neuroblastoma cells from staurosporine-induced cell death than rhuEPO(M (21%. The cytoprotective effect of the asialo-rhuEPO(P was found to be mediated by receptor-initiated phosphorylation of Janus kinase 2 (JAK2 and suppression of caspase 3 activation. Altogether, these findings demonstrate that plants are a suitable host for producing cytoprotective rhuEPO derivative. In addition, the general advantages of plant-based expression system can be exploited to address the cost and scalability issues related to its production.

  5. Model of personalised risk assessment of phytoestrogen intake based on 11 SNP in ESR1 and ESR2 genes

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    Radoslav Zidek

    2016-12-01

    Full Text Available Phytoestrogens can induce biological responses in vertebrates by mimicking or modulating the action or production of endogenous hormones, and because of their structural similarity with estradiol they have the ability to cause estrogenic or anti-estrogenic effects. Risk assessment of phytoestrogens intake may therefore provide important information useful in the adjustment of nutrients composition, as one of nutrigenomics approaches. Proper risk assessment is an essential part of good nutrient composition. The current risk assessment procedures does use an additive effect of genes, but the accumulation of relevant factors do not count with the distribution of risk in the European population. A combination of approaches based on genetic score, along with the use of the data bases like 1000 genomes and dbSNP is a powerful tool for population risk modelling that would provide reasonable results without needs of as testing a representative number of individual genetic profiles.

  6. Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US.

    Science.gov (United States)

    Martínez Steele, Eurídice; Monteiro, Carlos A

    2017-02-28

    The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009-2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence "ultra-processed"). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O -desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans.

  7. Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US

    Directory of Open Access Journals (Sweden)

    Eurídice Martínez Steele

    2017-02-01

    Full Text Available The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009–2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants. Food items were classified according to NOVA (a name, not an acronym, a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence “ultra-processed”. Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol and isoflavones (genistein, daidzein, O-desmethylangolensin and equol. Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans.

  8. Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Li Zhuoneng

    2010-09-01

    Full Text Available Abstract Background Estrogen or phytoestrogens treatment has been suggested to improve cognitive function of the brain in postmenopausal women. However, there is lack of information on the mechanism of such treatment on the central nervous system. The present study aimed to determine the effects of estradiol and soy germ phytoestrogens on spatial memory performance in ovariectomized rats and to explore the underlying mechanisms affecting the central nervous system. Methods Ovariectomized Sprague-Dawley rats were fed a basic diet supplemented with soy germ phytoestrogens (0.4 g/kg or 1.6 g/kg or 17β-estradiol (0.15 g/kg for 12 weeks. At the end of the experiment, animals were evaluated for their spatial learning and memory performance by the Morris Water Maze task. The expressions of brain-derived neurotrophic factor (BDNF and synaptic formation proteins in the hippocampal tissue were estimated using RT-PCR and ELISA. Results It was found that rats supplemented with soy germ phytoestrogens or estradiol performed significantly better in spatial memory acquisition and retention when compared to the rats fed on the control diet. Estradiol or the high dose of phytoestrogens treatment significantly increased BDNF concentration and the mRNA levels for BDNF and its TrkB receptors as well as the synaptic formation proteins, synaptophysin, spinophilin, synapsin 1 and PSD-95, in the hippocampal tissue of the experimental animals. It was also found that phytoestrogens, in contrast to estradiol, did not show any significant effect on the vaginal and uteri. Conclusion Soy germ phytoestrogens, which may be a substitute of estradiol, improved spatial memory performance in ovariectomized rats without significant side-effects on the vaginal and uteri. The memory enhancement effect may relate to the increase in BDNF and the synaptic formation proteins expression in the hippocampus of the brain.

  9. Antiradical and cytoprotective activities of several C-geranyl-substituted flavanones from Paulownia tomentosa fruit.

    Science.gov (United States)

    Zima, Ales; Hosek, Jan; Treml, Jakub; Muselík, Jan; Suchý, Pavel; Prazanová, Gabriela; Lopes, Ana; Zemlicka, Milan

    2010-08-31

    Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

  10. Effects of Vehicles and Enhancers on the Skin Permeation of Phytoestrogenic Diarylheptanoids from Curcuma comosa.

    Science.gov (United States)

    Tuntiyasawasdikul, Sarunya; Limpongsa, Ekapol; Jaipakdee, Napaphak; Sripanidkulchai, Bungorn

    2017-04-01

    Curcuma comosa (C. comosa) is widely used in traditional medicine as a dietary supplement for health promotion in postmenopausal women in Thailand. It contains several diarylheptanoids, which are considered to be a novel class of phytoestrogens. However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics. The aim of this study was to investigate the permeation behavior of the active compounds of diarylheptanoids. The effects of binary vehicle systems and permeation enhancers on diarylheptanoids permeation and accumulation within the skin were studied using side-by-side diffusion cells through the porcine ear skin. Among the tested binary vehicle systems, the ethanol/water vehicle appeared to be the most effective system for diarylheptanoids permeation with the highest flux and shortest lag time. The presence of transcutol in the vehicle system significantly increased diarylheptanoid's permeation and accumulation within the skin in a concentration-dependent manner. Although the presence of terpenes in formulation decreased the flux of diarylheptanoids, it raised the amount of diarylheptanoids retained within the skin substantially. Based on the feasibility of diarylheptanoid permeation, C. comosa extract should be further developed into an effective transdermal product for health benefits and hormone replacement therapy.

  11. The fate of pharmaceuticals, steroid hormones, phytoestrogens, UV-filters and pesticides during MBR treatment.

    Science.gov (United States)

    Wijekoon, Kaushalya C; Hai, Faisal I; Kang, Jinguo; Price, William E; Guo, Wenshan; Ngo, Hao H; Nghiem, Long D

    2013-09-01

    This study examined the relationship between molecular properties and the fate of trace organic contaminants (TrOCs) in the aqueous and solid phases during wastewater treatment by MBR. A set of 29 TrOCs was selected to represent pharmaceuticals, steroid hormones, phytoestrogens, UV-filters and pesticides that occur ubiquitously in municipal wastewater. Both adsorption and biodegradation/transformation were found responsible for the removal of TrOCs by MBR treatment. A connection between biodegradation and molecular structure could be observed while adsorption was the dominant removal mechanism for the hydrophobic (logD>3.2) compounds. Highly hydrophobic (logD>3.2) but readily biodegradable compounds did not accumulate in sludge. In contrast, recalcitrant compounds with a moderate hydrophobicity, such as carbamazepine, accumulated significantly in the solid phase. The results provide a framework to predict the removal and fate of TrOCs by MBR treatment. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  12. Differential binding with ERα and ERβ of the phytoestrogen-rich plant Pueraria mirifica

    Directory of Open Access Journals (Sweden)

    C. Boonchird

    2010-02-01

    Full Text Available Variations in the estrogenic activity of the phytoestrogen-rich plant, Pueraria mirifica, were determined with yeast estrogen screen (YES consisting of human estrogen receptors (hER hERα and hERβ and human transcriptional intermediary factor 2 (hTIF2 or human steroid receptor coactivator 1 (hSRC1, respectively, together with the β-galactosidase expression cassette. Relative estrogenic potency was expressed by determining the β-galactosidase activity (EC50 of the tuber extracts in relation to 17β-estradiol. Twenty-four and 22 of the plant tuber ethanolic extracts interacted with hERα and hERβ, respectively, with a higher relative estrogenic potency with hERβ than with hERα. Antiestrogenic activity of the plant extracts was also determined by incubation of plant extracts with 17β-estradiol prior to YES assay. The plant extracts tested exhibited antiestrogenic activity. Both the estrogenic and the antiestrogenic activity of the tuber extracts were metabolically activated with the rat liver S9-fraction prior to the assay indicating the positive influence of liver enzymes. Correlation analysis between estrogenic potency and the five major isoflavonoid contents within the previously HPLC-analyzed tuberous samples namely puerarin, daidzin, genistin, daidzein, and genistein revealed a negative result.

  13. Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

    Directory of Open Access Journals (Sweden)

    Mingyue Zhang

    2015-11-01

    Full Text Available Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256 collected from children in China were measured by liquid chromatography (LC-tandem mass spectrometry (MS/MS. Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

  14. Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.

    Directory of Open Access Journals (Sweden)

    Kangkai Wang

    Full Text Available Mipu1 (myocardial ischemic preconditioning up-regulated protein 1, recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2 treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.

  15. Soy and other legumes: 'Bean' around a long time but are they the 'superfoods' of the millennium and what are the safety issues for their constituent phytoestrogens?

    Science.gov (United States)

    Setchell, K D; Radd, S

    2000-09-01

    The recognition that legumes and, in particular, soybeans provide not only an excellent source of vegetable protein but also contain appreciable amounts of a number of phytoprotectants has increased general awareness of their potential nutritional and health properties. Since the discovery that soybeans are one of the richest dietary sources of bioavailable phytoestrogens, this legume has been elevated to the forefront of clinical nutritional research. These natural 'selective oestrogen receptor modulators' have been shown to be bioactive. The recent approval by the Food and Drug Administration in the United States for a health claim for soy protein reducing risk for heart disease by its effects on lowering cholesterol levels has led to the increased awareness of the health benefits of soy protein. However, the presence of high levels of phytoestrogens in soybeans has also led to concerns over the potential safety of soy foods. This review will focus on the cardioprotective benefits of legumes and discuss the hypothetical concerns regarding the constituent phytoestrogens.

  16. Multiclass analytical method for the determination of natural/synthetic steroid hormones, phytoestrogens, and mycoestrogens in milk and yogurt.

    Science.gov (United States)

    Socas-Rodríguez, Bárbara; Lanková, Darina; Urbancová, Kateřina; Krtková, Veronika; Hernández-Borges, Javier; Rodríguez-Delgado, Miguel Ángel; Pulkrabová, Jana; Hajšlová, Jana

    2017-07-01

    Within this study, a new method enabling monitoring of various estrogenic substances potentially occurring in milk and dairy products was proposed. Groups of compounds fairly differing in physico-chemical properties and biological activity were analyzed: four natural estrogens, four synthetic estrogens, five mycoestrogens, and nine phytoestrogens. Since they may pass into milk mainly in glucuronated and sulfated forms, an enzymatic hydrolysis was involved prior to the extraction based on the QuEChERS methodology. For the purification of the organic extract, a dispersive solid-phase extraction (d-SPE) with sorbent C18 was applied. The final analysis was performed by ultra-high-performance liquid chromatography (UHPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS). Method recovery ranged from 70 to 120% with a relative standard deviation (RSD) value lower than 20% and limits of quantification (LOQs) in the range of 0.02-0.60 μg/L (0.2-6.0 μg/kg dry weight) and 0.02-0.90 μg/kg (0.2-6.0 μg/kg dry weight) for milk and yogurt, respectively. The new procedure was applied for the investigation of estrogenic compounds in 11 milk samples and 13 yogurt samples from a Czech retail market. Mainly phytoestrogens were found in the studied samples. The most abundant compounds were equol and enterolactone representing 40-90% of all estrogens. The total content of phytoestrogens (free and bound) was in the range of 149-3870 μg/kg dry weight. This amount is approximately 20 times higher compared to non-bound estrogens.

  17. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

    Science.gov (United States)

    Marini, Herbert; Minutoli, Letteria; Polito, Francesca; Bitto, Alessandra; Altavilla, Domenica; Atteritano, Marco; Gaudio, Agostino; Mazzaferro, Susanna; Frisina, Alessia; Frisina, Nicola; Lubrano, Carla; Bonaiuto, Michele; D'Anna, Rosario; Cannata, Maria Letizia; Corrado, Francesco; Adamo, Elena Bianca; Wilson, Steven; Squadrito, Francesco

    2007-06-19

    Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Randomized, double-blind, placebo-controlled trial. 3 university medical centers in Italy. 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P power to evaluate adverse effects. Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.

  18. Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women.

    Science.gov (United States)

    Teas, Jane; Hurley, Thomas G; Hebert, James R; Franke, Adrian A; Sepkovic, Daniel W; Kurzer, Mindy S

    2009-05-01

    Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.

  19. The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid

    Science.gov (United States)

    Zhou, Yong; Doyen, Rand; Lichtenberger, Lenard M.

    2013-01-01

    In cholestatic liver diseases, the ability of hydrophobic bile acids to damage membranes of hepatocytes/ductal cells contributes to their cytotoxicity. However, ursodeoxycholic acid (UDC), a hydrophilic bile acid, is used to treat cholestasis because it protects membranes. It has been well established that bile acids associate with and solubilize free cholesterol (CHOL) contained within the lumen of the gallbladder because of their structural similarities. However, there is a lack of understanding of how membrane CHOL, which is a well-established membrane stabilizing agent, is involved in cytotoxicity of hydrophobic bile acids and the cytoprotective effect of UDC. We utilized phospholipid liposomes to examine the ability of membrane CHOL to influence toxicity of individual bile acids, such as UDC and the highly toxic sodium deoxycholate (SDC), as well as the cytoprotective mechanism of UDC against SDC-induced cytotoxicity by measuring membrane permeation and intramembrane dipole potential. The kinetics of bile acid solubilization of phosphatidylcholine liposomes containing various levels of CHOL was also characterized. It was found that the presence of CHOL in membranes significantly reduced the ability of bile acids to damage synthetic membranes. UDC effectively prevented damaging effects of SDC on synthetic membranes only in the presence of membrane CHOL, while UDC enhances the damaging effects of SDC in the absence of CHOL. This further demonstrates that the cytoprotective effects of UDC depend upon the level of CHOL in the lipid membrane. Thus, changes in cell membrane composition, such as CHOL content, potentially influence the efficacy of UDC as the primary drug used to treat cholestasis. PMID:19150330

  20. Cytoprotective effect of tocopherols in hepatocytes cultured with polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.

    1994-01-01

    When highly unsaturated fatty acids are added to cell cultures, it can become important to include antioxidants in the culture medium to prevent cytotoxic peroxidation. To find an optimal antioxidant for this purpose, the effect of 50 µM a-tocopherol, ¿-tocopherol, a-tocopheryl acetate, a...... of thiobarbituric acid reactive substances in the cultures was also measured. a-Tocopheryl acid succinate was found to be the most effective cytoprotective compound, followed by N,N'-diphenyl-1,4-phenylenediamine, a- tocopherol, ¿-tocopherol and a-tocopheryl acetate, and a-tocopheryl phosphate was without effect....

  1. Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sangsoo Daniel; Antenos, Monica [Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Squires, E. James [Department of Animal and Poultry Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Kirby, Gordon M., E-mail: gkirby@uoguelph.ca [Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)

    2013-07-15

    Bilirubin (BR) has recently been identified as the first endogenous substrate for cytochrome P450 2A5 (CYP2A5) and it has been suggested that CYP2A5 plays a major role in BR clearance as an alternative mechanism to BR conjugation by uridine-diphosphate glucuronyltransferase 1A1. This study investigated the mechanisms of Cyp2a5 gene regulation by BR and the cytoprotective role of CYP2A5 in BR hepatotoxicity. BR induced CYP2A5 expression at the mRNA and protein levels in a dose-dependent manner in primary mouse hepatocytes. BR treatment also caused nuclear translocation of Nuclear factor-E2 p45-related factor 2 (Nrf2) in hepatocytes. In reporter assays, BR treatment of primary hepatocytes transfected with a Cyp2a5 promoter-luciferase reporter construct resulted in a 2-fold induction of Cyp2a5 reporter activity. Furthermore, cotransfection of the hepatocytes with a Nrf2 expression vector without BR treatment resulted in an increase in Cyp2a5 reporter activity of approximately 2-fold and BR treatment of Nrf2 cotransfectants further increased reporter activity by 4-fold. In addition, site-directed mutation of the ARE in the reporter construct completely abolished both the BR- and Nrf2-mediated increases in reporter activity. The cytoprotective role of CYP2A5 against BR-mediated apoptosis was also examined in Hepa 1–6 cells that lack endogenous CYP2A5. Transient overexpression of CYP2A5 partially blocked BR-induced caspase-3 cleavage in Hepa 1–6 cells. Furthermore, in vitro degradation of BR was increased by microsomes from Hepa 1–6 cells overexpressing CYP2A5 compared to control cells transfected with an empty vector. Collectively, these results suggest that Nrf2-mediated CYP2A5 transactivation in response to BR may provide an additional mechanism for adaptive cytoprotection against BR hepatotoxicity. - Highlights: • The mechanism of Cyp2a5 gene regulation by BR was investigated. • The cytoprotective role of CYP2A5 in BR hepatotoxicity was determined. • BR

  2. Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

    Science.gov (United States)

    Bouzenna, Hafsia; Hfaiedh, Najla; Bouaziz, Mouhamed; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

    2017-12-01

    Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

  3. Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison

    International Nuclear Information System (INIS)

    Charles, Grantley D.; Gennings, Chris; Tornesi, Belen; Kan, H. Lynn; Zacharewski, Timothy R.; Bhaskar Gollapudi, B.; Carney, Edward W.

    2007-01-01

    In the evaluation of chemical mixture toxicity, it is desirable to develop an evaluation paradigm which incorporates some critical attributes of real world exposures, particularly low dose levels, larger numbers of chemicals, and chemicals from synthetic and natural sources. This study evaluated the impact of low level exposure to a mixture of six synthetic chemicals (SC) under conditions of co-exposure to various levels of plant-derived phytoestrogen (PE) compounds. Estrogenic activity was evaluated using an in vitro human estrogen receptor (ER) transcriptional activation assay and an in vivo immature rat uterotrophic assay. Initially, dose-response curves were characterized for each of the six SCs (methoxyclor, o,p-DDT, octylphenol, bisphenol A, β-hexachlorocyclohexane, 2,3-bis(4-hydroxyphenyl)-propionitrile) in each of the assays. The six SCs were then combined at equipotent ratios and tested at 5-6 dose levels spanning from very low, sub-threshold levels, to a dose in which every chemical in the mixture was at its individual estrogenic response threshold. The SC mixtures also were tested in the absence or presence of 5-6 different levels of PEs, for a total of 36 (in vitro) or 25 (in vivo) treatment groups. Both in vitro and in vivo, low concentrations of the SC mixture failed to increase estrogenic responses relative to those induced by PEs alone. However, significant increases in response occurred when each chemical in the SC mixture was near or above its individual response threshold. In vitro, interactions between high-doses of SCs and PEs were greater than additive, whereas mixtures of SCs in the absence of PEs interacted in a less than additive fashion. In vivo, the SC and PE mixture responses were consistent with additivity. These data illustrate a novel approach for incorporating key attributes of real world exposures in chemical mixture toxicity assessments, and suggest that chemical mixture toxicity is likely to be of concern only when the mixture

  4. The effect of the phytoestrogen genistein on myocardial protection, preconditioning and oxidative stress.

    Science.gov (United States)

    Sbarouni, Eftihia; Iliodromitis, Efstathios K; Zoga, Anastasia; Vlachou, Georgia; Andreadou, Ioanna; Kremastinos, Dimitrios Th

    2006-08-01

    We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase. We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg(-1) day(-1) subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined. We found significant differences between the groups-p protect ischemic myocardium in either ovariectomized or non-ovariectomized animals-BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups. Genistein, at this dose, does not reduce infarct size per se nor abolishes the

  5. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  6. Influence of partial replacement of soya bean meal by faba beans or peas in heavy pigs diet on meat quality, residual anti-nutritional factors and phytoestrogen content.

    Science.gov (United States)

    Gatta, Domenico; Russo, Claudia; Giuliotti, Lorella; Mannari, Claudio; Picciarelli, Piero; Lombardi, Lara; Giovannini, Luca; Ceccarelli, Nello; Mariotti, Lorenzo

    2013-06-01

    The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.

  7. Development of an updated phytoestrogen database for use with the SWAN food frequency questionnaire: intakes and food sources in a community-based, multiethnic cohort study.

    Science.gov (United States)

    Huang, Mei-Hua; Norris, Jean; Han, Weijuan; Block, Torin; Gold, Ellen; Crawford, Sybil; Greendale, Gail A

    2012-01-01

    Phytoestrogens, heterocyclic phenols found in plants, may benefit several health outcomes. However, epidemiologic studies of the health effects of dietary phytoestrogens have yielded mixed results, in part due to challenges inherent in estimating dietary intakes. The goal of this study was to improve the estimates of dietary phytoestrogen consumption using a modified Block Food Frequency Questionnaire (FFQ), a 137-item FFQ created for the Study of Women's Health Across the Nation (SWAN) in 1994. To expand the database of sources from which phytonutrient intakes were computed, we conducted a comprehensive PubMed/Medline search covering January 1994 through September 2008. The expanded database included 4 isoflavones, coumestrol, and 4 lignans. The new database estimated isoflavone content of 105 food items (76.6%) vs. 14 (10.2%) in the 1994 version and computed coumestrol content of 52 food items (38.0%), compared to 1 (0.7%) in the original version. Newly added were lignans; values for 104 FFQ food items (75.9%) were calculated. In addition, we report here the phytonutrient intakes for each racial and language group in the SWAN sample and present major food sources from which the phytonutrients came. This enhanced ascertainment of phytoestrogens will permit improved studies of their health effects.

  8. The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study.

    Science.gov (United States)

    Zaineddin, Aida Karina; Buck, Katharina; Vrieling, Alina; Heinz, Judith; Flesch-Janys, Dieter; Linseisen, Jakob; Chang-Claude, Jenny

    2012-01-01

    Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.

  9. New animal model for the study of postmenopausal coronary and cerebral artery function: the Watanabe heritable hyperlipidemic rabbit fed on a diet avoiding phytoestrogens

    DEFF Research Database (Denmark)

    Dalsgaard, T; Larsen, C R; Mortensen, A

    2002-01-01

    to treatment for 16 weeks with either 17 beta-estradiol or placebo. The chow used was semi-synthetic, thereby avoiding the influence of phytoestrogens. Ring segments of cerebral and coronary arteries were mounted for isometric tension recordings in myographs. The passive and active length-tension relationships...

  10. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    International Nuclear Information System (INIS)

    Jeng, Yow-Jiun; Watson, Cheryl S

    2009-01-01

    Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH 3 /B 6 /F 10 , originally subcloned from GH 3 cells based on its ability to express high levels of the membrane estrogen receptor-α. We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol) were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH 3 /B 6 /F 10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary

  11. Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of mesothelial cells exposed to peritoneal dialysis fluids.

    Science.gov (United States)

    Kratochwill, Klaus; Boehm, Michael; Herzog, Rebecca; Lichtenauer, Anton Michael; Salzer, Elisabeth; Lechner, Michael; Kuster, Lilian; Bergmeister, Konstantin; Rizzi, Andreas; Mayer, Bernd; Aufricht, Christoph

    2012-03-01

    Exposure of mesothelial cells to peritoneal dialysis fluids (PDF) results in cytoprotective cellular stress responses (CSR) that counteract PDF-induced damage. In this study, we tested the hypothesis that the CSR may be inadequate in relevant models of peritoneal dialysis (PD) due to insufficient levels of glutamine, resulting in increased vulnerability against PDF cytotoxicity. We particularly investigated the role of alanyl-glutamine (Ala-Gln) dipeptide on the cytoprotective PDF stress proteome. Adequacy of CSR was investigated in two human in vitro models (immortalized cell line MeT-5A and mesothelial cells derived from peritoneal effluent of uraemic patients) following exposure to heat-sterilized glucose-based PDF (PD4-Dianeal, Baxter) diluted with medium and, in a comparative proteomics approach, at different levels of glutamine ranging from depletion (0 mM) via physiological (0.7 mM) to pharmacological levels (8 mM administered as Ala-Gln). Despite severe cellular injury, expression of cytoprotective proteins was dampened upon PDF exposure at physiological glutamine levels, indicating an inadequate CSR. Depletion of glutamine aggravated cell injury and further reduced the CSR, whereas addition of Ala-Gln at pharmacological level restored an adequate CSR, decreasing cellular damage in both PDF exposure systems. Ala-Gln specifically stimulated chaperoning activity, and cytoprotective processes were markedly enhanced in the PDF stress proteome. Taken together, this study demonstrates an inadequate CSR of mesothelial cells following PDF exposure associated with low and physiological levels of glutamine, indicating a new and potentially relevant pathomechanism. Supplementation of PDF with pharmacological doses of Ala-Gln restored the cytoprotective stress proteome, resulting in improved resistance of mesothelial cells to exposure to PDF. Future work will study the clinical relevance of CSR-mediated cytoprotection.

  12. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

    International Nuclear Information System (INIS)

    Duursen, Majorie B.M. van; Smeets, Evelien E.J.W.; Rijk, Jeroen C.W.; Nijmeijer, Sandra M.; Berg, Martin van den

    2013-01-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast

  13. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Duursen, Majorie B.M. van, E-mail: M.vanDuursen@uu.nl [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands); Smeets, Evelien E.J.W. [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands); Rijk, Jeroen C.W. [RIKILT - Institute for Food Safety, Wageningen UR, P.O. Box 230, 6700 AE, Wageningen (Netherlands); Nijmeijer, Sandra M.; Berg, Martin van den [Endocrine Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, PO Box 80177, 3508 TD, Utrecht (Netherlands)

    2013-06-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast

  14. Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy.

    Science.gov (United States)

    Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

    2017-03-18

    Jatropha ( Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C -glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

  15. Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.)

    Science.gov (United States)

    Castro-Vazquez, Lucia; Alañón, María Elena; Rodríguez-Robledo, Virginia; Pérez-Coello, María Soledad; Hermosín-Gutierrez, Isidro; Díaz-Maroto, María Consuelo; Jordán, Joaquín; Galindo, María Francisca; Arroyo-Jiménez, María del Mar

    2016-01-01

    Grapefruit (Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C) and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C) exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf.) peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies. PMID:26904169

  16. Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas Grown in Southern Italy

    Directory of Open Access Journals (Sweden)

    Teresa Papalia

    2017-03-01

    Full Text Available Jatropha (Jatropha curcas L. is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C-glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

  17. Antiradical and Cytoprotective Activities of Several C-Geranyl-substituted Flavanones from Paulownia tomentosa Fruit

    Directory of Open Access Journals (Sweden)

    Ana Lopes

    2010-08-01

    Full Text Available Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb. Steud. (Scrophulariaceae have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

  18. Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Veronika A. Myasoedova

    2016-08-01

    Full Text Available The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6 were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011 and by 5.2% in placebo recipients (p = 0.020; low density lipoprotein (LDL cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040 and by 5.2% in placebo recipients (non-significant, NS; high density lipoprotein (HDL cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS and by 4.5% in placebo recipients (p = 0.038; triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS and by

  19. Antioxidant and Cytoprotective Effects of Tibetan Tea and Its Phenolic Components

    Directory of Open Access Journals (Sweden)

    Hong Xie

    2018-01-01

    Full Text Available Tibetan tea (Kangzhuan is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea (LATT was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+-catechin, (−-catechin gallate (CG, (−-epicatechin gallate (ECG, and (−-epigallocatechin gallate. Gallic acid, the four catechins, and LATT were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO• scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of ECG were always lower than those of CG. Gallic acid and the four catechins were also suggested to chelate Fe2+ based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC−ESI−Q−TOF−MS/MS analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts. In a flow cytometry assay, (+-catechin and LATT was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H+-transfer, and Fe2+-chelating pathways to exhibit

  20. Antioxidant and Cytoprotective Effects of Tibetan Tea and Its Phenolic Components.

    Science.gov (United States)

    Xie, Hong; Li, Xican; Ren, Zhenxing; Qiu, Weimin; Chen, Jianlan; Jiang, Qian; Chen, Ban; Chen, Dongfeng

    2018-01-24

    Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea ( LATT ) was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+)-catechin, (-)-catechin gallate ( CG ), (-)-epicatechin gallate ( ECG ), and (-)-epigallocatechin gallate). Gallic acid, the four catechins, and LATT were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of ECG were always lower than those of CG . Gallic acid and the four catechins were also suggested to chelate Fe 2+ based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF) products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts). In a flow cytometry assay, (+)-catechin and LATT was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H⁺-transfer, and Fe 2+ -chelating pathways to exhibit antioxidative or

  1. Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes

    NARCIS (Netherlands)

    Donatus, I A; Sardjoko,; Vermeulen, N P

    1990-01-01

    The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to

  2. Genistein, a phytoestrogen, improves total cholesterol, and Synergy, a prebiotic, improves calcium utilization, but there were no synergistic effects.

    Science.gov (United States)

    Legette, LeeCole L; Lee, Wang-Hee; Martin, Berdine R; Story, Jon A; Arabshahi, Ali; Barnes, Stephen; Weaver, Connie M

    2011-08-01

    Prebiotics and phytoestrogens have sparked great interest because evidence indicates that the consumption of these dietary constituents leads to lower cholesterol levels and inhibition of postmenopausal bone loss. The aim of this study was to determine the effect of both a prebiotic (Synergy) and a phytoestrogen (genistein) on bone and blood lipid levels in an animal model of postmenopausal women. A 4-week feeding study was conducted in 5-month-old ovariectomized (OVX) Sprague-Dawley rats to examine the effect of genistein, Synergy (a prebiotic), and genistein and Synergy combined on bone density and strength, calcium metabolism, and lipid biomarkers. There were six treatment groups: sham control, OVX control, OVX rats receiving daily estradiol injections, and OVX rats receiving an AIN-93M diet supplement with 200 ppm genistein, with 5% Synergy or with 200 ppm genistein and 5% Synergy combined. The rats receiving genistein had significantly lower total serum cholesterol concentrations than OVX rats in the control group (17%), OVX rats receiving daily estradiol injections (14%), and OVX rats fed the 5% Synergy diet (19%). Consumption of Synergy improved calcium absorption efficiency (41%) compared with nonconsumption (OVX control). Sham control rats had a significantly higher femoral bone density, as determined by underwater weighing, than did the rats in all of the OVX groups. Genistein consumption restored total and trabecular bone mineral density at the distal femur similar to the levels of sham rats. Genistein supplementation imparts modest heart health benefits and improves bone geometry at the distal femur, and prebiotic consumption (Synergy) results in improved calcium utilization strength in ovariectomized rats, but the combination produced no synergistic effects.

  3. Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria gambir and betel quid with and without calcium hydroxide.

    Science.gov (United States)

    Sazwi, Nordin Nur; Nalina, Thurairajah; Abdul Rahim, Zubaidah Haji

    2013-12-11

    Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and

  4. An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires

    Science.gov (United States)

    Vernekar, Amit A.; Sinha, Devanjan; Srivastava, Shubhi; Paramasivam, Prasath U.; D'Silva, Patrick; Mugesh, Govindasamy

    2014-11-01

    Nanomaterials with enzyme-like properties has attracted significant interest, although limited information is available on their biological activities in cells. Here we show that V2O5 nanowires (Vn) functionally mimic the antioxidant enzyme glutathione peroxidase by using cellular glutathione. Although bulk V2O5 is known to be toxic to the cells, the property is altered when converted into a nanomaterial form. The Vn nanozymes readily internalize into mammalian cells of multiple origin (kidney, neuronal, prostate, cervical) and exhibit robust enzyme-like activity by scavenging the reactive oxygen species when challenged against intrinsic and extrinsic oxidative stress. The Vn nanozymes fully restore the redox balance without perturbing the cellular antioxidant defense, thus providing an important cytoprotection for biomolecules against harmful oxidative damage. Based on our findings, we envision that biocompatible Vn nanowires can provide future therapeutic potential to prevent ageing, cardiac disorders and several neurological conditions, including Parkinson’s and Alzheimer’s disease.

  5. Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Karine Andreau

    2012-01-01

    Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

  6. Yeast as a Tool to Study Signaling Pathways in Mitochondrial Stress Response and Cytoprotection

    Directory of Open Access Journals (Sweden)

    Maša Ždralević

    2012-01-01

    Full Text Available Cell homeostasis results from the balance between cell capability to adapt or succumb to environmental stress. Mitochondria, in addition to supplying cellular energy, are involved in a range of processes deciding about cellular life or death. The crucial role of mitochondria in cell death is well recognized. Mitochondrial dysfunction has been associated with the death process and the onset of numerous diseases. Yet, mitochondrial involvement in cellular adaptation to stress is still largely unexplored. Strong interest exists in pharmacological manipulation of mitochondrial metabolism and signaling. The yeast Saccharomyces cerevisiae has proven a valuable model organism in which several intracellular processes have been characterized in great detail, including the retrograde response to mitochondrial dysfunction and, more recently, programmed cell death. In this paper we review experimental evidences of mitochondrial involvement in cytoprotection and propose yeast as a model system to investigate the role of mitochondria in the cross-talk between prosurvival and prodeath pathways.

  7. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    without submandibular glands. Exogenous EGF and saliva with a high but still physiological concentration of EGF significantly reduced the median area in the stomach displaying ulcers and ulcerations, whereas saliva without EGF had no effect. Although EGF is a known inhibitor of gastric acid secretion......The role of submandibular epidermal growth factor in protection of the gastric mucosa was investigated in rats. Removal of the submandibular glands and thereby submandibular epidermal growth factor (EGF) caused rats to develop gastric lesions (ulcerations and ulcers) after administration......, the dose used in the present study had no effect on gastric acid secretion in chronic gastric fistula rats; removal of the submandibular glands also did not have any such effect. We conclude that exocrine secretion of submandibular EGF has a cytoprotective function in the stomach, an effect that may...

  8. Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

    Science.gov (United States)

    Sedlic, Filip; Muravyeva, Maria Y; Sepac, Ana; Sedlic, Marija; Williams, Anna Marie; Yang, Meiying; Bai, Xiaowen; Bosnjak, Zeljko J

    2017-01-01

    Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017

  9. Cytoprotective effect of glutaraldehyde erythropoietin on HEK293 kidney cells after silver nanoparticle exposure

    Directory of Open Access Journals (Sweden)

    Sooklert K

    2016-02-01

    Full Text Available Kanidta Sooklert,1,2 Supreecha Chattong,3 Krissanapong Manotham,3 Chawikan Boonwong,1 I-yanut Klaharn,1 Depicha Jindatip,4 Amornpun Sereemaspun1,4 1Nanobiomedicine Laboratory, Department of Anatomy, Faculty of Medicine, 2Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, 3Renal Unit, Department of Medicine, Lerdsin General Hospital, 4Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: The toxic effects from exposure to silver nanoparticles (AgNPs, which are broadly present in many consumer products, have long raised concerns. Many studies have focused on the mechanisms of nanosilver, which cause toxicity in human cells, but little is known about prevention of this type of injury. This study investigated the in vitro effects of glutaraldehyde erythropoietin (GEPO, a cytoprotective compound derived from erythropoietin, in terms of cell protection against AgNP-induced injury. HEK293 cells were pretreated with or without GEPO before administration of AgNPs. The protective effects of GEPO in this cell line were assessed by the percentage of viable cells, alterations of cell morphology, and the proliferative capability of the cells. In addition, we assessed the role of GEPO in lowering cellular oxidative stress and regulating expression of the anti-apoptotic protein Bcl2. The results showed rescue effects on the percentage of viable and proliferative cells among GEPO pretreated cells. Pretreatment with GEPO maintained the normal cell shape and ultrastructural morphology. Moreover, GEPO reduced the generation of reactive oxygen species in cells and activated expression of Bcl2, which are the major mechanisms in protection against cellular toxicity induced by AgNPs. In conclusion, our study showed that the cytotoxic effects from exposure to AgNPs can be prevented by GEPO. Keywords: glutaraldehyde erythropoietin, silver nanoparticles, cytoprotection

  10. Antioxidant and cytoprotective properties of D-tagatose in cultured murine hepatocytes.

    Science.gov (United States)

    Paterna, J C; Boess, F; Stäubli, A; Boelsterli, U A

    1998-01-01

    D-Tagatose is a zero-energy producing ketohexose that is a powerful cytoprotective agent against chemically induced cell injury. To further explore the underlying mechanisms of cytoprotection, we investigated the effects of D-tagatose on both the generation of superoxide anion radicals and the consequences of oxidative stress driven by prooxidant compounds in intact cells. Primary cultures of hepatocytes derived from male C57BL/6 mice were exposed to the redox cycling drug nitrofurantoin (NFT). Lethal cell injury induced by 300 microM NFT was completely prevented by high concentrations (20 mM) of D-tagatose, whereas equimolar concentrations of glucose, mannitol, or xylose were ineffective. The extent of NFT-induced intracellular superoxide anion radical formation was not altered by D-tagatose, indicating that the ketohexose did not inhibit the reductive bioactivation of NFT. However, the NFT-induced decline of the intracellular GSH content was largely prevented by D-tagatose. The sugar also afforded complete protection against NFT toxicity in hepatocytes that had been chemically depleted of GSH. Furthermore, the ketohexose fully protected from increases in both membrane lipid peroxidation and protein carbonyl formation. In addition, D-tagatose completely prevented oxidative cell injury inflicted by toxic iron overload with ferric nitrilotriacetate (100 microM). In contrast, D-tagatose did not protect against lethal cell injury induced by tert-butyl hydroperoxide, a prooxidant which acts by hydroxyl radical-independent mechanisms and which is partitioned in the lipid bilayer. These results indicate that D-tagatose, which is a weak iron chelator, can antagonize the iron-dependent toxic consequences of intracellular oxidative stress in hepatocytes. The antioxidant properties of D-tagatose may result from sequestering the redox-active iron, thereby protecting more critical targets from the damaging potential of hydroxyl radical.

  11. PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

    2016-04-01

    Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

  12. Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells.

    Science.gov (United States)

    Chen, Pei-Yi; Ho, Yi-Ru; Wu, Ming-Jiuan; Huang, Shun-Ping; Chen, Po-Kong; Tai, Mi-Hsueh; Ho, Chi-Tang; Yen, Jui-Hung

    2015-01-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), a flavonol compound of flavonoids, exhibits a broad spectrum of biological activities including anti-oxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The aim of this study is to investigate the cytoprotective effect of fisetin and the underlying molecular mechanism against hypoxia-induced cell death in PC12 cells. The results of this study showed that fisetin significantly restored the cell viability of PC12 cells under both cobalt chloride (CoCl₂)- and low oxygen-induced hypoxic conditions. Treatment with fisetin successfully reduced the CoCl₂-mediated reactive oxygen species (ROS) production, which was accompanied by an increase in the cell viability of PC12 cells. Furthermore, we found that treatment of PC12 cells with fisetin markedly upregulated hypoxia-inducible factor 1α (HIF-1α), its nuclear accumulation and the hypoxia-response element (HRE)-driven transcriptional activation. The fisetin-mediated cytoprotection during CoCl₂ exposure was significantly attenuated through the administration of HIF-1α siRNA. Moreover, we demonstrated that MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK and phosphatidylinositol 3-kinase (PI3 K) inhibitors significantly blocked the increase in cell survival that was induced by fisetin treatment under hypoxic conditions. Consistently, increased phosphorylation of ERK, p38 and Akt proteins was observed in PC12 cells treated with fisetin. However, the fisetin-induced HRE-driven transcription was not affected by inhibition of these kinase signaling pathways. Current results reveal for the first time that fisetin promotes cell survival and protects against hypoxia-induced cell death through ROS scavenging and the activation of HIF1α-, MAPK/ERK-, p38 MAPK- and PI3 K/Akt-dependent signaling pathways in PC12 cells.

  13. Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

    Science.gov (United States)

    Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

    2017-10-01

    Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Data set on the characterization of the phytoestrogenic extract and isolated compounds of the roots of Inula racemosa Hook F (Asteraceae

    Directory of Open Access Journals (Sweden)

    Mangathayaru Kalachaveedu

    2018-04-01

    Full Text Available The data presented in this article are related to the research article entitled ‘ Phyto estrogenic effect of Inula racemosa Hook. f – A cardio protective root drug in traditional medicine, (Mangathayaru K, Divya R, Srivani T et al., 2018 [1]. It describes the characterization details of the root extract and the compounds isolated from them that were shown to be phytoestrogenic in vivo and in vitro respectively. Keywords: Alantolactone, Isoalantolactone, Stigmasterol glycoside, Inulin

  15. Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis

    Directory of Open Access Journals (Sweden)

    Li eLi

    2016-05-01

    Full Text Available Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae. The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP dose-dependently (0-1 µg/ml, demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 µg/ml induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the antiestrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 µg/ml inhibited breast cancer cell growth, with a stronger antiproliferative effect than resveratrol, a widely studied analogue of bakuchiol. High doses of bakuchiol (4 µg/ml, 7 µg/ml and 10 µg/ml were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15, Myt1, P-Wee1 (Ser642, p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce

  16. A novel strategy to activate cytoprotective genes in the injured brain

    International Nuclear Information System (INIS)

    Zhao, Jing; Redell, John B.; Moore, Anthony N.; Dash, Pramod K.

    2011-01-01

    Highlights: → A strategy to increase cytoprotective gene expression in injured tissue is outlined. → A peptide containing a DEETGE motif can increase Nrf2 responsive genes in vivo. → Gene expression in injured brains requires a calpain cleavage site. → This peptide decreases BBB compromise when infused pre- or post-brain injury. → Cleavage sites for disease-specific proteases could be used to treat that condition. -- Abstract: The transcription factor nuclear factor E2-related factor 2 (Nrf2) regulates the expression of multiple cytoprotective genes that have been shown to offer protection in response to a number of insults. The present study describes a novel strategy to increase expression of Nrf2-responsive genes in brain injured mice. Under normal conditions, the adapter protein Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and promotes its proteosomal degradation in the cytoplasm. The amino acid sequence DEETGE, located at amino acid 77-82 of Nrf2, is critical for Nrf2-Keap1 interaction, and synthetic peptides containing this sequence can be used to disrupt the complex in vitro. We observed that intracerebroventricular (i.c.v.) infusion of a peptide containing the DEETGE sequence along with the cell transduction domain of the HIV-TAT protein (TAT-DEETGE) into brain-injured mice did not increase the mRNA levels for Nrf2-driven genes. However, when a calpain cleavage sequence was introduced between the TAT sequence and the DEETGE sequence, the new peptide (TAT-CAL-DEETGE) increased the mRNA levels of these genes. Increased gene expression was not observed when the TAT-CAL-DEETGE peptide was injected into uninjured animals. Furthermore, injection of TAT-CAL-DEETGE peptides before or after brain injury reduced blood-brain barrier compromise, a prominent secondary pathology that negatively influences outcome. The present strategy to increase Nrf2-responsive gene expression can be adapted to treat other insults or diseases based on their

  17. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    Science.gov (United States)

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  18. Cytoprotection of Human Endothelial Cells From Menadione Cytotoxicity by Caffeic Acid Phenethyl Ester: The Role of Heme Oxygenase-1

    Science.gov (United States)

    2008-06-08

    cells (HUVEC) to evaluate potential gene expression involvement. CAPE exhibited dose- dependent cytoprotection of HUVEC. A gene screen with...highly induced (8.25-fold) by CAPE compared to DMSO control. To validate this particular microarray screening result, quantitative real-time RT-PCR was...the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. The Journal of Biological Chemistry 279, 8919–8929. Minami, T

  19. Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

    Science.gov (United States)

    Kim, Dong-Hyun; Kim, Baek

    2011-01-01

    The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors. PMID:21765914

  20. Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat.

    Directory of Open Access Journals (Sweden)

    Yuri Kim

    Full Text Available The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors.

  1. Evaluation of the nutraceutical, antioxidant and cytoprotective properties of ripe pistachio (Pistacia vera L., variety Bronte) hulls.

    Science.gov (United States)

    Barreca, Davide; Laganà, Giuseppina; Leuzzi, Ugo; Smeriglio, Antonella; Trombetta, Domenico; Bellocco, Ersilia

    2016-04-01

    Every year tons of pistachio hulls are separated and eliminated, as waste products, from pistachio seeds. In this study the hulls of ripe pistachios were extracted with two organic solvents (ethanol and methanol) and characterized for phenolic composition, antioxidant power and cytoprotective activity. RP-HPLC-DAD-FLU separation enabled us to identify 20 derivatives, including and by far the most abundant gallic acid, 4-hydroxybenzoic acid, protocatechuic acid, naringin, eriodictyol-7-O-glucoside, isorhamnetin-7-O-glucoside, quercetin-3-O-rutinoside, isorhamnetin-3-O-glucoside and catechin. Methanol extraction gave the highest yields for all classes of compounds and presented a higher scavenging activity in all the antioxidant assays performed. The same was found for cytoprotective activity on lymphocytes, lipid peroxidation and protein degradation. These findings highlight the strong antioxidant and cytoprotective activity of the extract components, and illustrate how a waste product can be used as a source of nutraceuticals to employ in manufacturing industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins

    International Nuclear Information System (INIS)

    Nakaso, Kazuhiro; Nakamura, Chiharu; Sato, Hiromi; Imamura, Keiko; Takeshima, Takao; Nakashima, Kenji

    2006-01-01

    Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, γGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD

  3. Cytoprotective effects of atmospheric-pressure plasmas against hypoxia-induced neuronal injuries

    Science.gov (United States)

    Yan, Xu; Meng, Zhaozhong; Ouyang, Jiting; Qiao, Yajun; Li, Jiaxin; Jia, Mei; Yuan, Fang; (Ken Ostrikov, Kostya

    2018-02-01

    Atmospheric pressure plasma jet (APPJ) has recently been the focus of cytoprotective research due to the physiological roles of ROS and RNS. In the current study, we investigated the effect of APPJ treatment on the hypoxia (1% oxygen) induced cell injuries. SH-SY5Y cells were treated by APPJ for different duration and incubated in normoxic condition (20% oxygen) for 5 h followed by 24 h hypoxia treatment. Cell viability was evaluated by lactate dehydrogenase (LDH) release and further monitored using the electric cell-substrate impedance sensing (ECIS) system after APPJ treatment. Results showed that APPJ could reduce cell injuries after 24 h hypoxia, which was consistent with the ECIS results. Furthermore, extracellular NO and H2O2 production was significantly increased with the APPJ treatment. It was also interesting to find that APPJ treatment reduced SH-SY5Y cells proliferation in the hypoxic microenvironment during the first 20 h of hypoxia. Although more work was still need to clarify whether the cell viability maintenance was related to the cell proliferation during hypoxia, our results provide the first evidence of real-time cell viability changes after APPJ treatment under both normoxic and hypoxic conditions, which could provide evidence for the neuroprotective applications of APPJ.

  4. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

    Science.gov (United States)

    Bath, Sundeep

    2015-01-01

    Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

  5. Piper betle Induced Cytoprotective Genes and Proteins via the Nrf2/ARE Pathway in Aging Mice.

    Science.gov (United States)

    Aliahmat, Nor Syahida; Abdul Sani, Nur Fathiah; Wan Hasan, Wan Nuraini; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2016-01-01

    The objective of this study was to elucidate the underlying antioxidant mechanism of aqueous extract of Piper betle (PB) in aging rats. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE pathway involving phase II detoxifying and antioxidant enzymes plays an important role in the antioxidant system by reducing electrophiles and reactive oxygen species through induction of phase II enzymes and proteins. Genes and proteins of phase II detoxifying antioxidant enzymes were analyzed by QuantiGenePlex 2.0 Assay and Western blot analysis. PB significantly induced genes and proteins of phase II and antioxidant enzymes, NAD(P)H quinone oxidoreductase 1, and catalase in aging mice (p < 0.05). The expression of these enzymes were stimulated via translocation of Nrf2 into the nucleus, indicating the involvement of ARE, a cis-acting motif located in the promoter region of nearly all phase II genes. PB was testified for the first time to induce cytoprotective genes through the Nrf2/ARE signaling pathway, thus unraveling the antioxidant mechanism of PB during the aging process. © 2016 S. Karger AG, Basel.

  6. Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

    Science.gov (United States)

    Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

    2008-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

  7. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

    Science.gov (United States)

    Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

    2006-02-15

    We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

  8. Cytoprotective effect of cytoflavinum in the treatment of thermal injuries of various severity levels

    Directory of Open Access Journals (Sweden)

    Alexey J. Bozhedomov

    2012-12-01

    Full Text Available The research aimed to conduct studying of cytoprotective effect of cytoflavinum in thermal traumas of various severity levels. Material and methods – 169 patients were included into the research with thermal burns and with a favorable outcome and the severity of a thermal injury from 30 to 170 points according Frank index. 28 patients received cytoflavinum in a complex therapy in a standard dosage. Results – During the cytoflavinum usage in patients with the severity of a thermal injury more than 60 points by Frank there had been fixed: the decrease of a systemic inflammatory response syndrome (SIRS, reduction of stab neutrophils content, slower decrease of erythrocytes, smaller activation of thrombopoiesis, decrease of concentration of the vascular endothelial growth factor. In the group of patients with thermal injuries less than 60 points who had been receiving cytoflavinum there had not positive effects been fixed. Conclusion – Cytoflavinum is the most effective when the severity of a thermal trauma is more than 60 points by Frank.

  9. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jae Yun [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Seung Sik [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Da Eon [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Bang, Joon Seok [Graduate School of Clinical Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Jung, Young Suk [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  10. Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts

    Directory of Open Access Journals (Sweden)

    Craciunescu Oana

    2012-09-01

    Full Text Available Abstract Background Arnica montana L. and Artemisia absinthium L. (Asteraceae are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study, A. montana and A. absinthium ethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. Results A. absinthium extract showed a higher antioxidant capacity than A. montana extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10–100 mg/L A. montana and 10–500 mg/L A. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/L A. montana and 10–300 mg/L A. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and A. absinthium extracts restored the proportion of cells in each phase of the cell cycle. Conclusions A. montana and A. absinthium extracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use of A. montana and A. absinthium in treatment of skin disorders.

  11. Orthodontic forces induce the cytoprotective enzyme heme oxygenase-1 in rats

    Directory of Open Access Journals (Sweden)

    Christiaan M. Suttorp

    2016-07-01

    Full Text Available Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL, and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalization. Heme oxygenase-1 (HO-1 forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Ni-Ti 10 cN coil spring. The contralateral side served as control. After 6, 12, 72, 96 and 120 hrs rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of multinuclear osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in the mononuclear cell population within the PDL at both the apposition- and resorption side. Shortly after appliance placement HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 hours. Some osteoclasts were HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of cytoprotective enzymes as HO-1 in the PDL determines the level of hyalinization and, subsequently, fast and slow tooth movers during orthodontic treatment.

  12. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    International Nuclear Information System (INIS)

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-01-01

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  13. Cytoprotection mediated antiulcer effect of aqueous fruit pulp extract of Cucumis sativus

    Directory of Open Access Journals (Sweden)

    Swapnil Sharma

    2012-05-01

    Full Text Available Objective: The study was aimed to evaluate the gastroprotective potential of Cucumis Sativus fruit pulp aqueous extract (CSE in gastric ulcerated rats. Methods: Cytoprotective potential was evaluated via oral administration of CSE at the doses of 250, 500 &1000 mg/kg three times in a day, for 5 days before the induction of ulcers in indomethacin and pyloric ligation induced ulcer model. Further, its effects were studied on various parameters volume of gastric juice, pH, free and total acidity, protein concentration, acid output in gastric juice, lipid peroxide (LPO, and activities of enzymic antioxidants-super oxide dismutase (SOD and catalase (CAT in gastric mucosa. The levels of hexose, hexosamine, sialic acid, fucose in gastric mucosa and gastric juice were also examined. The extent of healing was also determined with post administration of CSE at the same doses & dosage schedule in acetic acid induced model. Results: In indomethacin and pyloric ligation model, the pretreatment with CSE and ranitidine significantly reduced the lesion index, in comparison with control treated group (P< 0.05. The percentages of protection of ulcers were 25.8, 65.7, 80.6 & 93.8 for the treated groups of CSE and ranitidine whereas in pyloric ligation it was 31.26, 55.18, 93.26 & 95.51 respectively. In pyloric ligation model, CSE resulted in significant increase in pH, enzymic antioxidants i.e. SOD & CAT, with a significant decrease in volume of gastric juice, free and total acidity, protein & carbohydrate concentration and LPO levels. In acetic acid inducer model, treatment with Cucumis sativus (CSE caused significant reduction in lesion index in when compared to control treated group, providing evidence for ulcer healing capacity of it. The presence of the flavonoids and polyphenols may be responsible for the gastroprotective effect of CSE. Conclusions: The aqueous fruit pulp extract of Cucumis sativus (CSE has a gastroprotective property.

  14. Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism.

    Science.gov (United States)

    Alva, Norma; Alva, Ronald; Carbonell, Teresa

    2016-01-01

    In clinical and experimental settings, a great deal of effort is being made to protect cells and tissues against harmful conditions and to facilitate metabolic recovery following these insults. Much of the recent attention has focused on the protective role of a natural form of sugar, fructose 1,6-bisphosphate (F16bP). F16bP is a high-energy glycolytic intermediate that has been shown to exert a protective action in different cell types and tissues (including the brain, kidney, intestine, liver and heart) against various harmful conditions. For example, there is much evidence that it prevents neuronal damage due to hypoxia and ischemia. Furthermore, the cytoprotective effects of F16bP have been documented in lesions caused by chemicals or cold storage, in a decrease in mortality during sepsis shock and even in the prevention of bone loss in experimental osteoporosis. Intriguingly, protection in such a variety of targets and animal models suggests that the mechanisms induced by F16bP are complex and involve different pathways. In this review we will discuss the most recent theories concerning the molecular model of action of F16bP inside cells. These include its incorporation as an energy substrate, the mechanism for the improvement of ATP availability, and for preservation of organelle membrane stability and functionality. In addition we will present new evidences regarding the capacity of F16bP to decrease oxidative stress by limiting free radical production and improving antioxidant systems, including the role of nitric oxide in the protective mechanism induced by F16bP. Finally we will review the proposed mechanisms for explaining its anti-inflammatory, immunomodulatory and neuroprotective properties.

  15. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chandan Kanta Das

    2018-03-01

    Full Text Available Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC, and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6 of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549rDOX20 and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468r5-FU2000 cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549rDOX20 and MDA-MB-468r5-FU2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer.

  16. Occupational Styrene Exposure Induces Stress-Responsive Genes Involved in Cytoprotective and Cytotoxic Activities

    Science.gov (United States)

    Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

    2013-01-01

    Objective The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Methods Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Results Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. Conclusion The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure. PMID:24086524

  17. An Odyssey of cytoprotective bisbenzimidazole as therapeutic agent for human well being

    International Nuclear Information System (INIS)

    Tandon, Vibha

    2014-01-01

    Radiotherapy is utilized by 80% patients as a part of their treatment to most prevalent disease like cancer. Ionizing radiation causes radiolysis of water, generation of ROS and has deleterious effect penetrating the living tissues resulting in the-transfer of radiation energy to the biological materials. Radioprotectors protect the normal cells from the unwanted radiation damage. Since the beginning of the nuclear era, despite extensive research on the development of radioprotectors from natural and synthetic compounds, success has been limited. The only clinically acceptable radioprotector, amifostine, has inherent dose-limiting toxicities and has therefore stimulated extensive search for nontoxic, effective, and alternative radioprotectors. We have developed a cytoprotective radioprotector DMA, having a bisbenzimidazole nucleus. Relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of NFkB inducing kinase (NIK) as one of the plausible target. Subsequently, over expression and knock down of NIK suggested that DMA affects NFkB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation. We observed 51% radioprotection in untreated cells that attenuated to 17% in siRNA NIK treated U87 cells at 24h. Further studies concluded that the Coactivation of AKT/NFkB triggered by DMA, is a reason behind protection against ionizing radiation-induced apoptosis of normal cells, and this was consistent with the alteration of DNA-PKcs. Pharmacokinetic (PK) evaluations and bioavailability measurements proved superior in vivo efficacy, higher AUCs, greater residence time of DMA. (author)

  18. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

    International Nuclear Information System (INIS)

    Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung

    2006-01-01

    Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4 + T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4 + T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1

  19. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    International Nuclear Information System (INIS)

    Seppen, Jurgen

    2012-01-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  20. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Seppen, Jurgen, E-mail: j.seppen@amc.uva.nl

    2012-11-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  1. Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

    DEFF Research Database (Denmark)

    Huelsenbeck, Stefanie C; Roggenkamp, Dennis; May, Martin

    2013-01-01

    B expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1...... without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1....

  2. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells.

    Science.gov (United States)

    Das, Chandan Kanta; Linder, Benedikt; Bonn, Florian; Rothweiler, Florian; Dikic, Ivan; Michaelis, Martin; Cinatl, Jindrich; Mandal, Mahitosh; Kögel, Donat

    2018-03-01

    Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549 r DOX 20 ) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468 r 5-FU 2000 ) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549 r DOX 20 and MDA-MB-468 r 5-FU 2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Effects of Trifolium alexandrinum phytoestrogens on oestrous behaviour, ovarian activity and reproductive performance of ewes during the non-breeding season.

    Science.gov (United States)

    Hashem, N M; El-Azrak, K M; Nour El-Din, A N M; Sallam, S M; Taha, T A; Salem, M H

    2018-03-08

    Phytoestrogens are classified as naturally occurring endocrine disrupting chemicals that may affect reproductive performance of farm animals. To investigate the effects of Berseem clover phytoestrogens on reproductive performance of seasonal anoestrus ewes, twenty four late pregnant Rahmani ewes were fed either Berseem clover or maize silage (n = 12/treatment). Treatment started 2 months prepartum and continued until oestrous induction (week 8 postpartum), using the CIDR-eCG based protocol, and early pregnancy. Throughout the 2-8 weeks postpartum, oestrous rate and ovarian activity were not affected by treatment. After oestrous induction, ewes in both groups expressed comparable oestrous rates; however feeding Berseem clover extended (P ewes fed maize silage than for those fed Berseem clover. Fecundity and litter size tended to be greater (about 35%; P = 0.132 and 0.085, respectively) in the maize silage fed ewes. In conclusion, feeding Berseem clover throughout seasonal anoestrus disrupted aspects of behavioural oestrus and there was less luteal P 4 synthesis and fecundity of ewes. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Chemical sporulation and germination: cytoprotective nanocoating of individual mammalian cells with a degradable tannic acid-FeIII complex

    Science.gov (United States)

    Lee, Juno; Cho, Hyeoncheol; Choi, Jinsu; Kim, Doyeon; Hong, Daewha; Park, Ji Hun; Yang, Sung Ho; Choi, Insung S.

    2015-11-01

    Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature.Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature. Electronic supplementary information (ESI) available: Experimental details, LSCM images, and SEM and TEM images. See DOI: 10.1039/c5nr05573c

  5. Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

    Directory of Open Access Journals (Sweden)

    Kumiko Tamaki

    2012-01-01

    Full Text Available Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43, a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6. Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

  6. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells

    Directory of Open Access Journals (Sweden)

    Felipe Ávila

    2017-01-01

    Full Text Available The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs from Chilean raspberries (Rubus geoides, strawberries (Fragaria chiloensis ssp. chiloensis f. chiloensis, and currants (Ribes magellanicum and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis. This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food.

  7. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells.

    Science.gov (United States)

    Ávila, Felipe; Theoduloz, Cristina; López-Alarcón, Camilo; Dorta, Eva; Schmeda-Hirschmann, Guillermo

    2017-01-01

    The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM) and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs) from Chilean raspberries ( Rubus geoides ), strawberries ( Fragaria chiloensis ssp. chiloensis f . chiloensis ), and currants ( Ribes magellanicum ) and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML) and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis . This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food.

  8. Erythrocytes and cell line-based assays to evaluate the cytoprotective activity of antioxidant components obtained from natural sources.

    Science.gov (United States)

    Botta, Albert; Martínez, Verónica; Mitjans, Montserrat; Balboa, Elena; Conde, Enma; Vinardell, M Pilar

    2014-02-01

    Oxidative stress can damage cellular components including DNA, proteins or lipids, and may cause several skin diseases. To protect from this damage and addressing consumer's appeal to natural products, antioxidants obtained from algal and vegetal extracts are being proposed as antioxidants to be incorporated into formulations. Thus, the development of reliable, quick and economic in vitro methods to study the cytoactivity of these products is a meaningful requirement. A combination of erythrocyte and cell line-based assays was performed on two extracts from Sargassum muticum, one from Ulva lactuca, and one from Castanea sativa. Antioxidant properties were assessed in erythrocytes by the TBARS and AAPH assays, and cytotoxicity and antioxidant cytoprotection were assessed in HaCaT and 3T3 cells by the MTT assay. The extracts showed no antioxidant activity on the TBARS assay, whereas their antioxidant capacity in the AAPH assay was demonstrated. On the cytotoxicity assays, extracts showed low toxicity, with IC50 values higher than 200μg/mL. C. sativa extract showed the most favourable antioxidant properties on the antioxidant cytoprotection assays; while S. muticum and U. lactuca extracts showed a slight antioxidant activity. This battery of methods was useful to characterise the biological antioxidant properties of these natural extracts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

    Science.gov (United States)

    Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

    2007-03-01

    The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

  10. Cytoprotective and Antioxidant Effects of an Edible Herb, Enhydra fluctuans Lour. (Asteraceae), against Experimentally Induced Lead Acetate Intoxication.

    Science.gov (United States)

    Dua, Tarun K; Dewanjee, Saikat; Khanra, Ritu; Joardar, Swarnalata; Barma, Sujata; Das, Shilpa; Zia-Ul-Haq, M; De Feo, Vincenzo

    2016-01-01

    Enhydra fluctuans Lour. (Asteraceae), an edible aquatic herb, is traditionally employed against toxic effects of heavy metals in India. The present study was planned to discover the protective effect of edible extract of E. fluctuans (AEEF) against Pb toxicity. The cytoprotective role of AEEF was determined on murine hepatocytes employing MTT assay and Hoechst staining. The effects on lipid peroxidation, protein carbonylation, endogenous redox systems and the transcription levels of apoptotic proteins were studied after incubating the hepatocytes with AEEF (400 μg/ml) + Pb-acetate (6.8 μM). The defensive role of AEEF (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication was measured in mice by in vivo assays. Biochemical, haematological and histological parameters, intracellular Pb burden and redox status were measured. AEEF exhibited a concentration dependent cytoprotective effect against Pb-induced cytotoxicity in vitro. Pb-acetate incubation significantly (p intoxicated animals. However, concurrent administration of AEEF (100 mg/kg) could significantly (p < 0.05-0.01) reinstate the Pb-acetate mediated toxicity. Presence of metal chelators and phyto-antioxidants within AEEF would offer overall protection through promoting Pb clearance coupled with restoring redox balance.

  11. Phytoestrogens/insoluble fibers and colonic estrogen receptor β: Randomized, double-blind, placebo-controlled study

    Science.gov (United States)

    Principi, Mariabeatrice; Di Leo, Alfredo; Pricci, Maria; Scavo, Maria Principia; Guido, Raffaella; Tanzi, Sabina; Piscitelli, Domenico; Pisani, Antonio; Ierardi, Enzo; Comelli, Maria Cristina; Barone, Michele

    2013-01-01

    AIM: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study. PMID:23885143

  12. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    International Nuclear Information System (INIS)

    Chen, Zhi-Dong; Xu, Liang; Tang, Kan-Kai; Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong; Sun, Ren-Hua; Mo, Shi-Jing

    2016-01-01

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  13. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi-Dong [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Xu, Liang [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Tang, Kan-Kai [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Sun, Ren-Hua, E-mail: jqin168@hotmail.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Mo, Shi-Jing, E-mail: msj860307@163.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China)

    2016-09-10

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  14. Role of the p-Coumaroyl Moiety in the Antioxidant and Cytoprotective Effects of Flavonoid Glycosides: Comparison of Astragalin and Tiliroside

    Directory of Open Access Journals (Sweden)

    Xican Li

    2017-07-01

    Full Text Available The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•+ scavenging, •O2– scavenging, and Fe2+-chelating assays. The results of these assays revealed that astragalin and tiliroside both exhibited dose-dependent activities; however, tiliroside exhibited lower IC50 values than astragalin. In the Fe2+-chelating assay, tiliroside gave a larger shoulder-peak at 510 nm than astragalin, and was also found to be darker in color. Both of these compounds were subsequently evaluated in a Fenton-induced mesenchymal stem cell (MSC damaged assay, where tiliroside performed more effectively as a cytoprotective agent than astragalin. Tiliroside bearing a 6′′-O-p-coumaroyl moiety exhibits higher antioxidant and cytoprotective effects than astragalin. The 6′′-O-p-coumaroyl moiety of tiliroside not only enhances the possibility of electron-transfer and hydrogen-atom-transfer-based multi-pathways, but also enhances the likelihood of Fe-chelating. The p-coumaroylation of the 6"-OH position could therefore be regarded as a potential approach for improving the antioxidant and cytoprotective effects of flavonoid glycosides in MSC implantation therapy.

  15. Effect of acetylation on antioxidant and cytoprotective activity of polysaccharides isolated from pumpkin (Cucurbita pepo, lady godiva).

    Science.gov (United States)

    Song, Yi; Yang, Yang; Zhang, Yuyu; Duan, Liusheng; Zhou, Chunli; Ni, Yuanying; Liao, Xiaojun; Li, Quanhong; Hu, Xiaosong

    2013-10-15

    Acetylation of pumpkin (Cucurbita pepo, lady godiva variety) polysaccharide using acetic anhydride with pyridines as catalyst under different conditions was conducted to obtain different degrees of acetylation on a laboratory scale. Furthermore, antioxidant activities and cytoprotective effects of pumpkin polysaccharide and its acetylated derivatives were investigated employing various established in vitro systems. Results showed that addition of pyridine as catalyst could increase the degree of substitution, whereas volume of acetic anhydride had little effect. The acetylated polysaccharides in DPPH scavenging radical activity assay, superoxide anion radical activity assay and reducing power assay exhibited higher antioxidant activity than that of unmodified polysaccharide. H2O2-induced oxidative damages on rat thymic lymphocyte were also prevented by pumpkin polysaccharide and its acetylated derivatives and the derivatives presented higher protective effects. On the whole, acetylated polysaccharide showed relevant antioxidant activity both in vitro and in a cell system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Irradiation Effect on the antioxidant properties, anti-microbial and cytoprotective of the bark of Punica granatum

    International Nuclear Information System (INIS)

    Sanaa, Chahnez

    2013-01-01

    The bark of pomegranate has been used for some years to treat various health problems . Several studies have focused on specifying these problems, including antibacterial , antioxidant and cytoprotective . The use of pomegranate rind powder is an effective treatment against gastric ulcer and intestines and to strengthen the wall of the gastrointestinal tract. In this work, we studied the effects of gamma irradiation on the type antibacterial, anti-ulcer and bark grenade. This study was conducted on powdered pomegranate bark irradiated by applying decreasing radiation doses from 25kGy to 1.25KGy. All of our results shows that irradiation with a low degree improves the effectiveness of pomegranate bark for the treatment of gastric ulcer , however high degree irradiation enhances the antibacterial activity of bark pomegranate against Staphylococcus aureus.

  17. Antioxidative and cytoprotective effects of andrographolide against CCl4-induced hepatotoxicity in HepG2 cells.

    Science.gov (United States)

    Krithika, R; Verma, R J; Shrivastav, P S

    2013-05-01

    This article describes antioxidative and cytoprotective property of andrographolide, a major active component of the plant Andrographis paniculata (A. paniculata). High yields (2.7%) of andrographolide was isolated from the aerial parts of this plant via silica column chromatography. The purity of the compound was determined by high-performance thin-layer chromatography (HPTLC) and reversed phase high-performance liquid chromatography (HPLC) analysis. The structure was elucidated using techniques such as UV-visible spectrophotometry, elemental analysis, Fourier transform infrared (FT-IR), (1)H nuclear magnetic resonance ((1)H NMR), (13)C nuclear magnetic resonance ((13)C NMR) and mass spectral analysis and the data obtained were comparable with reported results. It was observed that andrographolide exhibited significant antioxidative property (IC50 = 3.2 µg/ml) by its ability to scavenge a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) as compared to known antioxidants like ascorbic acid, butylated hydroxy toluene (BHT) and the plant extract. The cytoprotective role of andrographolide against carbon tetrachloride (CCl4) toxicity in human hepatoma HepG2 cell line was assessed using trypan blue exclusion test, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, by estimation of various leakage enzymes and by measuring the glutathione levels. The recovery obtained for andrographolide treatment in the presence of CCl4 was two-fold compared to A. paniculata extract for all other related biochemical parameters investigated. The results of the study indicate that andrographolide is a potent inhibitor of CCl4-mediated lipid peroxidation.

  18. A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells.

    Science.gov (United States)

    Wang, Qian; Guo, Yalan; Jiang, Shanshan; Dong, Mengxue; Kuerban, Kudelaidi; Li, Jiyang; Feng, Meiqing; Chen, Ying; Ye, Li

    2018-01-15

    Lung adenocarcinoma is the most primary histologic subtype of non-small cell lung cancer (NSCLC). Compound 8b, a novel coumarin derivative with phenylsulfonylfuroxan group, shows significant antiproliferation activity against lung adenocarcinoma cell with low toxicity. This study aims to uncover the potential of compound 8b in relation to apoptosis as well as autophagy induction in lung adenocarcinoma cells. The cytotoxicity and apoptosis of A549 and H1299 cells induced by compound 8b were detected by MTT, microscope and western blot analysis. Autophagy was determined by TEM, confocal microscopy and western blot analysis. Akt/mTOR and Erk signaling pathway were also examined by western blot analysis. First, significant growth inhibition and caspase-dependent apoptosis were observed in compound 8b-treated A549 and H1299 cells. Then, we confirmed compound 8b-induced autophagy by autophagosomes formation, upregulated expression of autophagy-related protein LC3-II and autophagic flux. Importantly, abolishing autophagy using inhibitors and ATG5 siRNA enhanced the cytotoxicity of compound 8b, indicating the cytoprotective role of autophagy in lung adenocarcinoma. Further mechanistic investigations suggested that Akt/mTOR and Erk signaling pathways contributed to autophagy induction by compound 8b. This results demonstrate that compound 8b induces caspase-dependent apoptosis as well as cytoprotective autophagy in lung adenocarcinoma cells, which may provide scientific evidence for developing this furoxan-based NO-releasing coumarin derivative as a potential anti-lung adenocarcinoma therapeutic agents. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-02-01

    Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

  20. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.

    Science.gov (United States)

    Berlanga-Acosta, Jorge; Abreu-Cruz, Angel; Herrera, Diana García-Del Barco; Mendoza-Marí, Yssel; Rodríguez-Ulloa, Arielis; García-Ojalvo, Ariana; Falcón-Cama, Viviana; Hernández-Bernal, Francisco; Beichen, Qu; Guillén-Nieto, Gerardo

    2017-01-01

    Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs' binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of "drugable" peptides awaits for a definitive clinical niche.

  1. Molecular analysis of the genus Asparagus based on matK sequences and its application to identify A. racemosus, a medicinally phytoestrogenic species.

    Science.gov (United States)

    Boonsom, Teerawat; Waranuch, Neti; Ingkaninan, Kornkanok; Denduangboripant, Jessada; Sukrong, Suchada

    2012-07-01

    The plant Asparagus racemosus is one of the most widely used sources of phytoestrogens because of its high content of the steroidal saponins, shatavarins I-IV, in roots. The dry root of A. racemosus, known as "Rak-Sam-Sip" in Thai, is one of the most popular herbal medicines, used as an anti-inflammatory, an aphrodisiac and a galactagogue. Recently, the interest in plant-derived estrogens has increased tremendously, making A. racemosus particularly important and a possible target for fraudulent labeling. However, the identification of A. racemosus is generally difficult due to its similar morphology to other Asparagus spp. Thus, accurate authentication of A. racemosus is essential. In this study, 1557-bp nucleotide sequences of the maturase K (matK) gene of eight Asparagus taxa were analyzed. A phylogenetic relationship based on the matK gene was also constructed. Ten polymorphic sites of nucleotide substitutions were found within the matK sequences. A. racemosus showed different nucleotide substitutions to the other species. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the matK gene was developed to discriminate A. racemosus from others. Only the 650-bp PCR product from A. racemosus could be digested with BssKI into two fragments of 397 and 253-bp while the products of other species remained undigested. Ten commercially crude drugs were analyzed and revealed that eight samples were derived from A. racemosus while two samples of that were not. Thus, the PCR-RFLP analysis of matK gene was shown to be an effective method for authentication of the medicinally phytoestrogenic species, A. racemosus. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. LC-MS analysis and cytoprotective effect against the mercurium and aluminium toxicity by bioactive products of Psidium brownianum Mart. ex DC.

    Science.gov (United States)

    Sobral-Souza, Celestina E; Silva, Ana R P; Leite, Nadghia F; Costa, José G M; Menezes, Irwin R A; Cunha, Francisco A B; Rolim, Larissa A; Coutinho, Henrique D M

    2018-03-21

    This study aimed to verify the chelating, antioxidant and cytoprotective activities of Psidium brownianum Mart. Ex DC against mercury and aluminum. The ethanolic extract, as well as the tannic and flavonoid fractions, were prepared and subjected to liquid chromatography-mass spectrometry analysis. Ferric ion reduction and antioxidant activity measurement using the FRAP method were performed with P. brownianum. After determining the sub-allelopathic doses, germination tests using Lactuca sativa (lettuce) seeds were performed. The main compounds identified in the extract and fractions were: quercetin and its derivatives; myricetin and its derivatives; gallic acid; ellagic acid; quinic acid and gallocatechin. The Minimum Inhibitory Concentration (MIC) for all samples were ≥ 1024 μg/mL. The flavonoid fraction in association with mercury chloride demonstrated cytoprotection (p flavonoids. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Modulation of transglutaminase 2 activity in H9c2 cells by PKC and PKA signalling: a role for transglutaminase 2 in cytoprotection

    Science.gov (United States)

    Almami, Ibtesam; Dickenson, John M; Hargreaves, Alan J; Bonner, Philip L R

    2014-01-01

    BACKGROUND AND PURPOSE Tissue transglutaminase (TG2) has been shown to mediate cell survival in many cell types. In this study, we investigated whether the role of TG2 in cytoprotection was mediated by the activation of PKA and PKC in cardiomyocyte-like H9c2 cells. EXPERIMENTAL APPROACH H9c2 cells were extracted following stimulation with phorbol-12-myristate-13-acetate (PMA) and forskolin. Transglutaminase activity was determined using an amine incorporating and a protein crosslinking assay. The presence of TG isoforms (TG1, 2, 3) was determined using Western blot analysis. The role of TG2 in PMA- and forskolin-induced cytoprotection was investigated by monitoring H2O2-induced oxidative stress in H9c2 cells. KEY RESULTS Western blotting showed TG2 >> TG1 protein expression but no detectable TG3. The amine incorporating activity of TG2 in H9c2 cells increased in a time and concentration-dependent manner following stimulation with PMA and forskolin. PMA and forskolin-induced TG2 activity was blocked by PKC (Ro 31-8220) and PKA (KT 5720 and Rp-8-Cl-cAMPS) inhibitors respectively. The PMA- and forskolin-induced increases in TG2 activity were attenuated by the TG2 inhibitors Z-DON and R283. Immunocytochemistry revealed TG2-mediated biotin-X-cadaverine incorporation into proteins and proteomic analysis identified known (β-tubulin) and novel (α-actinin) protein substrates for TG2. Pretreatment with PMA and forskolin reversed H2O2-induced decrease in MTT reduction and release of LDH. TG2 inhibitors R283 and Z-DON blocked PMA- and forskolin-induced cytoprotection. CONCLUSIONS AND IMPLICATIONS TG2 activity was stimulated via PKA- and PKC-dependent signalling pathways in H9c2 cells These results suggest a role for TG2 in cytoprotection induced by these kinases. PMID:24821315

  4. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    International Nuclear Information System (INIS)

    Gonzalez-Rubio, Sandra; Linares, Clara I.; Bello, Rosario I.; Gonzalez, Raul; Ferrin, Gustavo; Hidalgo, Ana B.; Munoz-Gomariz, Elisa; Rodriguez, Blanca A.; Barrera, Pilar; Ranchal, Isidora; Duran-Prado, Mario; Aguilar-Melero, Patricia; De la Mata, Manuel; Muntane, Jordi

    2010-01-01

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca 2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca 2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca 2+ entrance was induced by A23187 in HepG2. Cell death, Ca 2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca 2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca 2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca 2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca 2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca 2+ -dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  5. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Rubio, Sandra; Linares, Clara I; Bello, Rosario I [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Gonzalez, Raul; Ferrin, Gustavo [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREH o Ciberehd) (Spain); Hidalgo, Ana B [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Munoz-Gomariz, Elisa [Department of Biostatistics, Reina Sofia University Hospital, Cordoba (Spain); Rodriguez, Blanca A [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Barrera, Pilar; Ranchal, Isidora [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREH o Ciberehd) (Spain); Duran-Prado, Mario [Instituto de Parasitologia y Biomedicina Lopez Neyra, CSIC, Granada (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion CB06/03, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (Spain); Aguilar-Melero, Patricia [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); De la Mata, Manuel [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREH o Ciberehd) (Spain); Muntane, Jordi [Liver Research Unit, Reina Sofia University Hospital, Cordoba (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREH o Ciberehd) (Spain)

    2010-01-15

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca{sup 2+} on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca{sup 2+} pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca{sup 2+} entrance was induced by A23187 in HepG2. Cell death, Ca{sup 2+} mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca{sup 2+} concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca{sup 2+} entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca{sup 2+} entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca{sup 2+} concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca{sup 2+}-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  6. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    International Nuclear Information System (INIS)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi; Kotani, Eiji; Hirano, Tomoko; Nakajima, Yumiko; Matsumoto, Goichi; Mori, Hajime

    2014-01-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals

  7. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Energy Technology Data Exchange (ETDEWEB)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Kotani, Eiji [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan); Hirano, Tomoko [Venture Laboratory, Kyoto Institute of Technology, Kyoto (Japan); Nakajima, Yumiko [Functional Genomics Group, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Matsumoto, Goichi [Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, Yokohama (Japan); Mori, Hajime, E-mail: hmori@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan)

    2014-09-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals.

  8. Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage

    Science.gov (United States)

    Takeda, Taka-aki; Mu, Anfeng; Tai, Tran Tien; Kitajima, Sakihito; Taketani, Shigeru

    2015-01-01

    It is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain, and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage. PMID:25990790

  9. Isolating a cytoprotective compound from Ganoderma tsugae: effects on induction of Nrf-2-related genes in endothelial cells.

    Science.gov (United States)

    Wei, Yu-Shan; Wung, Being-Sun; Lin, Yuan-Chun; Hsieh, Chia-Wen

    2009-08-01

    Ganoderma tsugae is a medicinal fungus with several biological activities. It has long been used as a folk remedy for the promotion of health and longevity in China and other oriental countries. Here, a bioactive fraction of G. tsugae was progressively purified to be enriched in the activity of cytoprotective enzymes. The highest bioactivity was detected in the 20% EtOH-precipitated fraction, which was prepared from submerged fermentation filtrate of G. tsugae. Following further purification by gel filtration chromatography and acetone extraction, the most bioactive fraction, F5-2, was identified as a peptidoglycan-like compound. Extracts of G. tsugae (F5-2) induced heme oxygenase-1 (HO-1) and thioredoxin reductase-1 (TrxR1) expression in endothelial cells by increasing NF-E2-related factor-2 (Nrf2) nuclear translocation. Pretreatment with F5-2 increased intracellular glutathione (GSH) and protected against H(2)O(2), suggesting that induction of these antioxidant enzymes is important in protection against oxidative stress. Hence the bioactive peptidoglycan-like compound from G. tsugae might protect endothelial cells.

  10. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    Science.gov (United States)

    Clafshenkel, William P; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Koepsel, Richard R; Russell, Alan J

    2016-01-01

    Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  11. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    William P Clafshenkel

    Full Text Available Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP, may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidylsuberate (BS3. A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  12. Chemical study, antioxidant, anti-hypertensive, and cytotoxic/cytoprotective activities of Centaurea cyanus L. petals aqueous extract.

    Science.gov (United States)

    Escher, Graziela Bragueto; Santos, Jânio Sousa; Rosso, Neiva Deliberali; Marques, Mariza Boscacci; Azevedo, Luciana; do Carmo, Mariana Araújo Vieira; Daguer, Heitor; Molognoni, Luciano; Prado-Silva, Leonardo do; Sant'Ana, Anderson Souza; da Silva, Marcia Cristina; Granato, Daniel

    2018-05-19

    This study aimed to optimise the experimental conditions of extraction of the phytochemical compounds and functional properties of Centaurea cyanus petals. The following parameters were determined: the chemical composition (LC-ESI-MS/MS), the effects of pH on the stability and antioxidant activity of anthocyanins, the inhibition of lipid peroxidation, antioxidant activity, anti-hemolytic activity, antimicrobial, anti-hypertensive, and cytotoxic/cytoprotective effect, and the measurements of intracellular reactive oxygen species. Results showed that the temperature and time influenced (p ≤ 0.05) the content of flavonoids, anthocyanins, and FRAP. Only the temperature influenced the total phenolic content, non-anthocyanin flavonoids, and antioxidant activity (DPPH). The statistical approach made it possible to obtain the optimised experimental extraction conditions to increase the level of bioactive compounds. Chlorogenic, caffeic, ferulic, and p-coumaric acids, isoquercitrin, and coumarin were identified as the major compounds in the optimised extract. The optimised extract presented anti-hemolytic and anti-hypertensive activity in vitro, in addition to showing stability and reversibility of anthocyanins and antioxidant activity with pH variation. The C. cyanus extract exhibited high IC 50 and GI 50 (>900 μg/mL) values for all cell lines, meaning low cytotoxicity. Based on the stress oxidative assay, the extract exhibited pro-oxidant action (10-100 μg/mL) but did not cause damage or cell death. Copyright © 2018. Published by Elsevier Ltd.

  13. In vitro antioxidant and cytoprotective properties of Maillard reaction products from phloridzin-amino acid model systems.

    Science.gov (United States)

    Han, Linna; Li, Feng; Yu, Qijian; Li, Dapeng

    2018-01-01

    The aim of this study was to investigate in vitro antioxidant activities and cytoprotective effect of Maillard reaction products (MRPs) from phloridzin (Pz)-amino acid model systems. Their structures were also characterised by Fourier transform-infrared spectroscopy (FTIR). MRPs were prepared from the Pz-methionine (Met), Pz-lysine (Lys), Pz-isoleucine (Ile), Pz-histidine (His) or Pz-glutamic acid (Glu) model system. The Pz-Lys MRPs, rich in antioxidant potency, were subjected to ultrafiltration to yield four MRPs fractions with different molecular weights (Mw). The fraction with Mw 30-50 kDa had significantly (P Maillard reaction. The results obtained in this study may provide some basis for the purported health-promoting effects of MRPs and their potential application as antioxidant agents in food industry. Also, it is important for our understanding of the variation of bioactive substances in food during thermal processing. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. The Effect of Soybean-Derived Phytoestrogens on Concentrations of Plasma Isoflavones, 15-keto-13,14-dihydroprostaglandin F2α and Progesterone in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Jarmila Watzková

    2010-01-01

    Full Text Available The objective of the study was to determine the effect of soybean-derived phytoestrogens and their metabolites on the activity of sex hormones during the oestrous cycle in multiparous lactating dairy cows. The experiment was carried out on 4 multiparous lactating Holstein cows in the form of replicated Latin square in double reversal design. The experiment in the total length of 168 days was divided into 4 periods of 42 days, each consisting of a 21-day preliminary period and a 21-day collecting period. Cows were divided into 2 groups of 2 cows. The control group (C was fed a diet based on extruded rapeseed cake while the experimental group (S was fed a diet containing extruded full-fat soya. The intake of total isoflavones was 3297 mg/d in S and 58.0 mg/d in C (P P P > 0.05. Plasma concentration of prostaglandine PGFM throughout the oestrous cycle in the experimental group (S tended to be higher (P = 0.095 than in the control group (C. No differences in the length of the oestrous cycle between the cows fed different diets were observed.

  15. MODULATION OF THE INFLAMMATORY CYTOKINES AND CYTOPROTECTIVE ENZYME BY BILIRUBIN TREATMENT TO ENHANCE CUTANEOUS WOUND HEALING IN RATS

    Directory of Open Access Journals (Sweden)

    Raju Prasad

    2017-06-01

    Full Text Available Inflammation is the main process of wound healing where expression of certain cytokines likes Interleukin-10 (IL-10 and Tumour necrosis factor ∝ (TNF ∝ plays an important role. In view of the antioxidant potential of bilirubin, the present study was aimed to evaluate time-dependent (day 3, 7, 14 wound healing effects of bilirubin ointment (0.3% in excisional wound model in rats. Thirty-six acclimatized healthy male Wistar rats (120-150g were divided into control and treated groups containing 18 rats each. Each group was further sub- divided into three sub-groups (day 3, 7 and 14 days, n= 6. The ointment base (soft paraffin 90%, lanolin 5% and hard paraffin 5% and bilirubin ointment (0.3% were applied topically once daily for 14 days in control and treated group respectively. The wound area was determined on days 3, 7, and 14. The mRNA expression of TNF ∝ gene and IL-10 gene were determined on days 3, 7 and 14 by Real Time PCR and their protein levels by ELISA method. The protein expression of cyto-protective enzyme HO-1 (Heme oxygenage-1 and growth factor VEGF (Vascular growth factor was determined by western blotting method. The mRNA expression and protein level of TNF ∝ was significantly reduced and IL-10 was significantly increased whereas the expression of HO-1 enzyme and VEGF was significantly increased in treated group on days 3, 7 and 14. It may be concluded that the bilirubin has pro-healing potential.

  16. I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S-enantiomer of rasagiline.

    Directory of Open Access Journals (Sweden)

    Yaron D Barac

    Full Text Available TVP1022, the S-enantiomer of rasagiline (Azilect® (N-propargyl-1R-aminoindan, exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I(1 & I(2 are potential targets for TVP1022 (IC(50 =9.5E-08 M and IC(50 =1.4E-07 M, respectively. Western blotting analysis showed that TVP1022 (1-20 µM dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM. This effect of TVP1022 was significantly attenuated by efaroxan, a selective I(1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I(1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I(1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

  17. I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S-enantiomer of rasagiline.

    Science.gov (United States)

    Barac, Yaron D; Bar-Am, Orit; Liani, Esti; Amit, Tamar; Frolov, Luba; Ovcharenko, Elena; Angel, Itzchak; Youdim, Moussa B H; Binah, Ofer

    2012-01-01

    TVP1022, the S-enantiomer of rasagiline (Azilect®) (N-propargyl-1R-aminoindan), exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I(1) & I(2)) are potential targets for TVP1022 (IC(50) =9.5E-08 M and IC(50) =1.4E-07 M, respectively). Western blotting analysis showed that TVP1022 (1-20 µM) dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was significantly attenuated by efaroxan, a selective I(1) imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I(1)imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I(1)imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

  18. Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin.

    Science.gov (United States)

    Reisman, Scott A; Lee, Chun-Yue I; Meyer, Colin J; Proksch, Joel W; Ward, Keith W

    2014-07-01

    RTA 408 is a member of the synthetic oleanane triterpenoid class of compounds known to potently activate the cytoprotective transcription factor Nrf2. Because skin is constantly exposed to external oxidative stress, such as that from ultraviolet radiation, from chemical exposure, during improper wound healing, and throughout the course of cancer radiation therapy, it may benefit from activation of Nrf2. This study was conducted to evaluate the transdermal penetration properties and Nrf2 activation potential of RTA 408 in normal rat skin. RTA 408 (0.1, 1.0, or 3.0%) was applied topically to the shaved skin of male Sprague-Dawley rats twice daily for 4 days and once on Day 5. Topical application of RTA 408 resulted in transdermal penetration, with low but dose-dependent plasma exposure with AUC(0-24 h) values of 3.6, 26.0, and 41.1 h ng/mL for the 0.1, 1.0, and 3.0% doses, respectively. Further, topical application of RTA 408 resulted in increased translocation of Nrf2 to the nucleus, dose-dependent mRNA induction of Nrf2 target genes (e.g. Nqo1, Srxn1, Gclc, and Gclm), and induction of the protein expression of the prototypical Nrf2 target gene Nqo1 and increased total glutathione (GSH) in normal rat skin. Immunohistochemistry demonstrated that increased staining for Nqo1 and total GSH of structures in both the epidermis and dermis was consistent with the full transdermal penetration of RTA 408. Finally, topically administered RTA 408 was well tolerated with no adverse in-life observations and normal skin histology. Thus, the data support the further development of RTA 408 for the potential treatment of skin diseases.

  19. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  20. Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis.

    Science.gov (United States)

    De Franceschi, Lucia; Bertoldi, Mariarita; De Falco, Luigia; Santos Franco, Sara; Ronzoni, Luisa; Turrini, Franco; Colancecco, Alessandra; Camaschella, Clara; Cappellini, Maria Domenica; Iolascon, Achille

    2011-11-01

    β-thalassemic syndromes are inherited red cell disorders characterized by severe ineffective erythropoiesis and increased levels of reactive oxygen species whose contribution to β-thalassemic anemia is only partially understood. We studied erythroid precursors from normal and β-thalassemic peripheral CD34(+) cells in two-phase liquid culture by proteomic, reverse transcriptase polymerase chain reaction and immunoblot analyses. We measured intracellular reactive oxygen species, heme levels and the activity of δ-aminolevulinate-synthase-2. We exposed normal cells and K562 cells with silenced peroxiredoxin-2 to H(2)O(2) and generated a recombinant peroxiredoxin-2 for kinetic measurements in the presence of H(2)O(2) or hemin. In β-thalassemia the increased production of reactive oxygen species was associated with down-regulation of heme oxygenase-1 and biliverdin reductase and up-regulation of peroxiredoxin-2. In agreement with these observations in β-thalassemic cells we found decreased heme levels related to significantly reduced activity of the first enzyme of the heme pathway, δ-aminolevulinate synthase-2 without differences in its expression. We demonstrated that the activity of recombinant δ-aminolevulinate synthase-2 is inhibited by both reactive oxygen species and hemin as a protective mechanism in β-thalassemic cells. We then addressed the question of the protective role of peroxiredoxin-2 in erythropoiesis by exposing normal cells to oxidative stress and silencing peroxiredoxin-2 in human erythroleukemia K562 cells. We found that peroxiredoxin-2 expression is up-regulated in response to oxidative stress and required for K562 cells to survive oxidative stress. We then showed that peroxiredoxin-2 binds heme in erythroid precursors with high affinity, suggesting a possible multifunctional cytoprotective role of peroxiredoxin-2 in β-thalassemia. In β-thalassemic erythroid cells the reduction of δ-aminolevulinate synthase-2 activity and the increased

  1. The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity.

    Science.gov (United States)

    Mazzio, Elizabeth; Soliman, Karam F A

    2003-01-01

    1-Methyl-4-phenylpyridinium (MPP+) is a mitochondrial Complex I inhibitor and is frequently used to investigate the pathological degeneration of neurons associated with Parkinson's disease (PD). In vitro, extracellular concentration of glucose is one of the most critical factors in establishing the vulnerability of neurons to MPP+ toxicity. While glucose is the primary energy fuel for the brain, central nervous system (CNS) neurons can also take up and utilize other metabolic intermediates for energy. In this study, we compared various monosaccharides, disaccharides, nutritive/non-nutritive sugar alcohols, glycolytic and gluconeogenic metabolic intermediates for their cytoprotection against MPP+ in murine brain neuroblastoma cells. Several monosaccharides were effective against MMP+ (500 microM) including glucose, fructose and mannose, which restored cell viability to 109 +/- 5%, 70 +/- 5%, 99 +/- 3% of live controls, respectively. Slight protective effects were observed in the presence of 3-phosphoglyceric acid and glucose-6-phosphate; however, no protective effects were exhibited by galactose, sucrose, sorbitol, mannitol, glycerol or various gluconeogenic and ketogenic amino acids. On the other hand, fructose 1,6 bisphosphate and gluconeogenic energy intermediates [pyruvic acid, malic acid and phospho(enol)pyruvate (PEP)] were neuroprotective against MPP+. The gluconeogenic intermediates elevated intracellular levels of ATP and reduced propidium iodide (PI) nucleic acid staining to live controls, but did not alter the MPP(+)-induced loss of mitochondrial O2 consumption. These data indicate that malic acid, pyruvic acid and PEP contribute to anaerobic substrate level phosphorylation. The use of hydrazine sulfate to impede gluconeogenesis through PEP carboxykinase (PEPCK) inhibition heightened the protective effects of energy substrates possibly due to attenuated ATP demands from pyruvate carboxylase (PC) activity and pyruvate mitochondrial transport. It was

  2. Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage)

    International Nuclear Information System (INIS)

    Kim, Sang Chan; Byun, Sung Hui; Yang, Chae Ha; Kim, Chul Young; Kim, Jin Woong; Kim, Sang Geon

    2004-01-01

    Glycyrrhizae radix has been popularly used as one of the oldest and most frequently employed botanicals in herbal medicine in Asian countries, and currently occupies an important place in food products. Cadmium (Cd) induces both apoptotic and non-apoptotic cell death, in which alterations in cellular sulfhydryls participate. In the present study, we determined the effects of G. radix extract (GRE) and its representative active components on cell death induced by Cd and explored the mechanistic basis of cytoprotective effects of G. radix. Incubation of H4IIE cells with GRE inhibited cell death induced by 10 μM Cd. Also, GRE effectively blocked Cd (1 μM)-induced cell death potentiated by buthionine sulfoximine (BSO) without restoration of cellular GSH. GRE prevented both apoptotic and non-apoptotic cell injury induced by Cd (10 μM) or Cd (0.3-1 μM) + BSO. Inhibition of Cd-induced cell injury by pretreatment of cells with GRE suggested that the cytoprotective effect result from alterations in the levels of the protein(s) responsible for cell viability. GRE inhibited mitochondrial Bad translocation by Cd or Cd+BSO, and caused restoration of mitochondrial Bcl xL and cytochrome c levels. Cd-induced poly(ADP-ribose)polymerase cleavage in control cells or in cells deprived of sulfhydryls was prevented by GRE treatment. Among the major components present in GRE, liquiritigenin, but not liquiritin, isoliquiritigenin or glycyrrhizin, exerted cytoprotective effect. These results demonstrated that GRE blocked Cd-induced cell death by inhibiting the apoptotic processes involving translocation of Bad into mitochondria, decreases in mitochondrial Bcl xL and cytochrome c, and poly(ADP-ribose)polymerase cleavage

  3. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

  4. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

    International Nuclear Information System (INIS)

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Kanunfre, Carla Cristine; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

    2016-01-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

  5. A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui; Reddy, Shridhivya A.; Lee, Stephanie S-H.; Yang, Hong; Tan, Sock-Hoon [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Hayes, John D. [Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland (United Kingdom); Chui, Wai-Keung [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Chew, Eng-Hui, E-mail: phaceh@nus.edu.sg [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore)

    2013-11-01

    Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E{sub 2} (PGE{sub 2}) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. - Highlights:

  6. Red wine consumption may affect sperm biology: the effects of different concentrations of the phytoestrogen myricetin on human male gamete function.

    Science.gov (United States)

    Aquila, Saveria; Santoro, Marta; De Amicis, Francesca; Guido, Carmela; Bonofiglio, Daniela; Lanzino, Marilena; Cesario, Maria Grazia; Perrotta, Ida; Sisci, Diego; Morelli, Catia

    2013-02-01

    Myricetin is a natural flavonoid, particularly enriched in red wines, whose occurrence is widespread among plants. Despite extensive research, the beneficial effects of Myricetin on human health are still controversial. Here, we tested the estrogen-like effect of the phytoestrogen Myricetin on human ejaculated sperm biology. To this aim, human normozoospermic samples were exposed to increasing concentrations (10 nM, 100 nM, and 1 µM) of Myricetin. Motility, viability, capacitation-associated biochemical changes (i.e., cholesterol efflux and tyrosine phosphorylation), acrosin activity, as well as glucose utilization and fatty-acid oxidation (i.e., glucose and lipid metabolism) were all significantly increased by low doses of Myricetin. Importantly, both estrogen receptors α and β (ERs) and phosphatidylinositol-3-OH kinase (PI3K)/AKT signaling are activated in the presence of Myricetin since these were both abrogated by specific inhibitors of each pathway. Our results show how Myricetin, through ERs and PI3K/AKT signalings, potentiates sperm function. This effect is dose-dependent at low concentrations of Myricetin (up to 100 nM), whereas higher amounts do not seem to improve any further sperm motility, viability, or other tested features, and, in some cases, they reduced or even abrogated the efficacy exerted by lower doses. Further studies are needed to elucidate if high levels of Myricetin, which could be attained even with moderate wine consumption, could synergize with endogenous estrogens in the female reproductive tract, interfering with the physiological sperm fertilization process. Copyright © 2012 Wiley Periodicals, Inc.

  7. The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression.

    Science.gov (United States)

    Maxwell, Thressi; Chun, So-Young; Lee, Kyu-Shik; Kim, Soyoung; Nam, Kyung-Soo

    2017-02-01

    Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In spite of the health benefits of phytoestrogens reducing the risk of osteoporosis, heart disease, and menopausal symptoms, its benefits against the risk of breast cancer have not been fully elucidated. Thus, we investigated the effects of arctigenin on metastasis of breast cancer using both estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cell lines to see if the effects are dependent on the status of ER expression. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. The activity of crucial metastatic protease matrix metalloprotease (MMP)-9 in gelatin zymography was also efficiently decreased by arctigenin, as well as its mRNA expression. Notably, arctigenin exhibited similar anti-metastatic effects even in ER-negative MDA-MB-231 cells, suggesting that the anti-metastatic effects of arctigenin were not exerted via the ER. The upstream signaling pathways involved in the regulation of MMP-9 and urokinase plasminogen activator (uPA) were analyzed using western blotting. The activation of Akt, NF-κB and MAPK (ERK 1/2 and JNK 1/2) was found to be inhibited. Taken together, these data suggest that arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Therefore, we propose that the intake of arctigenin could be an effective supplement for breast cancer patients.

  8. Effects of phytoestrogen supplementation in the feed on the shell gland of laying hens at the end of the laying period.

    Science.gov (United States)

    Wistedt, A; Ridderstråle, Y; Wall, H; Holm, L

    2012-08-01

    Shell quality decreases as laying hens age and the aim of present study was to investigate how a supplement of daidzein, a natural phytoestrogen in soya, affects key factors in the shell gland and eggshell quality in late-stage laying hens. Hybrids of Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB), received either a daidzein diet (50 mg/kg feed) or a control diet from 60 to 72 weeks of age. Both the total number of capillaries and capillaries with carbonic anhydrase (CA) activity were higher in the LSL hybrid than in the LB. After daidzein supplementation the number of CA positive capillaries was unaffected in the LSL but increased in the LB hybrid indicating a higher sensitivity to daidzein in this hybrid. Estrogen receptor alpha and beta (ERα, ERβ) were localized and the complete picture of the two ERs can now be described in shell gland of domestic hens. Nuclear and cytoplasmic staining was generally stronger for ERβ, while membrane associated staining was present only for ERα. Interestingly, capillary endothelium contained only ERβ and since estrogen regulation of CA is well documented, the presence of an endothelial ER provides one possible route for the increase in CA positive capillaries found in LB hybrids. Eggshell quality or egg production was not affected by daidzein supplementation. The hybrids used in this study showed anatomical differences and reacted differently to daidzein supplementation, but if this can be explained by the divergences in ERβ localization noted between the hybrids remains to be clarified. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Kaempferol, a phytoestrogen, suppressed triclosan-induced epithelial-mesenchymal transition and metastatic-related behaviors of MCF-7 breast cancer cells.

    Science.gov (United States)

    Lee, Geum-A; Choi, Kyung-Chul; Hwang, Kyung-A

    2017-01-01

    As a phytoestrogen, kaempferol is known to play a chemopreventive role inhibiting carcinogenesis and cancer progression. In this study, the influences of triclosan, an anti-bacterial agent recently known for an endocrine disrupting chemical (EDC), and kaempferol on breast cancer progression were examined by measuring their effects on epithelial-mesenchymal transition (EMT) and metastatic-related behaviors of MCF-7 breast cancer cells. Morphological changes of MCF-7 cells were observed, and a wound-healing assay was performed after the treatment of triclosan and kaempferol. The effects of triclosan and kaempferol on protein expression of EMT-related markers such as E-cadherin, N-cadherin, Snail, and Slug and metastasis-related markers such as cathepsin B, D, MMP-2 and -9 were investigated by Western blot assay. In microscopic observations, triclosan (10 -6 M) or E2 (10 -9 M) induced transition to mesenchymal phenotype of MCF-7 cells compared with the control. Co-treatment of ICI 182,780 (10 -8 M), an ER antagonist, or kaempferol (25μM) with E2 or triclosan restored the cellular morphology to an epithelial phenotype. In a wound-healing scratch and a transwell migration assay, triclosan enhanced migration and invasion of MCF-7 cells, but co-treatment of kaempferol or ICI 182,780 reduced the migration and invasion ability of MCF-7 cells to the control level. In addition, kaempferol effectively suppressed E2 or triclosan-induced protein expressions of EMT and metastasis promoting markers. Taken together, triclosan may be a distinct xenoestrogenic EDC to promote EMT, migration, and invasion of MCF-7 breast cancer cells through ER. On the other hand, kaempferol can be an alternative chemopreventive agent to effectively suppress the metastatic behavior of breast cancer induced by an endogenous estrogen as well as exogenous xenoestrogenic compounds including triclosan. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Cytotoxicity and Hsp 70 induction in Hep G2 cells in response to zearalenone and cytoprotection by sub-lethal heat shock

    International Nuclear Information System (INIS)

    Hassen, Wafa; Golli, Emna El; Baudrimont, Isabelle; Mobio, A. Theophile; Ladjimi, M. Moncef; Creppy, E. Edmond; Bacha, Hassen

    2005-01-01

    Zearalenone (ZEN) is a mycotoxin with several adverse effects in laboratory and domestic animals. The mechanism of ZEN toxicity that involves mainly binding to oestrogen receptors and inhibition of macromolecules synthesis is not fully understood. Using human hepatocytes Hep G2 cells as a model, the aim of this work was (i) to investigate the ability of ZEN to induce heat shock proteins Hsp 70 and (ii) to find out the mechanisms of ZEN cytotoxicity by examining cell proliferation and protein synthesis. Our study demonstrated that ZEN induces Hsp 70 expression in a time and dose-dependant manner; this induction occurs at non-cytotoxic concentrations, it could be therefore considered as a biomarker of toxicity. A cytoprotective effect of Hsp 70 was elicited when Hep G2 cells were exposed to Sub-Lethal heat shock prior to ZEN treatment and evidenced by a reduced ZEN cytolethality. This cytoprotection suggests that Hsp 70 may constitute an important cellular defence mechanism. Finally, our data show that ZEN is cytotoxic in Hep G2 cells by inhibiting cell proliferation and total protein synthesis and pointed out oxidative damage as possible pathway involved in ZEN toxicity; however, other investigations are needed to further confirm Zen induced oxidative stress

  11. Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Akitoshi Matsuda

    2015-01-01

    Full Text Available Activated protein C (APC has cytoprotective effects on liver ischemia-reperfusion injury (IRI. However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI. Methods. Mice fed either normal diets (ND mice or high fat diets (HF mice, were treated with APC or saline (control and were performed 60 min partial IRI. Moreover, primary steatotic hepatocytes were either untreated or treated with APC and then incubated with H2O2. Results. APC significantly reduced serum transaminase levels and the inflammatory cells infiltration compared with control at 4 h in ND mice and at 24 h in HF mice. APC inhibited sinusoidal endothelial injury in ND mice, but not in HF mice. In contrast, APC activated adenosine monophosphate-activated protein kinase (AMPK phosphorylation in HF mice, but not in ND mice. In the in vitro study, APC significantly increased AMPK phosphorylation, ATP concentration, and survival rates of hepatocytes compared with control. Conclusion. During IRI in normal liver, APC attenuated initial damage by inhibiting inflammatory cell infiltration and sinusoidal endothelial injury, but not in steatotic liver. However, in steatotic liver, APC might attenuate late damage via activation of AMPK.

  12. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway.

    Science.gov (United States)

    Varshney, Ritu; Gupta, Sumeet; Roy, Partha

    2017-06-15

    Lipotoxicity of pancreatic β-cells is the pathological manifestation of obesity-linked type II diabetes. We intended to determine the cytoprotective effect of kaempferol on pancreatic β-cells undergoing apoptosis in palmitic acid (PA)-stressed condition. The data showed that kaempferol treatment increased cell viability and anti-apoptotic activity in PA-stressed RIN-5F cells and murine pancreatic islets. Furthermore, kaempferol's ability to instigate autophagy was illustrated by MDC-LysoTracker red staining and TEM analysis which corroborated well with the observed increase in LC3 puncta and LC3-II protein expressions along with the concomitant decline in p62 expression. Apart from this, the data showed that kaempferol up/down-regulates AMPK/mTOR phosphorylation respectively. Subsequently, upon inhibition of AMPK phosphorylation by AMPK inhibitors, kaempferol-mediated autophagy was abolished which further led to the decline in β-cell survival. Such observations collectively lead to the conclusion that, kaempferol exerts its cytoprotective role against lipotoxicity by activation of autophagy via AMPK/mTOR pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. An exceptionally potent inducer of cytoprotective enzymes: elucidation of the structural features that determine inducer potency and reactivity with Keap1.

    Science.gov (United States)

    Dinkova-Kostova, Albena T; Talalay, Paul; Sharkey, John; Zhang, Ying; Holtzclaw, W David; Wang, Xiu Jun; David, Emilie; Schiavoni, Katherine H; Finlayson, Stewart; Mierke, Dale F; Honda, Tadashi

    2010-10-29

    The Keap1/Nrf2/ARE pathway controls a network of cytoprotective genes that defend against the damaging effects of oxidative and electrophilic stress, and inflammation. Induction of this pathway is a highly effective strategy in combating the risk of cancer and chronic degenerative diseases, including atherosclerosis and neurodegeneration. An acetylenic tricyclic bis(cyano enone) bearing two highly electrophilic Michael acceptors is an extremely potent inducer in cells and in vivo. We demonstrate spectroscopically that both cyano enone functions of the tricyclic molecule react with cysteine residues of Keap1 and activate transcription of cytoprotective genes. Novel monocyclic cyano enones, representing fragments of rings A and C of the tricyclic compound, reveal that the contribution to inducer potency of the ring C Michael acceptor is much greater than that of ring A, and that potency is further enhanced by spatial proximity of an acetylenic function. Critically, the simultaneous presence of two cyano enone functions in rings A and C within a rigid three-ring system results in exceptionally high inducer potency. Detailed understanding of the structural elements that contribute to the reactivity with the protein sensor Keap1 and to high potency of induction is essential for the development of specific and selective lead compounds as clinically relevant chemoprotective agents.

  14. Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

    Science.gov (United States)

    Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

    2008-03-01

    Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

  15. Cytoprotection of human endothelial cells against oxidative stress by 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im): application of systems biology to understand the mechanism of action.

    Science.gov (United States)

    Wang, Xinyu; Bynum, James A; Stavchansky, Solomon; Bowman, Phillip D

    2014-07-05

    Cellular damage from oxidative stress, in particular following ischemic injury, occurs during heart attack, stroke, or traumatic injury, and is potentially reducible with appropriate drug treatment. We previously reported that caffeic acid phenethyl ester (CAPE), a plant-derived polyphenolic compound, protected human umbilical vein endothelial cells (HUVEC) from menadione-induced oxidative stress and that this cytoprotective effect was correlated with the capacity to induce heme oxygenase-1 (HMOX1) and its protein product, a phase II cytoprotective enzyme. To further improve this cytoprotective effect, we studied a synthetic triterpenoid, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), which is known as a potent phase II enzyme inducer with antitumor and anti-inflammatory activities, and compared it to CAPE. CDDO-Im at 200nM provided more protection to HUVEC against oxidative stress than 20μM CAPE. We explored the mechanism of CDDO-Im cytoprotection with gene expression profiling and pathway analysis and compared to that of CAPE. In addition to potent up-regulation of HMOX1, heat shock proteins (HSP) were also found to be highly induced by CDDO-Im in HUVEC. Pathway analysis results showed that transcription factor Nrf2-mediated oxidative stress response was among the top canonical pathways commonly activated by both CDDO-Im and CAPE. Compared to CAPE, CDDO-Im up-regulated more HSP and some of them to a much higher extent. In addition, CDDO-Im treatment affected Nrf2 pathway more significantly. These findings may provide an explanation why CDDO-Im is a more potent cytoprotectant than CAPE against oxidative stress in HUVEC. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Activity of ethanolic extracts leaves of Machaerium floribundum against acne-inducing bacteria, and their cytoprotective and antioxidant effects on fibroblast

    Directory of Open Access Journals (Sweden)

    Lorena Díaz

    2011-08-01

    Full Text Available Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus have been recognized as the bacteria that are involved in the inflammatory process of acne, while oxidants and antioxidants are involved in the repair of cutaneous tissue affected. In this study an evaluation was made of the antibacterial effect by the agar diffusion and broth dilution method, the cytoprotective and antioxidant effect on 3T3 dermic fibroblast cells, treated with hydrogen peroxide and the scavenging capacity of free radicals was determined by the 2, 2-diphenyl-l-picrylhydrazyl (DPPH method as well as the Reducing Power of the ethanolic extracts of the leaves of the Machaerium floribundum. Minimal bactericidal concentrations (MBC were obtained against Propionibacterium acnes and Staphylococcus aureus of 5 mg/mL and 2 mg/mL, respectively. A cytoprotective effect of 111% was observed over the cellular viability of the fibroblasts at 10 μg/mL and an antioxidant effect of 92% over the viability of the fibroblasts treated with hydrogen peroxide at 25 μg/mL. A stimulation of 24% growth of fibroblasts at 50 μg/mL was evidenced. On the other hand a 93% scavenging activity of the DPPH free radical was shown for 100 μg/mL with a CI50 of 34 μg/mL. The reducing power was evidenced to be dependent on the concentration. The results obtained indicated that the ethanolic extract of Machaerium floribundum shows a good antibacterial activity against bacteria that induce acne and a high potential for scavenging of free radicals at relatively low concentrations.

  17. In vitro cytoprotective effects of acetylsalicylic acid, carprofen, meloxicam, or robenacoxib against apoptosis induced by sodium nitroprusside in canine cruciate ligament cells.

    Science.gov (United States)

    Waldherr, Katrin; Zurbriggen, Andreas; Spreng, David E; Forterre, Simone

    2012-11-01

    To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP). Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles. Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E(2) concentrations were measured via an ELISA. Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE(2) production from SNP-damaged cells. Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.

  18. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kume, Toshiaki; Izumi, Yasuhiko [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Park, Si-Bum [Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Hirata, Takashi [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Rehabilitation, Shijonawategakuen University, 5-11-10, Hojo, Daitou-shi, Osaka 574-0011 (Japan); Sugawara, Tatsuya, E-mail: sugawara@kais.kyoto-u.ac.jp [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan)

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  19. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    International Nuclear Information System (INIS)

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-01-01

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin

  20. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    International Nuclear Information System (INIS)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-01-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  1. Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2–ARE pathway

    Science.gov (United States)

    Wang, Rui; Paul, Valerie J.; Luesch, Hendrik

    2013-01-01

    Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE–luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate–cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched

  2. Potential antioxidant and cytoprotective effects of essential oil extracted from Cymbopogon citratus on OxLDL and H2O2 LDL induced Human Peripheral Blood Mononuclear Cells (PBMC

    Directory of Open Access Journals (Sweden)

    Jamuna S.

    2017-06-01

    Full Text Available Cymbopogon citratus (lemon grass is commonly used in traditional folk medicine. The essential oil extracted from C. citratus has been reported as a potential anti-oxidant and anti-inflammatory agent. This study has been designed to explore the protective effect of C. citratus (lemon grass against modified LDL (OxLDL and H2O2 LDL induced cytotoxicity in Peripheral Blood Mononuclear Cells (PBMC. The essential oil extracted from C. citratus (EOC was subjected to FT-IR spectroscopic analysis for the identification of functional groups. In vitro antioxidant assays were carried out to assess the electron donating capability of EOC as compared with a known standard L-ascorbic acid. The cytoprotective effects of EOC were determined in PBMC induced with modified LDL. Spectra obtained from FT-IR analysis showed the presence of functional groups in EOC such as H-bonded, OH stretching, NH stretching, aldehydeCH stretching, aldehyde/ketoneCO stretching, CC-stretching, CH3 bending, CH in plane bending. EOC has greater antioxidant property when compared with the standard L-ascorbic acid. EOC at all test concentrations demonstrated free radical scavenging activity and cytoprotective effect when challenged against modified LDL in PBMC. The above results show EOC as a promising antioxidant and cytoprotective agent.

  3. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    International Nuclear Information System (INIS)

    Li, Kuiqing; Chen, Xu; Liu, Cheng; Gu, Peng; Li, Zhuohang; Wu, Shaoxu; Xu, Kewei; Lin, Tianxin; Huang, Jian

    2015-01-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway

  4. Comparative analysis of the role of small G proteins in cell migration and cell death: Cytoprotective and promigratory effects of RalA

    International Nuclear Information System (INIS)

    Jeon, Hyejin; Zheng, Long Tai; Lee, Shinrye; Lee, Won-Ha; Park, Nammi; Park, Jae-Yong; Heo, Won Do; Lee, Myung-Shik; Suk, Kyoungho

    2011-01-01

    Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with inflammation, tumorigenesis, and metastasis. Our results show that small G proteins of the six families differentially regulate cell death and cell cycle distribution. In particular, our results indicate that Rho family of small G proteins is antiapoptotic. Ras, Rho, and Ran families promoted cell migration. There was no significant correlation between the cell death- and cell migration-regulating activities of the small G proteins. Nevertheless, RalA was not only cytoprotective against multiple chemotherapeutic drugs, but also promigratory inducing stress fiber formation, which was accompanied by the activation of Akt and Erk pathways. Our study provides a framework for further systematic investigation of small G proteins in the perspectives of cell death/survival and motility in inflammation and cancer.

  5. Study on interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part III. In vitro study on the adsorption of selected prokinetic drugs on sucralfate.

    Science.gov (United States)

    Grimling, Bozena; Pluta, Janusz

    2005-01-01

    Adsorbance of certain prokinetic drugs, regulating the motility of the digestive tract, on a cytoprotective drug--sucralfate was investigated. The evaluation of adsorbance capability was carried out by means of a statistical method in in vitro conditions, taking into account environmental pH, concentration of the investigated drugs as well as the form of sucralfate. Obtained results prove that the analyzed active agents are adsorbed on sucralfate at all the investigated pH ranges and the capability of sucralfate binding depends on its form and environmental pH. The highest binding capability was revealed by samples with pH = 3.6 in the presence of sucralfate in the form of suspension, while the lowest binding capability was observed at pH = 1.5 in the presence of sucralfate in the form of paste. The adsorbance capacity of sucralfate (k) at pH = 3.6 is the highest for cisaprid (k = 8.5) and it is significantly lower for metoclopramide (k = 1.5)

  6. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress.

    Science.gov (United States)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. Copyright © 2016. Published by Elsevier Inc.

  7. Mechanisms of CDDO-imidazolide-mediated cytoprotection against acrolein-induced neurocytotoxicity in SH-SY5Y cells and primary human astrocytes.

    Science.gov (United States)

    Speen, Adam; Jones, Colton; Patel, Ruby; Shah, Halley; Nallasamy, Palanisamy; Brooke, Elizabeth A S; Zhu, Hong; Li, Y Robert; Jia, Zhenquan

    2015-10-01

    Acrolein is a ubiquitous unsaturated aldehyde has been implicated in the pathogenesis of various neurological disorders. However, limited study has been conducted into potential therapeutic protection and underlying mechanism against acrolein-induced cytotoxicity via upregulation of cellular aldehyde-detoxification defenses. In this study we have utilized RA-differentiated human SH-SY5Y cells and primary human astrocytes to investigate the induction of glutathione (GSH) by the synthetic triterpenoid 2-cyano-3,12-dixooleana-1,9-dien-28-imidazolide (CDDO-Im) and the protective effects CDDO-Im-mediated antioxidant defenses on acrolein toxicity. Acrolein exposure to RA-differentiated SH-SY5Y cells resulted in a significant time dependent depletion of cellular GSH preceding a reduction in cell viability and LDH release. Further, we demonstrated the predominance of cellular GSH in protection against acrolein-induced cytotoxicity. Buthionine sulfoximine (BSO) at 25μM dramatically depleted GSH and significantly potentiated acrolein-induced cytotoxicity. Pretreatment of the cells with 100nM CDDO-Im afforded a dramatic protection against acrolein-induced cytotoxicity. Pretreatment of BSO and CDDO was found to prevent the CDDO-Im-mediated GSH induction and partially reversed the cytoprotective effects of CDDO-Im against acrolein cytotoxicity. Overall, this study represents for the first time the CDDO-Im mediated upregulation of GSH is a predominant mechanism against acrolein-induced neurotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

    Science.gov (United States)

    Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

    2015-07-14

    Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kuiqing; Chen, Xu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Liu, Cheng [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Gu, Peng; Li, Zhuohang; Wu, Shaoxu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Xu, Kewei [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Lin, Tianxin, E-mail: tianxinl@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Huang, Jian, E-mail: urolhj@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China)

    2015-05-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.

  10. Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

    Science.gov (United States)

    Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

    2018-04-20

    Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

  11. The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema.

    Science.gov (United States)

    Tan, Li Hui; Bahmed, Karim; Lin, Chih-Ru; Marchetti, Nathaniel; Bolla, Sudhir; Criner, Gerard J; Kelsen, Steven; Madesh, Muniswamy; Kosmider, Beata

    2018-02-23

    Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.

  12. Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2-ARE pathway.

    Science.gov (United States)

    Wang, Rui; Paul, Valerie J; Luesch, Hendrik

    2013-04-01

    Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE-luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate-cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with

  13. Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced Enteropathy

    Directory of Open Access Journals (Sweden)

    Yulia Sklyarova

    2017-10-01

    Full Text Available Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs, antitumor drugs and angiotensin-converting enzyme (ACE inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg; methotrexate, an antitumor drug (10 mg/kg; and enalapril, an ACE inhibitor (2 mg/kg/day. 2-[(4-chlorophenyl-carbamoyl-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl-acrylic acid (2C3DHTA was introduced based on the background of medication-induced enteropathy (10 mg/kg/day. The survey showed that malondialdehyde (MDA concentration, myeloperoxidase (MPO activity, superoxide dismutase (SOD, catalase, and NO-synthases (NOS were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI system.

  14. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    C.A. De Souza

    2000-07-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  15. Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Kazuaki Kajimoto

    2014-01-01

    Full Text Available The fatty acid binding protein 4 (FABP4, one of the most abundant proteins in adipocytes, has been reported to have a proinflammatory function in macrophages. However, the physiological role of FABP4, which is constitutively expressed in adipocytes, has not been fully elucidated. Previously, we demonstrated that FABP4 was involved in the regulation of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF production in 3T3-L1 adipocytes. In this study, we examined the effects of FABP4 silencing on the oxidative and endoplasmic reticulum (ER stress in 3T3-L1 adipocytes. We found that the cellular reactive oxygen species (ROS and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH, superoxide dismutase (SOD and glutathione S-transferase A4 (GSTA4 were not altered. An in vitro evaluation using the recombinant protein revealed that FABP4 itself functions as a scavenger protein against hydrogen peroxide (H2O2. FABP4-knockdown resulted in a significant lowering of cell viability of 3T3-L1 adipocytes against H2O2 treatment. Moreover, four kinds of markers related to the ER stress response including the endoplasmic reticulum to nucleus signaling 1 (Ern1, the signal sequence receptor α (Ssr1, the ORM1-like 3 (Ormdl3, and the spliced X-box binding protein 1 (Xbp1s, were all elevated as the result of the knockdown of FABP4. Consequently, FABP4 might have a new role as an antioxidant protein against H2O2 and contribute to cytoprotection against oxidative and ER stress in adipocytes.

  16. Osteoporosis and prevention. Assessment of mineral density, geometry and biomechanics of bone by means of peripheral quantitative Computed Tomography (pQCT) in premenopausal women assuming phytoestrogens; Osteoporosi e fitoestrogeni: valutazione della densita' minerale ossea mediante tomografia computerizzata quantitativa periferica nelle donne lattoovovegetariane nella premenopausa

    Energy Technology Data Exchange (ETDEWEB)

    Di Leo, C; Tarolo, G L; Bestetti, A; Tagliabue, L; Del Sole, A; Alberti, G [Ospedale San Paolo, Milan (Italy). Servizio di Medicina Nucleare; Cestaro, B [Milan Univ., Milan (Italy). Cattedra e Scuola di Specializzazione in Medicina Nucleare; Pepe, L [ACN-L' Accessorio Nucleare, Cerro Maggiore, MI (Italy). Lab. Nucleari

    2000-04-01

    Aim of the work was to describe the noninvasive assessment of bone mineral density, geometrical and biochemical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with Mediterranean dietary intake lacking in these substances. Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated with peripheral quantitative computed tomography (pQCT) at the distal radius of the non dominant forearm. pQCT showed higher bone mineral density (total and trabecular) and SSI values in premenopausal with dietary intake of phytoestrogens. Despite the lack of statistical significance, these preliminary results, should further support the few literature findings about the potential role of phytoestrogens consumption in preventing trabecular bone loss. However, further studies are warranted to evaluate definitively postmenopausal osteoporosis. [Italian] Scopo del lavoro e' quello di studiare in modo non-invasivo la densita' minerale, le caratteristiche geometriche e biomeccaniche dell'osso in donne lattoovovegetariane nella premenopausa che assumevano con la dieta fitoestrogeni e confrontare questi dati con quelli di donne anch'esse in premenopausa, con dieta di tipo mediterraneo assolutamente priva di questi elementi con azione simil-ormonale. La densita' minerale, le proprieta' geometriche meccaniche dell'osso sono state valutate a livello del radio ultradistale non dominante mediante tomografia computerizzata (TC) quantitativa periferica, che nelle donne in premenopausa con dieta ricca di fitoestrogeni ha evidenziato valori della densita' minerale ossea totale, trabecolare e di resistenza ossea piu' elevati, anche se in modo non significativo, rispetto a quelli dei controlli con dieta mediterranea. Questi risultati preliminari suggerirebbero come l'assunzione quotidiana di fitoestrogeni attraverso la soia potrebbe accompagnarsi a un maggiore

  17. Osteoporosis and prevention. Assessment of mineral density, geometry and biomechanics of bone by means of peripheral quantitative Computed Tomography (pQCT) in premenopausal women assuming phytoestrogens; Osteoporosi e fitoestrogeni: valutazione della densita' minerale ossea mediante tomografia computerizzata quantitativa periferica nelle donne lattoovovegetariane nella premenopausa

    Energy Technology Data Exchange (ETDEWEB)

    Di Leo, C.; Tarolo, G.L.; Bestetti, A.; Tagliabue, L.; Del Sole, A.; Alberti, G. [Ospedale San Paolo, Milan (Italy). Servizio di Medicina Nucleare; Cestaro, B. [Milan Univ., Milan (Italy). Cattedra e Scuola di Specializzazione in Medicina Nucleare; Pepe, L. [ACN-L' Accessorio Nucleare, Cerro Maggiore, MI (Italy). Lab. Nucleari

    2000-04-01

    Aim of the work was to describe the noninvasive assessment of bone mineral density, geometrical and biochemical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with Mediterranean dietary intake lacking in these substances. Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated with peripheral quantitative computed tomography (pQCT) at the distal radius of the non dominant forearm. pQCT showed higher bone mineral density (total and trabecular) and SSI values in premenopausal with dietary intake of phytoestrogens. Despite the lack of statistical significance, these preliminary results, should further support the few literature findings about the potential role of phytoestrogens consumption in preventing trabecular bone loss. However, further studies are warranted to evaluate definitively postmenopausal osteoporosis. [Italian] Scopo del lavoro e' quello di studiare in modo non-invasivo la densita' minerale, le caratteristiche geometriche e biomeccaniche dell'osso in donne lattoovovegetariane nella premenopausa che assumevano con la dieta fitoestrogeni e confrontare questi dati con quelli di donne anch'esse in premenopausa, con dieta di tipo mediterraneo assolutamente priva di questi elementi con azione simil-ormonale. La densita' minerale, le proprieta' geometriche meccaniche dell'osso sono state valutate a livello del radio ultradistale non dominante mediante tomografia computerizzata (TC) quantitativa periferica, che nelle donne in premenopausa con dieta ricca di fitoestrogeni ha evidenziato valori della densita' minerale ossea totale, trabecolare e di resistenza ossea piu' elevati, anche se in modo non significativo, rispetto a quelli dei controlli con dieta mediterranea. Questi risultati preliminari suggerirebbero come l'assunzione quotidiana di fitoestrogeni

  18. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Directory of Open Access Journals (Sweden)

    Haule Emmanuel E

    2012-10-01

    Full Text Available Abstract Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich. Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae, Maytenus senegalensis (Lam. Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922, Salmonella typhi (NCTC 8385, Vibrio cholerae (clinical isolate, and Klebsiella pneumoniae (clinical isolate using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole

  19. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Science.gov (United States)

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual

  20. Moderate activation of IKK2-NF-kB in unstressed adult mouse liver induces cytoprotective genes and lipogenesis without apparent signs of inflammation or fibrosis.

    Science.gov (United States)

    Lu, Hong; Lei, Xiaohong; Zhang, Qinghao

    2015-07-30

    liver, which was associated with higher lipogenic factors Pparγ, Lxr, Fasn, Scd1, and CD36. In summary, moderate activation of IKK2-NF-kB in unstressed adult mouse hepatocytes produces a cytoprotective gene expression profile and induces lipogenesis without apparent signs of inflammation or fibrosis, likely due to strong activation of the anti-inflammatory IKK1-RelB alternative NF-kB pathway as well as the Lxr.

  1. Synergistic Antimicrobial Activities Of Phytoestrogens In Crude ...

    African Journals Online (AJOL)

    African Journal of Traditional, Complementary and Alternative Medicines ... isolated from medicinal plants have doubled in the last decade worldwide. ... except Streptococcus pneumoniae and Staphylococcus aureus respectively, while the ...

  2. Synergistic Antimicrobial Activities Of Phytoestrogens In Crude ...

    African Journals Online (AJOL)

    Ethanolic, methanolic and aqueous extracts of both leaves were studied for their in-vitro synergistic antimicrobial activity against both Gram positive and Gram negative micro-organisms, and Yeast using Agar diffusion method. The GC-MS phytochemical screening of methanolic extract showed that the major compounds in ...

  3. The Cytoprotective Effects of E-α-(4-Methoxyphenyl-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC--A Novel and Non-Cytotoxic HO-1 Inducer.

    Directory of Open Access Journals (Sweden)

    Kai B Kaufmann

    Full Text Available Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1, is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  4. Structures, physicochemical and cytoprotective properties of new oxidovanadium(IV) complexes -[VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O

    Science.gov (United States)

    Drzeżdżon, Joanna; Jacewicz, Dagmara; Wyrzykowski, Dariusz; Inkielewicz-Stępniak, Iwona; Sikorski, Artur; Tesmar, Aleksandra; Chmurzyński, Lech

    2017-09-01

    New oxidovanadium(IV) complexes with a modification of the ligand in the VO2+ coordination sphere were synthesized. [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O were obtained as dark green crystals and grey-green powder, respectively (mIDA = N-methyliminodiacetic anion, IDA = iminodiacetic anion, dmbipy = 4,4‧-dimethoxy-2,2‧-dipyridyl). The crystal structure of [VO(mIDA)(dmbipy)]·1.5H2O has been determined by the X-ray diffraction method. The studies of structure of [VO(mIDA)(dmbipy)]•1.5H2O have shown that this compound occurs in the crystal as two rotational conformers. Furthermore, the stability constants of [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O complexes in aqueous solutions were studied by using the potentiometric titration method and, consequently, determined using the Hyperquad2008 program. Moreover, the title complexes were investigated as antioxidant substances. The impact of the structure modification in the VO2+ complexes on the radical scavenging activity has been studied. The ability to scavenge the superoxide radical by two complexes - [VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O was studied by cyclic voltammetry (CV) and nitrobluetetrazolium (NBT) methods. The title complexes were also examined by the spectrophotometric method as scavengers of neutral organic radical - 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and radical cation - 2,2'-azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS•+). Furthermore, the biological properties of two oxidovanadium(IV) complexes were investigated in relation to its cytoprotective properties by the MTT and LDH tests based on the hippocampal HT22 neuronal cell line during the oxidative damage induced by hydrogen peroxide. Finally, the results presented in this paper have shown that the both new oxidovanadium(IV) complexes with the 4,4‧-dimethoxy-2,2‧-dipyridyl ligand can be treated as the cytoprotective substances.

  5. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules

    Directory of Open Access Journals (Sweden)

    Das Undurti N

    2008-10-01

    Full Text Available Abstract Lowering plasma low density lipoprotein-cholesterol (LDL-C, blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a β blocker, and an angiotensin converting enzyme (ACE inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by ~80%. Essential fatty acids (EFAs and their long-chain metabolites: γ-linolenic acid (GLA, dihomo-GLA (DGLA, arachidonic acid, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA and other products such as prostaglandins E1 (PGE1, prostacyclin (PGI2, PGI3, lipoxins (LXs, resolvins, protectins including neuroprotectin D1 (NPD1 prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-γ ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of ω-3 and ω-6 fatty acids and the co

  6. Cytoprotection with amifostine in radiotherapy or combined radio-chemotherapy of head and neck cancer; Zytoprotektion mit Amifostin in der Strahlentherapie bzw. Strahlen-/Chemotherapie von Kopf-Hals-Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Altmann, S.; Hoffmanns, H. [Krankenhaus Maria-Hilf, Moenchengladbach (Germany). Strahlentherapie und Radiologische Onkologie

    1999-11-01

    Background: A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments. The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer. Patients and methods: Twenty-three patients with advanced head and neck cancer, mainly Stage III and IV, were treated with preoperative radiation (n=1), pre- as well as postoperative radiotherapy (n=5), postoperative radiation (n=9) or combined postoperative radio-chemotherapy (n=6). Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes. The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients. Results: In 15 patients (65%) of the amifostine group, therapy induced side effects such as mucositis and dermatitis of WHO Grade {<=}2 were detected, requiring interruptions of the radiotherapy (mean: 6.5, maximum 17 days). No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group. Significantly more acute toxicity was detected in the historical control group. Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients (41%). The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients (88%) (mean: 16, maximum 40 days; p=0.0016). Conclusion: The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer, allowing for a better adherence to the planned radiation time schedule. (orig.) [German] Hintergrund: Zahlreiche experimentelle und klinische Daten belegen die zytoprotektive Wirkung von Amifostin auf gesundes Gewebe bei Anwendung verschiedener antineoplastischer

  7. Phytoestrogenic property of Labisia pumila for use as an estrogen ...

    African Journals Online (AJOL)

    Melissa

    Labisia pumila (LP), also known as Kacip Fatimah has been used by Malay women for generations for conditions related to menopausal symptoms. Though, there has been no scientific-based evidence for its efficacy as an estrogen replacement therapy (ERT), LP's use continues to be on the rise. This could be seen with ...

  8. Modulatory Effect of Phytoestrogens and Curcumin on Induction of ...

    African Journals Online (AJOL)

    Recent studies on the induction of ANXA1 expression have shown that chemically similar estrogen hormones also have role in the induction of the ANXA1. In studies carried out previously, researchers had demonstrated that in human lymphoblastic CCRF-CEM cell line, estrogen hormone and 17 β-estradiol (E2β) induced ...

  9. Vegetables, fruits and phytoestrogens in the prevention of diseases

    Directory of Open Access Journals (Sweden)

    Heber David

    2004-04-01

    Full Text Available The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer, and diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of ageing. These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits. Many phytochemicals are colourful, and recommending a wide array of colourful fruits and vegetables is an easy way to communicate increased diversity of intake to the consumer. For example, red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease. Green foods, including broccoli, Brussels sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer. Garlic and other white-green foods in the onion family contain allyl sulphides which may inhibit cancer cell growth. Other bioactive substances in green tea and soybeans have health benefits as well. Consumers are advised to ingest one serving of each of the seven colour groups daily, putting this recommendation within the United States National Cancer Institute and American Institute for Cancer Research guidelines of five to nine servings per day. Grouping plant foods by colour provides simplification, but it is also important as a method to help consumers make wise food choices and promote health.

  10. Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Jeong, Hye Gwang

    2010-01-01

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent Gβ1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gβ1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems.

  11. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity

    Czech Academy of Sciences Publication Activity Database

    Pyszková, M.; Biler, M.; Biedermann, David; Valentová, Kateřina; Kuzma, Marek; Vrba, J.; Ulrichová, J.; Sokolová, Romana; Mojovic, M.; Popovic-Bijelic, A.; Kubala, M.; Trouillas, P.; Křen, Vladimír; Vacek, J.

    2016-01-01

    Roč. 90, JAN 2016 (2016), s. 114-125 ISSN 0891-5849 R&D Projects: GA MŠk(CZ) LD14096; GA ČR(CZ) GA15-03037S Grant - others:MŠMT(CZ) LO1024 Institutional support: RVO:61388971 ; RVO:61388955 Keywords : Flavonolignans * Antioxidants * Oxidation Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 5.606, year: 2016

  12. Cytoprotection: Immune and Matrix Modulation of Tissue Repair

    Science.gov (United States)

    2013-04-01

    TREM-2 and DAP12, and tested them in THP -1 cells, a monocyte-like cell line  Initiated tests of additional antibodies for detection of TREM-2 and...interactions. The goal of Aim 2 is to develop an engineered tissue model (a “myobridge” for replacement of skeletal muscle) and use it as a test -bed to...Regulation Task 1 (Months 1–9) Develop and test stable, shear-resistant HMW-HA/fibrillar collagen hydrogels on dye-cut 2.9 mm nylon mesh rings

  13. Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Nishikawa

    Full Text Available Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress.

  14. Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

    Directory of Open Access Journals (Sweden)

    Davide Degli Esposti

    2012-01-01

    Full Text Available The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.

  15. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

    Science.gov (United States)

    Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

    2013-12-01

    Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

  16. In vitro Models of Laser Induced Injury: Pathophysiology and Cytoprotection

    National Research Council Canada - National Science Library

    Bowman, Phillip D; Schuschereba, Steven T

    2007-01-01

    Lasers generating predominantly thermal energy are used in medicine and research for a variety of purposes including surgical excision, pan retinal photocoagulation for treating diabetic retinopathy...

  17. A novel antilithiatic protein from Tribulus terrestris having cytoprotective potency.

    Science.gov (United States)

    Aggarwal, Anshu; Tandon, Simran; Singla, Surinder Kumar; Tandon, Chanderdeep

    2012-08-01

    Adhesion of calcium oxalate (CaOx) crystals to kidney cells is a key event in kidney stones associated with marked hyperoxaluria. As the propensity of stone recurrence and persistent side effects are not altered by surgical techniques available, phytotherapeutic agents could be useful as an adjuvant therapy. The present study is aimed at examining the antilithiatic potency of the protein biomolecules of Tribulus terrestris, a plant which is a common constituent of herbal marketed preparations to treat urolithiasis. Various biochemical methods with mass spectrometry were used to purify and characterize the purified protein. The protective potency of the protein was tested on the oxalate induced injury on renal epithelial cell lines (NRK 52E). An antilithiatic protein having molecular weight of ~ 60kDa was purified. This purified protein showed similarities with Carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints in MASCOT search engine. An EF hand domain was identified in CCD7 by SCAN PROSITE. Presence of an EF hand domain, a characteristic feature of calcium binding proteins and a role in the synthesis of retinol which is transported by retinol binding protein, a protein found in kidney stone matrix; of CCD7 support the role of TTP as an antilithiatic protein. The protective potency of TTP on NRK 52E was quite comparable to the aqueous extract of cystone. Our findings suggest that this purified protein biomolecule from Tribulus terrestris could open new vista in medical management of urolithiasis.

  18. Suplementação com ácido ascórbico tem efeito citoprotetor na cirrose biliar secundária: estudo experimental em ratos jovens Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

    Directory of Open Access Journals (Sweden)

    Cynthia R. Matos Silva Passoni

    2008-12-01

    Full Text Available OBJETIVO: Testar se a suplementação com ácido ascórbico tem algum afeito citoprotetor em um modelo de cirrose biliar secundária em ratos jovens. MÉTODOS: Foram estudados 40 ratos Wistar desmamados no 21º dia pós-natal. Cada grupo de 10 foi submetido a um dos seguintes quatro tratamentos, até o 49º dia pós-natal, quando foram submetidos a eutanásia: 1 LC - ligadura dupla e ressecção do ducto biliar comum e administração diária de ácido ascórbico [100 mg/g de peso corporal (pc]; 2 LA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc; 3 SC - operação simulada e administração diária de ácido ascórbico (100 mg/g pc; 4 SA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc. Os ratos eram pesados diariamente. No 27º dia pós-operatório, eles receberam injeção intraperitoneal de 1,5 mg/g pc de pentobarbital sódico, e o tempo de sono induzido pelo pentobarbital foi medido. Coletou-se sangue para determinação de atividade sérica de alanina aminotransferase e de aspartato aminotransferase, níveis de albumina e globulina séricas, e o fígado foi analisado quanto à conteúdo de água e gordura. Os dados foram submetidos à ANOVA two-way, e comparações pareadas entre grupos foram testadas com o método de SNK. O nível de significância foi estabelecido em 0,05. RESULTADOS: A suplementação com ácido ascórbico atenuou os efeitos da colestase: reduziu o tempo de anestesia pelo pentobarbital, globulina sérica e o conteúdo de gordura no fígado. CONCLUSÕES: Nossos resultados corroboram a hipótese de que a suplementação com ácido ascórbico tem um efeito citoprotetor na cirrose biliar secundária.OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal

  19. Gastrointestinal metabolism of phytoestrogens in lactating dairy cows fed silages with different botanical composition

    DEFF Research Database (Denmark)

    Njåstad, K. M.; Adler, S. A.; Hansen-Møller, J.

    2014-01-01

    extensively metabolized in the rumen on all diets, and the recovery of formononetin and daidzein in omasum, mainly as equol, averaged 0.11. mg/mg. The apparent intestinal metabolism was less severe as, on average, 0.29. mg/mg of the omasal flow was recovered in feces. The plant lignans were also strongly...

  20. Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

    Directory of Open Access Journals (Sweden)

    Seok Choi

    2014-12-01

    Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

  1. Effects of Nutrition Relevant Mixtures of Phytoestrogens on Steroidogenesis, Aromatase, Estrogen, and Androgen Activity

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Engell-Kofoed, Anders Elleby; Sonne-Hansen, Katrine

    2010-01-01

    in the MCF7 cells of the isoflavonoid mixture and coumestrol was supported by an observed increase in progesterone receptor protein expression as well as a decreased ER expression. Overall, the results support that nutrition-relevant concentrations of PEs both alone and in mixtures possess various endocrine...

  2. Estrogenic effect of the phytoestrogen biochanin A in zebrafish, Danio rerio, and brown trout, Salmo trutta.

    Science.gov (United States)

    Holbech, Henrik; Schröder, Kristoffer D; Nielsen, Marie L; Brande-Lavridsen, Nanna; Holbech, Bente Frost; Bjerregaard, Poul

    2013-11-15

    Isoflavones with estrogenic activity produced in Fabaceae plants are known to leach from agricultural areas to freshwater systems, but the effect of waterborne isoflavones in fish has not been thoroughly characterized. Therefore, the estrogenic effect of waterborne biochanin A was investigated in zebrafish (Danio rerio) and juvenile brown trout (Salmo trutta). Exposure of juvenile brown trout to 10 μg biochanin AL(-1) or higher caused marked vitellogenin induction after 9-10 days of exposure and so did exposure to 186 μg biochanin AL(-1) for 6h. Following 8d of exposure, a NOEC for induction of vitellogenin production in male zebrafish was 70 and LOEC 114 μg biochanin AL(-1). Exposure to 209 μg biochanin AL(-1) from hatch to 60 days post hatch (dph) caused a skewing of the sex ratio toward more phenotypic female zebrafish, but did not cause induction of vitellogenin in male and undifferentiated fish. (1) biochanin A elicits estrogenic effects in trout at environmentally realistic concentrations, (2) brown trout plasma vitellogenin concentrations respond to lower biochanin A exposure concentrations than vitellogenin concentrations in zebrafish homogenates and (3) concerning vitellogenin induction, the hypothesis should be tested if short term tests with zebrafish may show a higher sensitivity than partial life cycle tests. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat.

    Science.gov (United States)

    Qi, Shanshan; Zheng, Hongxing

    2017-06-01

    This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P silicon have synergistic effects on bone formation in ovariectomized rats.

  4. Suppression of dendritic cells' maturation and functions by daidzein, a phytoestrogen

    International Nuclear Information System (INIS)

    Yum, Min Kyu; Jung, Mi Young; Cho, Daeho; Kim, Tae Sung

    2011-01-01

    Isoflavones are ubiquitous compounds in foods and in the environment in general. Daidzein and genistein, the best known of isoflavones, are structurally similar to 17β-estradiol and known to exert estrogenic effects. They also evidence a broad variety of biological properties, including antioxidant, anti-carcinogenic, anti-atherogenic and anti-osteoporotic activities. Previously, daidzein was reported to increase the phagocytic activity of peritoneal macrophages and splenocyte proliferation, and to inhibit nitric oxide (NO) production in macrophages. However, its potential impacts on immune response in dendritic cells (DCs), antigen-presenting cells that link innate and adaptive immunity, have yet to be clearly elucidated. In this study, we evaluated the effects of isoflavones on the maturation and activation of DCs. Isoflavones (formononetin, daidzein, equol, biochanin A, genistein) were found to differentially affect the expression of CD86, a costimulatory molecule, on lipopolysaccharide (LPS)-stimulated DCs. In particular, daidzein significantly and dose-dependently inhibited the expression levels of maturation-associated cell surface markers including CD40, costimulatory molecules (CD80, CD86), and major histocompatibility complex class II (I-A b ) molecule on LPS-stimulated DCs. Daidzein also suppressed pro-inflammatory cytokine production such as IL-12p40, IL-6 and TNF-α, whereas it didn't affect IL-10 and IL-1β expression. Furthermore, daidzein enhanced endocytosis and inhibited the allo-stimulatory ability of LPS-stimulated DCs on T cells, indicating that daidzein treatment can inhibit the functional maturation of DCs. These results demonstrate that daidzein may exhibit immunosuppressive activity by inhibiting the maturation and activation of DCs. -- Highlights: ► Daidzein inhibited expression of maturation-associated cell surface markers in DCs. ► Daidzein suppressed expression of pro-inflammatory cytokines in LPS-stimulated DCs. ► Daidzein enhanced endocytosis and inhibited allo-stimulatory ability of DCs. ► Daidzein exhibited immunosuppressive activity by inhibiting the activation of DCs.

  5. Suppression of dendritic cells' maturation and functions by daidzein, a phytoestrogen

    Energy Technology Data Exchange (ETDEWEB)

    Yum, Min Kyu; Jung, Mi Young [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Cho, Daeho [Department of Life Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Tae Sung, E-mail: tskim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

    2011-12-15

    Isoflavones are ubiquitous compounds in foods and in the environment in general. Daidzein and genistein, the best known of isoflavones, are structurally similar to 17{beta}-estradiol and known to exert estrogenic effects. They also evidence a broad variety of biological properties, including antioxidant, anti-carcinogenic, anti-atherogenic and anti-osteoporotic activities. Previously, daidzein was reported to increase the phagocytic activity of peritoneal macrophages and splenocyte proliferation, and to inhibit nitric oxide (NO) production in macrophages. However, its potential impacts on immune response in dendritic cells (DCs), antigen-presenting cells that link innate and adaptive immunity, have yet to be clearly elucidated. In this study, we evaluated the effects of isoflavones on the maturation and activation of DCs. Isoflavones (formononetin, daidzein, equol, biochanin A, genistein) were found to differentially affect the expression of CD86, a costimulatory molecule, on lipopolysaccharide (LPS)-stimulated DCs. In particular, daidzein significantly and dose-dependently inhibited the expression levels of maturation-associated cell surface markers including CD40, costimulatory molecules (CD80, CD86), and major histocompatibility complex class II (I-A{sup b}) molecule on LPS-stimulated DCs. Daidzein also suppressed pro-inflammatory cytokine production such as IL-12p40, IL-6 and TNF-{alpha}, whereas it didn't affect IL-10 and IL-1{beta} expression. Furthermore, daidzein enhanced endocytosis and inhibited the allo-stimulatory ability of LPS-stimulated DCs on T cells, indicating that daidzein treatment can inhibit the functional maturation of DCs. These results demonstrate that daidzein may exhibit immunosuppressive activity by inhibiting the maturation and activation of DCs. -- Highlights: Black-Right-Pointing-Pointer Daidzein inhibited expression of maturation-associated cell surface markers in DCs. Black-Right-Pointing-Pointer Daidzein suppressed expression of pro-inflammatory cytokines in LPS-stimulated DCs. Black-Right-Pointing-Pointer Daidzein enhanced endocytosis and inhibited allo-stimulatory ability of DCs. Black-Right-Pointing-Pointer Daidzein exhibited immunosuppressive activity by inhibiting the activation of DCs.

  6. Dual Effects of Phytoestrogens Result in U-Shaped Dose-Response Curves

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Fernández, Mariana F.; Petersen, Jørgen Holm

    2002-01-01

    Endocrine disruptors can affect the endocrine system without directly interacting with receptors, for example, by interfering with the synthesis or metabolism of steroid hormones. The aromatase that converts testosterone to 17beta-estradiol is a possible target. In this paper we describe an assay...

  7. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Siti Rosmani Md Zin

    2013-01-01

    Full Text Available OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i a control group that received vehicle (distilled water and Tween 80; (ii a group treated with 10 mg/kg body weight (BW of Genistein (Gen 10; and (iii a group treated with a higher dose of Genistein (Gen 100. The rats were treated daily for three weeks from postnatal day 22 (P22 to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05. These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

  8. Gastroprotective, cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol induced damage

    OpenAIRE

    Ozbayer, Cansu; Kurt, Hulyam; Ozdemir, Zeynep; Tuncel, Tunc; Moheb Saadat, Selva; Burukoglu, Dilek; Senturk, Hakan; Degirmenci, Irfan; Gunes, Hasan Veysi

    2013-01-01

    Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a traditional herb used for many diseases and it has also effects as an antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and kidney disorders induced by ethanol. In our experiment, 2–3 month old male Sprague–Dawley rats were used...

  9. Cytoprotective Effect of American Ginseng in a Rat Ethanol Gastric Ulcer Model

    Directory of Open Access Journals (Sweden)

    Chi-Chang Huang

    2013-12-01

    Full Text Available Panax quinquefolium L. (American Ginseng, AG is one of the most popular herbal medicines in the World. We aimed to investigate whether chronic (28-day supplementation with AG could protect against ethanol-induced ulcer in gastric tissue. Furthermore, we investigated the possible molecular mechanisms leading to AG-mediated gastric mucosal protection. We randomized 32 male Wistar rats into four groups for treatment (n = 8 per group: supplementation with water (vehicle and low-dose (AG-1X, medium-dose (AG-2X and high-dose (AG-5X AG at 0, 250, 500, and 1250 mg/kg, respectively. In the first experiment, animals were fed vehicle or AG treatments for 4 weeks. At day 29, 75% ethanol was given orally to each animal at 10 mL/kg to induce gastric ulceration for 2 h. In a second experiment, animals were pretreated orally with each treatment for 1 hr before a single oral administration of ethanol (70%, 10 mL/kg. Trend analysis revealed that AG treatments inhibited ethanol-induced gastric mucosal damage. AG supplementation dose-dependently decreased the pro-inflammatory levels of interleukin 1β and cyclooxygenase 2 and the expression of pro-apoptotic proteins tBid, cytochrome C, and caspases-9 and -3 and increased the levels of anti-apoptotic proteins Bcl-2, Bcl-xL and p-Bad. AG could have pharmacological potential for treating gastric ulcer.

  10. Cytoprotection with amifostine in the simultaneous radio-chemotherapy of recurrent head and neck cancer

    International Nuclear Information System (INIS)

    Buentzel, J.; Weinaug, R.; Kuettner, K.

    1999-01-01

    Purpose: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). Patients and methods: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20x1.5 Gy, Carboplatin 70 mg/m 2 BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tumor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. Results: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation in 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: Side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: Mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. Conclusion: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region. (orig.) [de

  11. A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

    International Nuclear Information System (INIS)

    Dinkova-Kostova, Albena T.; Jenkins, Stephanie N.; Wehage, Scott L.; Huso, David L.; Benedict, Andrea L.; Stephenson, Katherine K.; Fahey, Jed W.; Liu Hua; Liby, Karen T.; Honda, Tadashi; Gribble, Gordon W.; Sporn, Michael B.; Talalay, Paul

    2008-01-01

    Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm 2 /session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality

  12. Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

    Science.gov (United States)

    Salamanna, F; Frizziero, A; Pagani, S; Giavaresi, G; Curzi, D; Falcieri, E; Marini, M; Abruzzo, P M; Martini, L; Fini, M

    2015-02-01

    The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.

  13. Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection

    Czech Academy of Sciences Publication Activity Database

    Bai, M.; Vozdek, R.; Hnízda, Aleš; Jiang, C.; Wang, B.; Kuchař, L.; Li, T.; Zhang, Y.; Wood, C.; Feng, L.; Dang, Y.; Ma, D. K.

    2018-01-01

    Roč. 9, Mar 1 (2018), č. článku 897. ISSN 2041-1723 R&D Projects: GA ČR GA15-06582S Institutional support: RVO:61388963 Keywords : unfolded protein response * neurotrophic factor MANF * Caenorhabditis elegans Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 12.124, year: 2016 https://www.nature.com/articles/s41467-018-03355-0

  14. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.; Kuijpers-Jagtman, A.M.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between

  15. Cytoprotection by fructose and other ketohexoses during bile salt-induced apoptosis of hepatocytes.

    Science.gov (United States)

    Zeid, I M; Bronk, S F; Fesmier, P J; Gores, G J

    1997-01-01

    Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt-induced necrosis, the effect of fructose on bile salt-induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt-induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)-induced apoptosis in a concentration-dependent manner with a maximum inhibition of 72% +/- 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to effects, alterations in the expression of bcl-2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt-induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt-induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose-sensitive pathways appear to initiate both bile salt-induced cell apoptosis and necrosis, whereas dissimilar, pH-sensitive, effector mechanisms execute these two different cell death processes.

  16. Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats

    Science.gov (United States)

    Suttorp, Christiaan M.; Xie, Rui; Lundvig, Ditte M. S.; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C.; Wagener, Frank A. D. T. G.

    2016-01-01

    Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, “fast” and “slow” tooth movers during orthodontic treatment. PMID:27486402

  17. Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats

    NARCIS (Netherlands)

    Suttorp, C.M.; Xie, R.; Lundvig, D.M.S.; Kuijpers-Jagtman, A.M.; Uijttenboogaart, J.T.; Rheden, R.E.M. van; Maltha, J.C.; Wagener, F.A.D.T.G.

    2016-01-01

    Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root

  18. [Molecular mechanisms of cytoprotective action of the plant proanthocyanidins in gastric lesions].

    Science.gov (United States)

    Zaiachkivs'ka, O S

    2006-01-01

    The molecular defence mechanisms against ethanol- and stress-induced (WRS) gastric lesions under the action of plant proanthocyanidins from grapefruit-seed extract (GSE) were investigated. Pre-treatment with GSE (8-64 mg/kg/day) in dose-dependent manner attenuated gastric lesions induced by 100% ethanol and WRS; the doses of GCE reducing these lesions by 50% (ID50) were 28 and 36 mg/kg/day, respectively and this protective effect was similar to that obtained with PGE2 analogue. Lesions reduction was also accompanied by improvement of gastric blood flow, antiradical action, increased mucosal generation of PGE2, antioxidant activity.

  19. Insulin-secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis (Sweet Broomweed).

    Science.gov (United States)

    Latha, Muniappan; Pari, Leelavinothan; Sitasawad, Sandhya; Bhonde, Ramesh

    2004-09-03

    Scoparia dulcis (Sweet Broomweed) has been documented as a traditional treatment of diabetes. The administration of an aqueous extract of Scoparia dulcis at a dose of 200 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in streptozotocin diabetic rats at the end of 15 days treatment. The insulin secretagogue action of Scoparia dulcis plant extract (SPEt) was further investigated using isolated pancreatic islets from mice. SPEt at a dose of 10 microg/ml evoked 6.0 fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. In addition the effect of SPEt on streptozotocin induced cell death and nitric oxide (NO) in terms of nitrite production were also examined. SPEt protected against streptozotocin- mediated cytotoxicity (88%) and NO production in rat insulinoma cell line (RINm5F). Above results suggest the glucose lowering effect of SPEt to be associated with potentiation of insulin release from pancreatic islets. Our results revealed the possible therapeutic value of Scoparia dulcis for the better control, management and prevention of diabetes mellitus progression.

  20. Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells.

    Directory of Open Access Journals (Sweden)

    Tingting Jiang

    Full Text Available Oxidative stress is a contributing factor to the development and progression of diabetic retinopathy, a leading cause of blindness in people at working age worldwide. Recent studies showed that Müller cells play key roles in diabetic retinopathy and produce vascular endothelial growth factor (VEGF that regulates retinal vascular leakage and proliferation. Melatonin is a potent antioxidant capable of protecting variety of retinal cells from oxidative damage. In addition to the pineal gland, the retina produces melatonin. In the current study, we investigated whether melatonin protects against hyperglycemia-induced oxidative injury to Müller cells and explored the potential underlying mechanisms. Our results show that both melatonin membrane receptors, MT1 and MT2, are expressed in cultured primary Müller cells and are upregulated by elevated glucose levels. Both basal and high glucose-induced VEGF production was attenuated by melatonin treatment in a dose-dependent manner. Furthermore, we found that melatonin is a potent activator of Akt in Müller cells. Our findings suggest that in addition to functioning as a direct free radical scavenger, melatonin can elicit cellular signaling pathways that are protective against retinal injury during diabetic retinopathy.

  1. Immune effector mechanisms of the nitric oxide pathway in malaria: cytotoxicity versus cytoprotection

    Directory of Open Access Journals (Sweden)

    Hossein Nahrevanian

    Full Text Available Nitric oxide (NO is thought to be an important mediator and critical signaling molecule for malaria immunopathology; it is also a target for therapy and for vaccine. Inducible nitric oxide synthase (iNOS is synthesized by a number of cell types under inflammatory conditions. The most relevant known triggers for its expression are endotoxins and cytokines. To date, there have been conflicting reports concerning the clinical significance of NO in malaria. Some researchers have proposed that NO contributes to the development of severe and complicated malaria, while others have argued that NO has a protective role. Infection with parasites resistant to the microbicidal action of NO may result in high levels of NO being generated, which could then damage the host, instead of controlling parasitemia. Consequently, the host-parasite interaction is a determining factor for whether the parasite is capable of stimulating NO production; the role of NO in resistance to malaria appears to be strain specific. It is known that NO and/or its related molecules are involved in malaria, but their involvement is not independent of other immune events. NO is an important, but possibly not an essential contributor to the control of acute-phase malaria infection. The protective immune responses against malaria parasite are multifactorial; however, they necessarily involve final effector molecules, including NO, iNOS and RNI.

  2. PRAS40 is an integral regulatory component of erythropoietin mTOR signaling and cytoprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Zhong Chong

    Full Text Available Emerging strategies that center upon the mammalian target of rapamycin (mTOR signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO, a novel agent for nervous system disorders, prevents apoptotic SH-SY5Y cell injury in an oxidative stress model of oxygen-glucose deprivation through phosphatidylinositol-3-kinase (PI 3-K/protein kinase B (Akt dependent activation of mTOR signaling and phosphorylation of the downstream pathways of p70 ribosomal S6 kinase (p70S6K, eukaryotic initiation factor 4E-binding protein 1 (4EBP1, and proline rich Akt substrate 40 kDa (PRAS40. PRAS40 is an important regulatory component either alone or in conjunction with EPO signal transduction that can determine cell survival through apoptotic caspase 3 activation. EPO and the PI 3-K/Akt pathways control cell survival and mTOR activity through the inhibitory post-translational phosphorylation of PRAS40 that leads to subcellular binding of PRAS40 to the cytoplasmic docking protein 14-3-3. However, modulation and phosphorylation of PRAS40 is independent of other protective pathways of EPO that involve extracellular signal related kinase (ERK 1/2 and signal transducer and activator of transcription (STAT5. Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise.

  3. Cytoprotective Effect of Lactobacillus crispatus CTV-05 against Uropathogenic E. coli

    Directory of Open Access Journals (Sweden)

    Daniel S. C. Butler

    2016-03-01

    Full Text Available The vaginal flora consists of a subset of different lactic acid producing bacteria, typically creating a hostile environment for infecting pathogens. However, the flora can easily be disrupted, creating a favorable milieu for uropathogenic Escherichia coli (UPEC, making it possible to further infect the urinary system via the urethra. Probiotic use of different lactobacilli to restore the normal flora of the vagina has been proposed as a potential prophylactic treatment against urinary tract infections. This project evaluated the protective- and anti-inflammatory roles of the probiotic Lactobacillus crispatus strain CTV-05 in an in vitro system. The inflammatory response and the cytotoxic effect were studied by Enzyme-linked immunosorbent assays and by trypan blue exclusion of cells inoculated with L. crispatus CTV-05 and comparing it to non-infected controls and UPEC infected cells. L. crispatus CTV-05 showed no cytotoxicity to vaginal epithelial cells compared to non-infected controls and provided significant protection against UPEC infection (p < 0.05. Further more, L. crispatus CTV-05 did not create a pro-inflammatory response in vitro, with no significant increase of IL-1β or IL-6. These results demonstrate the protective effect of using L. crispatus CTV-05 as a probiotic treatment to reduce the risk of recurrent urinary tract infections.

  4. Cytoprotective Role of Nrf2 in Electrical Pulse Stimulated C2C12 Myotube.

    Directory of Open Access Journals (Sweden)

    Masaki Horie

    Full Text Available Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2 transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.

  5. Fullerene C-60 with cytoprotective and cytotoxic potential : Prospects as a novel treatment agent in Dermatology?

    NARCIS (Netherlands)

    Rondags, Angelica; Yuen, Wing Yan; Jonkman, Marcel F.; Horvath, Barbara

    It is known that an excess amount of (oxygen) radicals in the skin can lead to (local cellular) oxidative stress. From one side, oxidative stress can contribute to the existence of various (inflammatory) skin diseases such as acne vulgaris and alopecia, as well as to accelerated photo-ageing of the

  6. Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis.

    Directory of Open Access Journals (Sweden)

    Oksana Zayachkivska

    Full Text Available Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett's esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively. Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.

  7. Curcumin induces differential expression of cytoprotective enzymes but similar apoptotic responses in fibroblasts and myofibroblasts

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.A.; Kuijpers-Jagtman, A.M.; Hoff, J.W. Von den; Wagener, F.A.D.T.G.

    2015-01-01

    Excessive extracellular matrix (ECM) deposition and tissue contraction after injury can lead to esthetic and functional problems. Fibroblasts and myofibroblasts activated by transforming growth factor (TGF)-beta1 play a key role in these processes. The persistence of (myo)fibroblasts and their

  8. Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy

    Science.gov (United States)

    Kirk, Diana K.; Gopalakrishnan, Sandeep; Schmitt, Heather; Abroe, Betsy; Stoehr, Michele; Dubis, Adam; Carroll, Joseph; Stone, Jonathan; Valter, Krisztina; Eells, Janis

    2013-03-01

    Irradiation by light in the far-red to near-infrared (NIR) region of the spectrum (photobiomodulation, PBM) has been demonstrated to attenuate the severity of neurodegenerative disease in experimental and clinical studies. The purpose of this study was to test the hypothesis that 670 nm PBM would protect against the loss of retinal function and improve photoreceptor survival in a rodent model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated once per day with a 670 nm LED array (180 sec treatments at 50 mW/cm2; fluence 9 joules/cm2) (Quantum Devices Inc., Barneveld WI) from postnatal day (p) 16-20 or from p10-20. Sham-treated rats were restrained, but not exposed to NIR light. The status of the retina was determined at p22 by assessment of mitochondrial function, oxidative stress and cell death. In a second series of studies, retinal status was assessed at p30 by measuring photoreceptor function by ERG and retinal morphology by Spectral Domain Optical Coherence Tomography (SD-OCT). 670 nm PBM increased retinal mitochondrial cytochrome oxidase activity and upregulated the retina's production of the key mitochondrial antioxidant enzyme, MnSOD. PBM also attenuated photoreceptor cell loss and improved photoreceptor function. PBM protects photoreceptors in the developing P23H retina, by augmenting mitochondrial function and stimulating antioxidant protective pathways. Photobiomodulation may have therapeutic potential, where mitochondrial damage is a step in the death of photoreceptors.

  9. Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.

    Science.gov (United States)

    Suttorp, Christiaan M; Xie, Rui; Lundvig, Ditte M S; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C; Wagener, Frank A D T G

    2016-01-01

    Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.

  10. Production of beta-glucosidase and hydrolysis of isoflavone phytoestrogens by Lactobacillus acidophilus, Bifidobacterium lactis, and Lactobacillus casei in soymilk.

    Science.gov (United States)

    Donkor, O N; Shah, N P

    2008-01-01

    The study determined beta-glucosidase activity of commercial probiotic organisms for hydrolysis of isoflavone to aglycones in fermenting soymilk. Soymilk made with soy protein isolate (SPI) was fermented with Lactobacillus acidophilus LAFTI L10, Bifidobacterium lactis LAFTI B94, and Lactobacillus casei LAFTI L26 at 37 degrees C for 48 h and the fermented soymilk was stored for 28 d at 4 degrees C. beta-Glucosidase activity of organisms was determined using rho-nitrophenyl beta-D-glucopyranoside as a substrate and the hydrolysis of isoflavone glycosides to aglycones by these organisms was carried out. The highest level of growth occurred at 12 h for L. casei L26, 24 h for B. lactis B94, and 36 h for L. acidophilus L10 during fermentation in soymilk. Survival after storage at 4 degrees C for 28 d was 20%, 15%, and 11% greater (P < 0.05) than initial cell counts, respectively. All the bacteria produced beta-glucosidase, which hydrolyzed isoflavone beta-glycosides to isoflavone aglycones. The decrease in the concentration of beta-glycosides and the increase in the concentration of aglycones were significant (P < 0.05) in the fermented soymilk. Increased isoflavone aglycone content in fermented soymilk is likely to improve the biological functionality of soymilk.

  11. Determination of the Marker Diarylheptanoid Phytoestrogens in Curcuma comosa Rhizomes and Selected Herbal Medicinal Products by HPLC-DAD.

    Science.gov (United States)

    Yingngam, Bancha; Brantner, Adelheid; Jinarat, Damrongsak; Kaewamatawong, Rawiwun; Rungseevijitprapa, Wandee; Suksamrarn, Apichart; Piyachaturawat, Pawinee; Chokchaisiri, Ratchanaporn

    2018-01-01

    A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and selected pharmaceutical preparations was established by using HPLC-diode array detector (DAD). The chromatographic separation of three diarylheptanoids [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was performed on a Luna C 18 analytical column using gradient elution with 0.5% acetic acid in water and acetonitrile with a flow rate of 1 mL/min and a column temperature of 35°C. The calibration curves for the analytes showed good linearity (R 2 >0.999), high precision (relative standard deviation (RSD) <2%) and acceptable recovery (98.35-103.90%, RSD <2%). The limit of detection (LOD) and limit of quantification (LOQ) were 0.06-0.22 and 0.18-0.69 µg/mL, respectively. The results of all validated parameters were within the limits according to the International Conference on Harmonization (ICH) Guidelines. The established method was successfully applied for qualitative and quantitative determination of the three constituents in different samples of C. comosa and some commercial products in capsules. The simplicity, rapidity, and reliability of the method could be useful for the fingerprint analysis and standardization of diarylheptanoids, which are responsible for the estrogenic activity in raw materials and herbal medicinal products of C. comosa.

  12. Estrogen and the Dietary Phytoestrogen Resveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Research

    Science.gov (United States)

    2009-06-01

    toxicity of a red grape wine flavonoid fraction against MCF 7 cells. Breast Cancer Res Treat 85:65 79. doi:10.1023/B: BREA.0000021048.52430.c0 10...Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid. J Agric Food Chem 52:255 260. doi:10.1021...The effect of the flavonoid diosmin, grape seed extract and red wine on the pul monary metastatic B16F10 melanoma. Histol Histopathol 20:1121 1129 Clin

  13. Estrogen and the Dietary Phytoestrogen Tesveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Research

    Science.gov (United States)

    2010-06-01

    3\\429::AID JCB8[3.0.CO;2 M 9. Hakimuddin F, Paliyath G, Meckling K (2004) Selective cyto toxicity of a red grape wine flavonoid fraction against MCF 7...of Her 2/neu. J Cell Biochem 105:585 595. doi:10.1002/jcb.21859 15. Yilmaz Y, Toledo RT (2004) Major flavonoids in grape seeds and skins: antioxidant...Vicente V, Yanez J, Alcaraz M, Castells MT, Can teras M, Benavente Garcia O, Castillo J (2005) The effect of the flavonoid diosmin, grape seed extract and

  14. Lignocellulosic biorefinery for waste-free manufacturing of phytoestrogens belonging to lignans, sugars for production of ethanol and growing medium

    Czech Academy of Sciences Publication Activity Database

    Váchalová, R.; Marešová, I.; Kolář, L.; Váchal, J.; Tříska, Jan

    2014-01-01

    Roč. 59, č. 4 (2014), s. 593-604 ISSN 1336-4561 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk(CZ) LD11016 Institutional support: RVO:67179843 Keywords : Lignocellulosic biorefinery * lignans * hydrolysis * growing media * separated substance of digestates Subject RIV: EH - Ecology, Behaviour Impact factor: 0.364, year: 2014

  15. Biochanin A, a Phytoestrogenic Isoflavone with Selective Inhibition of Phosphodiesterase 4, Suppresses Ovalbumin-Induced Airway Hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    Wun-Chang Ko

    2011-01-01

    the serum and BALF, and enhanced the total IgG2a level in the serum of these mice. The PDE4H/PDE4L value of biochanin A was calculated as >35. Biochanin A did not influence xylazine/ketamine-induced anesthesia. Biochanin A (10~30 μM significantly reduced cumulative OVA (10~100 μg/mL-induced contractions in the isolated guinea pig trachealis, suggesting that it inhibits degranulation of mast cells. In conclusion, red clover containing biochanin A has the potential for treating allergic asthma and COPD.

  16. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    NARCIS (Netherlands)

    Seppen, Jurgen

    2012-01-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by

  17. Estrogen and the Dietary Phytoestrogen Resveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Metastasis

    Science.gov (United States)

    2011-09-01

    S.F., and Mabry,T.J. (2002) Flavonoid effects relevant to cancer. J Nutr JID - 0404243, 132, 3482S-3489S. 40. Klinge,C.M., Blankenship,K.A...coverage of the metabolome for global metabolite profiling. Anal.Chem., 83, 2152-2161. 56. Lin,H.S. and Ho,P.C. (2009) A rapid HPLC method for the...Selective cytotoxicity of a red grape wine flavonoid fraction against MCF-7 cells. Breast Cancer Res.Treat. 2004;85:65-79. 8. Harris DM

  18. Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein.

    Science.gov (United States)

    Ismail, Nurain; Giribabu, Nelli; Muniandy, Sekaran; Salleh, Naguib

    2015-01-01

    Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause. Ovariectomised adult female rats received 25, 50 and 100 mg/kg/day genistein for seven consecutive days. At the end of the treatment, animals were sacrificed and cervix was harvested. Expression of Nhe-1, 2 and 4 mRNA were analyzed by Real-time PCR while distribution of NHE-1, 2 and 4 protein were observed by immunohistochemistry. Treatment with 50 and 100 mg/kg/day genistein caused marked increase in the levels of expression and distribution of NHE-1, 2 and 4 proteins in the endocervical epithelia. Levels of Nhe-1, 2 and 4 mRNA in the cervix were also increased. Coadministration of ICI 182 780 and genistein reduced the expression levels of NHE-1, 2 and 4 proteins and mRNAs in the cervix. Enhanced expression of NHE-1, 2 and 4 proteins and mRNAs expression in cervix under genistein influence could help to restore the cervicovaginal fluid pH that might help to prevent cervicovaginal complications related to menopause.

  19. Gas Chromatography-Mass Spectrometry Analysis of Ulva fasciata (Green Seaweed Extract and Evaluation of Its Cytoprotective and Antigenotoxic Effects

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2015-01-01

    Full Text Available The chemical composition and biological properties of Ulva fasciata aqueous-ethanolic extract were examined. Five components were identified in one fraction prepared from the extract by gas chromatography-mass spectrometry, and palmitic acid and its ethyl ester accounted for 76% of the total identified components. Furthermore, we assessed the extract’s antioxidant properties by using the DPPH, ABTS, and lipid peroxidation assays and found that the extract had a moderate scavenging effect. In an experiment involving preexposition and coexposition of the extract (1–500 µg/mL and benzo[a]pyrene (BP, the extract was found to be nontoxic to C9 cells in culture and to inhibit the cytotoxicity induced by BP. As BP is biotransformed by CYP1A and CYP2B subfamilies, we explored the possible interaction of the extract with these enzymes. The extract (25–50 µg/mL inhibited CYP1A1 activity in rat liver microsomes. Analysis of the inhibition kinetics revealed a mixed-type inhibitory effect on CYP1A1 supersome. The effects of the extract on BP-induced DNA damage and hepatic CYP activity in mice were also investigated. Micronuclei induction by BP and liver CYP1A1/2 activities significantly decreased in animals treated with the extract. The results suggest that Ulva fasciata aqueous-ethanolic extract inhibits BP bioactivation and it may be a potential chemopreventive agent.

  20. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    Science.gov (United States)

    Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

    2013-01-01

    Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

  1. Interaction of Vimang (Mangifera indica L. extract) with Fe(III) improves its antioxidant and cytoprotecting activity.

    Science.gov (United States)

    Pardo-Andreu, Gilberto L; Sánchez-Baldoquín, Carlos; Avila-González, Rizette; Yamamoto, Edgar T Suzuki; Revilla, Andrés; Uyemura, Sérgio Akira; Naal, Zeki; Delgado, René; Curti, Carlos

    2006-11-01

    A standard aqueous stem bark extract from selected species of Mangifera indica L. (Anacardiaceae)--Vimang, whose major polyphenolic component is mangiferin, displays potent in vitro and in vivo antioxidant activity. The present study provides evidence that the Vimang-Fe(III) mixture is more effective at scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, as well as in protecting against t-butyl hydroperoxide-induced mitochondrial lipid peroxidation and hypoxia/reoxygenation-induced hepatocytes injury, compared to Vimang alone. Voltammetric assays demonstrated that Vimang, in line with the high mangiferin content of the extract, behaves electrochemically like mangiferin, as well as interacts with Fe(III) in close similarity with mangiferin's interaction with the cation. These results justify the high efficiency of Vimang as an agent protecting from iron-induced oxidative damage. We propose Vimang as a potential therapy against the deleterious action of reactive oxygen species generated during iron-overload, such as that occurring in diseases like beta-thalassemia, Friedreich's ataxia and haemochromatosis.

  2. An Insight into Sargassum muticum Cytoprotective Mechanisms against Oxidative Stress on a Human Cell In Vitro Model

    Directory of Open Access Journals (Sweden)

    Susete Pinteus

    2017-11-01

    Full Text Available Sargassum muticum is a brown seaweed with strong potential to be used as a functional food ingredient, mainly due to its antioxidant properties. It is widely used in traditional oriental medicine for the treatment of numerous diseases. Nevertheless, few studies have been conducted to add scientific evidence on its effects as well as on the mechanisms of action involved. In this work, the human cell line MCF-7 was used as an in vitro cellular model to evaluate the capability of Sargassum muticum enriched fractions to protect cells on an oxidative stress condition. The concentration of the bioactive compounds was obtained by vacuum liquid chromatography applied on methanol (M and 1:1 methanol:dichloromethane (MD crude extracts, resulting in seven enriched fractions from the M extraction (MF2–MF8, and eight fractions from the MD extraction (MDF1–MDF8. All fractions were tested for cytotoxic properties on MCF-7 cells and the nontoxic ones were tested for their capacity to blunt the damaging effects of hydrogen peroxide-induced oxidative stress. The nontoxic effects were also confirmed in 3T3 fibroblast cells as a nontumor cell line. The antioxidant potential of each fraction, as well as changes in the cell’s real-time hydrogen peroxide production, in the mitochondrial membrane potential, and in Caspase-9 activity were evaluated. The results suggest that the protective effects evidenced by S. muticum can be related with the inhibition of hydrogen peroxide production and the inhibition of Caspase-9 activity.

  3. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells

    International Nuclear Information System (INIS)

    Sobhakumari, Arya; Schickling, Brandon M.; Love-Homan, Laurie; Raeburn, Ayanna; Fletcher, Elise V.M.; Case, Adam J.; Domann, Frederick E.; Miller, Francis J.

    2013-01-01

    Most head and neck squamous cell carcinomas (HNSCCs) overexpress epidermal growth factor receptor (EGFR) and EGFR inhibitors are routinely used in the treatment of HNSCC. However, many HNSCC tumors do not respond or become refractory to EGFR inhibitors. Autophagy, which is a stress-induced cellular self-degradation process, has been reported to reduce the efficacy of chemotherapy in various disease models. The purpose of this study is to determine if the efficacy of the EGFR inhibitor erlotinib is reduced by activation of autophagy via NOX4-mediated oxidative stress in HNSCC cells. Erlotinib induced the expression of the autophagy marker LC3B-II and autophagosome formation in FaDu and Cal-27 cells. Inhibition of autophagy by chloroquine and knockdown of autophagy pathway genes Beclin-1 and Atg5 sensitized both cell lines to erlotinib-induced cytotoxicity, suggesting that autophagy may serve as a protective mechanism. Treatment with catalase (CAT) and diphenylene iodonium (DPI) in the presence of erlotinib suppressed the increase in LC3B-II expression in FaDu and Cal-27 cells. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells. Knockdown of NOX4 using adenoviral siNOX4 partially suppressed erlotinib-induced LC3B-II expression, while overexpression of NOX4 increased expression of LC3B-II. These studies suggest that erlotinib may activate autophagy in HNSCC cells as a pro-survival mechanism, and NOX4 may play a role in mediating this effect. - Highlights: • Erlotinib increased LC3B-II and autophagosome formation in HNSCC cells. • Inhibition of autophagy sensitized HNSCC cells to erlotinib. • Erlotinib increased NOX4 promoter and 3′UTR luciferase activity. • Manipulating NOX4 decreases or increases autophagy

  4. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sobhakumari, Arya [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Schickling, Brandon M. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Love-Homan, Laurie; Raeburn, Ayanna [Department of Pathology, The University of Iowa, Iowa City, IA (United States); Fletcher, Elise V.M. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Case, Adam J. [Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Domann, Frederick E. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); Miller, Francis J. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); and others

    2013-11-01

    Most head and neck squamous cell carcinomas (HNSCCs) overexpress epidermal growth factor receptor (EGFR) and EGFR inhibitors are routinely used in the treatment of HNSCC. However, many HNSCC tumors do not respond or become refractory to EGFR inhibitors. Autophagy, which is a stress-induced cellular self-degradation process, has been reported to reduce the efficacy of chemotherapy in various disease models. The purpose of this study is to determine if the efficacy of the EGFR inhibitor erlotinib is reduced by activation of autophagy via NOX4-mediated oxidative stress in HNSCC cells. Erlotinib induced the expression of the autophagy marker LC3B-II and autophagosome formation in FaDu and Cal-27 cells. Inhibition of autophagy by chloroquine and knockdown of autophagy pathway genes Beclin-1 and Atg5 sensitized both cell lines to erlotinib-induced cytotoxicity, suggesting that autophagy may serve as a protective mechanism. Treatment with catalase (CAT) and diphenylene iodonium (DPI) in the presence of erlotinib suppressed the increase in LC3B-II expression in FaDu and Cal-27 cells. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells. Knockdown of NOX4 using adenoviral siNOX4 partially suppressed erlotinib-induced LC3B-II expression, while overexpression of NOX4 increased expression of LC3B-II. These studies suggest that erlotinib may activate autophagy in HNSCC cells as a pro-survival mechanism, and NOX4 may play a role in mediating this effect. - Highlights: • Erlotinib increased LC3B-II and autophagosome formation in HNSCC cells. • Inhibition of autophagy sensitized HNSCC cells to erlotinib. • Erlotinib increased NOX4 promoter and 3′UTR luciferase activity. • Manipulating NOX4 decreases or increases autophagy.

  5. Gas Chromatography-Mass Spectrometry Analysis of Ulva fasciata (Green Seaweed) Extract and Evaluation of Its Cytoprotective and Antigenotoxic Effects.

    Science.gov (United States)

    Rodeiro, Idania; Olguín, Sitlali; Santes, Rebeca; Herrera, José A; Pérez, Carlos L; Mangas, Raisa; Hernández, Yasnay; Fernández, Gisselle; Hernández, Ivones; Hernández-Ojeda, Sandra; Camacho-Carranza, Rafael; Valencia-Olvera, Ana; Espinosa-Aguirre, Jesús Javier

    2015-01-01

    The chemical composition and biological properties of Ulva fasciata aqueous-ethanolic extract were examined. Five components were identified in one fraction prepared from the extract by gas chromatography-mass spectrometry, and palmitic acid and its ethyl ester accounted for 76% of the total identified components. Furthermore, we assessed the extract's antioxidant properties by using the DPPH, ABTS, and lipid peroxidation assays and found that the extract had a moderate scavenging effect. In an experiment involving preexposition and coexposition of the extract (1-500 µg/mL) and benzo[a]pyrene (BP), the extract was found to be nontoxic to C9 cells in culture and to inhibit the cytotoxicity induced by BP. As BP is biotransformed by CYP1A and CYP2B subfamilies, we explored the possible interaction of the extract with these enzymes. The extract (25-50 µg/mL) inhibited CYP1A1 activity in rat liver microsomes. Analysis of the inhibition kinetics revealed a mixed-type inhibitory effect on CYP1A1 supersome. The effects of the extract on BP-induced DNA damage and hepatic CYP activity in mice were also investigated. Micronuclei induction by BP and liver CYP1A1/2 activities significantly decreased in animals treated with the extract. The results suggest that Ulva fasciata aqueous-ethanolic extract inhibits BP bioactivation and it may be a potential chemopreventive agent.

  6. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance.

    Science.gov (United States)

    Dupéré-Richer, D; Kinal, M; Ménasché, V; Nielsen, T H; Del Rincon, S; Pettersson, F; Miller, W H

    2013-02-07

    Histone deacetylase inhibitors (HDACi) have shown promising activity against hematological malignancies in clinical trials and have led to the approval of vorinostat for the treatment of cutaneous T-cell lymphoma. However, de novo or acquired resistance to HDACi therapy is inevitable, and their molecular mechanisms are still unclear. To gain insight into HDACi resistance, we developed vorinostat-resistant clones from the hematological cell lines U937 and SUDHL6. Although cross-resistant to some but not all HDACi, the resistant cell lines exhibit dramatically increased sensitivity toward chloroquine, an inhibitor of autophagy. Consistent with this, resistant cells growing in vorinostat show increased autophagy. Inhibition of autophagy in vorinostat-resistant U937 cells by knockdown of Beclin-1 or Lamp-2 (lysosome-associated membrane protein 2) restores sensitivity to vorinostat. Interestingly, autophagy is also activated in parental U937 cells by de novo treatment with vorinostat. However, in contrast to the resistant cells, inhibition of autophagy decreases sensitivity to vorinostat. These results indicate that autophagy can switch from a proapoptotic signal to a prosurvival function driving acquired resistance. Moreover, inducers of autophagy (such as mammalian target of rapamycin inhibitors) synergize with vorinostat to induce cell death in parental cells, whereas the resistant cells remain insensitive. These data highlight the complexity of the design of combination strategies using modulators of autophagy and HDACi for the treatment of hematological malignancies.

  7. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Chiong HS

    2013-03-01

    Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

  8. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus O.; Mortensen, Alicja; Nilas, Lisbeth

    2007-01-01

    Objectives: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. Study design: Thirty...... cholesterol was significantly higher at termination in the SoyLife(R) group (P lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or L-NAME or the endothelium...

  9. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation.

    Science.gov (United States)

    Hsieh, Chia-Jung; Kuo, Po-Lin; Hsu, Ying-Chan; Huang, Ya-Fang; Tsai, Eing-Mei; Hsu, Ya-Ling

    2014-02-01

    This study investigates the anticancer effect of arctigenin (ATG), a natural lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells. Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis in vitro and in vivo. ATG triggers the mitochondrial caspase-independent pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG nuclear translocation. ATG increased cellular reactive oxygen species (ROS) production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, significantly decreases ATG-mediated p38 activation and apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2 downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription factor activated by p38, and then upregulates histone H3K9 trimethylation in the Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together, the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of histone H3K9 trimethylation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  10. Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid, a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast Cells, and Rat Uterine Tissues.

    Science.gov (United States)

    Thongon, Natthakan; Boonmuen, Nittaya; Suksen, Kanoknetr; Wichit, Patsorn; Chairoungdua, Arthit; Tuchinda, Patoomratana; Suksamrarn, Apichart; Winuthayanon, Wipawee; Piyachaturawat, Pawinee

    2017-05-03

    Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.

  11. Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

    Science.gov (United States)

    Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

    2014-05-10

    This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. R & D of an Innovative Composite Scaffold Incorporated with Phytoestrogenic Icaritin for Treatment of Steroid-associated Osteonecrosis Lesion in Rabbits

    Science.gov (United States)

    Xie, Xinhui

    Bone defect is a common orthopaedic problem caused by many pathologic disorders such as tumor, trauma or metabolic diseases, including osteonecrosis (ON). ON is a disabling clinical condition characterized by the death of osteocytes, aggregation of marrow fat cells, a decrease in activity of bone marrow stem cells (BMSCs) pool, and degeneration of trabecular bone matrix, which affect more frequently young adults that usually leads to bone and articular cartilage destruction in joints, especially in hip and knee. High dose of steroid is one of the risk factors associated with ON, which sometimes is used for treatment of some medical conditions such as systemic lupus erythematosus (SLE), organ transplantation, asthma, rheumatologic arthritis (RA), and severe acute respiratory syndrome (SARS). Core decompression has been efficacious for treatment of early ON stages when the necrotic lesion is still small in size. However, ON lesion, weakens the cancellous bone within and adjacent to the necrotic region. Thus orthopaedic challenges in repair for steroid-associated ON lesion after core decompression may include the impaired osteogenic potential of stem-cell-pool under the influence of pulsed steroid and lack of platform for bone or/and neovascularization ingrowth after removal of large size necrotic bone. The proposed strategies for treatment of steroid-associated ON lesion are to provide biocompatible scaffold with required structure to fill the defect area after core decompression and osteogenic stimulator facilitating the repair of ON lesion. Previous works show that the PLGA (poly-lactic glycolic acid) and TCP (tricalcium phosphate) have good biocompatibility, osteoconduction and biodegradation to be used in bone defect repair, however no significant osteopromotive effects. Many endogenous factors are osteopromotive and also eventually osteoinductive, such as bone morphogenic proteins (BMPs). As an extraneous molecular, Icaritin, a small molecule derived from Epimedium -derived flavonoids (EF), is found to be able to facilitate matrix calcification, stimulate osteogenesis and inhibit adipogenesis of BMSCs. The present thesis work hypothesizes that the PLGA/TCP incorporating Icaritin to form a porous composite scaffold is osteopromotive and is able to enhance the repair of necrotic bone defect with steroid-associated ON after core decompression. The findings implied that the porous composite PLGA/TCP/Icaritin scaffold would be an appropriate osteopromotive scaffold implant or bone graft substitute biomaterial for potential application in skeletal tissue engineering. It was the first study to incorporate or homogenize the Chinese herbal molecule into the porous composite biomaterials for medical testing. Though the osteopromotive effect in ON model was observed in vivo, the molecular mechanism of osteogenesis remains for future investigations. (Abstract shortened by UMI.)

  13. Genistein, a Phytoestrogen in Soybean, Induces the Expression of Acetylcholinesterase via G Protein-Coupled Receptor 30 in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Etta Y. L. Liu

    2018-02-01

    Full Text Available Genistein, 4′,5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs, markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA-linked acetyl-cholinesterase (G4 AChE, a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA. The genistein-induced AChE expression was fully blocked by the pre-treatment of H89 (an inhibitor of protein kinase A, PKA and G15 (a selective G protein-coupled receptor 30 (GPR30 antagonist, which suggested a direct involvement of a membrane-bound estrogen receptor (ER, named as GPR30 in the cultures. In parallel, the estrogen-induced activation of GPR30 induced AChE expression in a dose-dependent manner. The genistein/estrogen-induced AChE expression was triggered by a cyclic AMP responding element (CRE located on the ACHE gene promoter. The binding of this CRE site by cAMP response element-binding protein (CREB induced ACHE gene transcription. In parallel, increased expression levels of miR132 and miR212 were found when cultured PC12 cells were treated with genistein or G1. Thus, a balance between production and destruction of AChE by the activation of GPR30 was reported here. We have shown for the first time that the activation of GPR30 could be one way for estrogen or flavonoids, possessing estrogenic properties, to enhance cholinergic functions in the brain, which could be a good candidate for possible treatment of neurodegenerative diseases.

  14. Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial

    Directory of Open Access Journals (Sweden)

    Larijani Bagher

    2005-10-01

    Full Text Available Abstract Background Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. Materials and methods This clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. Results Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p Conclusion In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.

  15. Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Mortensen, A; Nilas, Lisbeth

    2007-01-01

    -six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings...

  16. بررسی پراکسیداسیون چربیها و فعالیت آنزیمهای آنتی اکسیدانی در گویچه های سرخ زنان مبتلا به کم خونی فقر آهن Assessment of lipid peroxidation and activities of erythrocyte cytoprotective enzymes in women with iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Farshad Amirkhizi

    2008-10-01

    ای سرخ کاهش می یابد. پیامد کاهش فعالیت آنزیمهای آنتی اکسیدانی در انسان پیشرفت تخریب بافتی است که ممکن است زمینه ساز بروز بیماریهای دژنراتیو از جمله تصلب شرائین در آنها باشد.  

    • BACKGROUND: The aim of this study was to investigate whether the lipid peroxidation levels and activities of erythrocytecytoprotective enzymes can be affected by iron deficiency anemia (IDA in menstruating women.
    • METHODS: In this case-control study, 43 women with IDA, 43 women with iron deficiency (ID and 43 healthy controls were included. Lipid peroxidation levels were assessed by measuring the concentrations of plasma malondialdehyde (MDA (as byproduct of lipid peroxidation. We also evaluated the activities of erythrocyte cytoprotective enzymes by measuring activities of copper zinc-superoxide dismutase (CuZn-SOD, glutathione peroxidase (GPX and catalase (CAT in selected groups. Furthermore, total antioxidant capacity (TAC of  plasma was assessed for each subject.Comparisons between continuous variables across groups were performed by the calculation of one-way analysis of variance (ANOVA.
    • RESULTS: Mean plasma concentration of MDA was significantly higher in IDA group than that in ID group (3.49 ± 0.84 vs. 2.76 ± 0.59, ?mol/L, respectively, p < 0.01 and healthy group women (3.49 ± 0.84 vs. 2.94 ± 0.71 ?mol/L, respectively, p < 0.01. No significant difference was observed between ID and healthy groups in plasma MDA concentration (2.76 ± 0.59 vs. 2.94 ± 0.71, respectively. The mean erythrocyte CuZn-SOD activity in IDA group was significantly lower than that in healthy group women (674 ± 89 vs. 796 ± 82, respectively, p < 0.01. Furthermore, erythrocyte CAT activity was significantly lower in IDA group compared to both ID (162 ± 52 vs. 193 ± 72, respectively, p < 0

    • Prescription profile of Chinese herbal products containing coumestrol, genestein, and/or daidzein among female users: an analysis of national health insurance data in Taiwan between 1997 and 2007

      OpenAIRE

      Wu, Chien-Tung; Tzeng, Jeng-Nan; Lai, Jung-Nien; Tsan, Shun-Hua; Wang, Jung-Der

      2012-01-01

      Abstract Background Some Chinese herbs contain several kinds of phytoestrogens, and these herbs are commonly prescribed in Taiwan. Phytoestrogens may influence the effects of estrogen in females, although their activities are weak. This study aims to identify the risk and analyze the prescription profile of commonly used phytoestrogenic herbs in Taiwan. Methods The study analyzed women who had been prescribed phytoestrogenic herbs including coumestrol, genistein and/or daidzein between 1997 a...

    • Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities of Viola patrinii in Murine Hippocampal and Microglia Cells

      Directory of Open Access Journals (Sweden)

      Bin Li

      2012-01-01

      Full Text Available A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract of Viola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2 and cytokines (tumor necrosis factor-α and interleukin-1β. Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

    • Characterization of adult α- and β-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults.

      Directory of Open Access Journals (Sweden)

      Xiaolei Li

      Full Text Available OBJECTIVES: Hemoglobin (Hgb is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervical cancer were investigated. METHODOLOGY: The expression level of Hgb in cervical cancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR. We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervical cancer cells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS analysis and lactate dehydrogenase (LDH array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis. RESULTS: qRT-PCR analysis showed that Hgb-α- (HBA1 and Hgb-β-globin (HBB gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancer cells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1(H88R/HBB(H93R unable to bind hemo, suppressed oxidative stress and improved cell viability. CONCLUSIONS: The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervical cancer cells. These data provide a significant impact not only in globin biology but also in understanding of cervical cancer pathogenesis associated with oxidative stress.

    • Cytoprotection with amifostine in the simultaneous radio-chemotherapy of recurrent head and neck cancer; Zytoprotection mit Amifostin im Rahmen der Radiochemotherapie bei vorbestrahlten Kopf-Hals-Karzinomen

      Energy Technology Data Exchange (ETDEWEB)

      Buentzel, J.; Weinaug, R.; Kuettner, K. [Zentralklinikum gGmbH Suedthueringen, Suhl (Germany). Klinik fuer Hals-Nasen-Ohren-Heilkunde, Plastische Operationen; Glatzel, M.; Froehlich, D. [Zentralklinikum gGmbH Suedthueringen, Suhl (Germany). Klinik fuer Strahlentherapie; Schuth, J. [Essex Pharma, Muenchen (Germany)

      1999-11-01

      Purpose: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). Patients and methods: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20x1.5 Gy, Carboplatin 70 mg/m{sup 2} BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tomor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. Results: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation in 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: Side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: Mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. Conclusion: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region. (orig.) [German] Ziel: Bei einem Rezidiv- oder Zweitkarzinom im Kopf-Hals-Bereich sind die radiotherapeutischen Moeglichkeiten bei bereits vorbestrahlten Patienten sehr begrenzt. Inwieweit die Integration des selektiven Zytoprotektivums Amifostin in eine nochmalige Radiochemotherapie diese Situation aendert, ist Gegenstand der vorgelegten Analyse erster eigener Erfahrungen. Patienten und Methode: Zwischen 1995 und 1997 unterzogen wir 14 Patienten mit einem Rezidiv- oder Zweitkarzinom des HNO-Gebiets einer nochmaligen Radiochemotherapie (20mal, 1,5 Gy, Carboplatin 70 mg/m{sup 2} an Tag 1 bis 5 und 16 bis 20 der Bestrahlung, 500 mg Amifostin vor jeder Carboplatin-Infusion). 6/14 Patienten erhielten zur weiteren Dosisaufsaettigung eine zusaetzliche Brachytherapie (10 bis 15 Gy). Bei vier der 14 Patienten erfolgte die Radiochemotherapie nach chirurgischem Tumor-Debulking. Resultate: Wir erreichten mit der multimodalen Behandlung drei komplette (21,4%) and acht partielle Remissionen (57,1%). Bei einer medianen Beobachtungsdauer von 13 Monaten sind derzeit 3/14 Patienten verstorben. Haematologische Nebenwirkungen Grad 2 der WHO sahen wir bei einem Patienten. Akute nichthaematologische Nebenwirkungen waren: Mukositis Grad 0/1 bei sieben Patienten, Mukositis Grad 2 bei sieben Patienten, Dysphagie Grad 0/1 bei neun Patienten, Dysphagie Grad 2 bei fuenf Patienten, Xerostomie Grad 1 bei neun Patienten, Xerostomie Grad 2 bei drei Patienten. Einzige schwerwiegende Spaetnebenwirkung war bisher die Ausbildung einer submentalen Fistel im Pharynxtrichter eines laryngektomierten Patienten vier Monate nach Abschluss einer Brachytherapie. Schlussfolgerung: Diese ersten Ergebnisse deuten auf eine moegliche Erweiterung der Behandlungsmoeglichkeiten von Rezidivkarzinomen im Kopf-Hals-Gebiet hin, wenn das selektive Zytoprotektivum Amifostin in eine nochmalige Radiochemotherapie integriert wird. (orig.)

  1. Structure-Activity Relationships in the Cytoprotective Effect of Caffeic Acid Phenethyl Ester (CAPE) and Fluorinated Derivatives: Effects on Heme Oxygenase-1 Induction and Antioxidant Activities

    Science.gov (United States)

    2010-03-09

    Hishikawa, K., Nakaki, T., Fujita, T., 2005. Oral flavonoid supplementation attenuates atherosclerosis development in apolipoprotein E-deficient mice... flavonoids . Free Radical Biology & Medicine 20, 331–342. Wakabayashi, N., Dinkova-Kostova, A.T., Holtzclaw, W.D., Kang, M.I., Kobayashi, A., Yamamoto, M

  2. Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

    Science.gov (United States)

    Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

    2017-11-01

    Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

  3. Evaluation of the Cytoprotective and Antioxidant Activity of the Extracts of Eugenia Uniflora Lineau e Psidium Sobraleanum Proença & Landrum Against Heavy Metals

    Directory of Open Access Journals (Sweden)

    Celestina E. Sobral-Souza

    2014-09-01

    Full Text Available Objective: Evaluation of antioxidant activity has been an important issue considering its importance in human health. Recent studies show that the use of plants in the form of juices or teas as sources of natural antioxidants with low risk can be used as an aid to the treatment of various diseases. Material and Methods: Evaluation of the antioxidant potential in vitro, extracts of Eugenia uniflora and Psidium sobraleanum, as well as the quantification of phenols and flavonoids present in the extracts. Results: Findings showed a better antioxidant activity for the extract of Eugenia uniflora. In the TBARS test with egg phospholipids, extracts presented a reduction in the basal levels in the lipid peroxidation process; and when the Fe2 + extract was inducted, Psidium sobraleanum proved to be more efficient.. Conclusions: These tests proved that the extracts of leaves of the species Eugenia uniflora and Psidium sobraleanum present antioxidant activity which is directly related to phenolic substances produced in its secondary metabolism.

  4. On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

    OpenAIRE

    Zilka, Omkar; Shah, Ron; Li, Bo; Friedmann Angeli, Jos? Pedro; Griesser, Markus; Conrad, Marcus; Pratt, Derek A.

    2017-01-01

    Ferroptosis is a form of regulated necrosis associated with the iron-dependent accumulation of lipid hydroperoxides that may play a key role in the pathogenesis of degenerative diseases in which lipid peroxidation has been implicated. High-throughput screening efforts have identified ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent inhibitors of ferroptosis ? an activity that has been ascribed to their ability to slow the accumulation of lipid hydroperoxides. Herein we demonstrate t...

  5. On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death.

    Science.gov (United States)

    Zilka, Omkar; Shah, Ron; Li, Bo; Friedmann Angeli, José Pedro; Griesser, Markus; Conrad, Marcus; Pratt, Derek A

    2017-03-22

    Ferroptosis is a form of regulated necrosis associated with the iron-dependent accumulation of lipid hydroperoxides that may play a key role in the pathogenesis of degenerative diseases in which lipid peroxidation has been implicated. High-throughput screening efforts have identified ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent inhibitors of ferroptosis - an activity that has been ascribed to their ability to slow the accumulation of lipid hydroperoxides. Herein we demonstrate that this activity likely derives from their reactivity as radical-trapping antioxidants (RTAs) rather than their potency as inhibitors of lipoxygenases. Although inhibited autoxidations of styrene revealed that Fer-1 and Lip-1 react roughly 10-fold more slowly with peroxyl radicals than reactions of α-tocopherol (α-TOH), they were significantly more reactive than α-TOH in phosphatidylcholine lipid bilayers - consistent with the greater potency of Fer-1 and Lip-1 relative to α-TOH as inhibitors of ferroptosis. None of Fer-1, Lip-1, and α-TOH inhibited human 15-lipoxygenase-1 (15-LOX-1) overexpressed in HEK-293 cells when assayed at concentrations where they inhibited ferroptosis. These results stand in stark contrast to those obtained with a known 15-LOX-1 inhibitor (PD146176), which was able to inhibit the enzyme at concentrations where it was effective in inhibiting ferroptosis. Given the likelihood that Fer-1 and Lip-1 subvert ferroptosis by inhibiting lipid peroxidation as RTAs, we evaluated the antiferroptotic potential of 1,8-tetrahydronaphthyridinols (hereafter THNs): rationally designed radical-trapping antioxidants of unparalleled reactivity. We show for the first time that the inherent reactivity of the THNs translates to cell culture, where lipophilic THNs were similarly effective to Fer-1 and Lip-1 at subverting ferroptosis induced by either pharmacological or genetic inhibition of the hydroperoxide-detoxifying enzyme Gpx4 in mouse fibroblasts, and glutamate-induced death of mouse hippocampal cells. These results demonstrate that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process.

  6. Nitric oxide production by hemocytes of larva and pharate prepupa of Galleria mellonella in response to bacterial lipopolysaccharide: cytoprotective or cytotoxic?

    Czech Academy of Sciences Publication Activity Database

    Krishnan, Natraj; Hyršl, P.; Šimek, V.

    2006-01-01

    Roč. 142, 1-2 (2006), s. 103-110 ISSN 1532-0456 Institutional research plan: CEZ:AV0Z50070508 Keywords : nitric oxide * hemocytes * lipopolysaccharide Subject RIV: ED - Physiology Impact factor: 1.991, year: 2006

  7. Meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells

    Czech Academy of Sciences Publication Activity Database

    Linhartová, Irena; Basler, Marek; Ichikawa, J.; Pelicic, V.; Osička, Radim; Lory, S.; Nassif, X.; Šebo, Peter

    2006-01-01

    Roč. 263, - (2006), s. 109-118 ISSN 0378-1097 R&D Projects: GA ČR GA310/06/0720 Institutional research plan: CEZ:AV0Z50200510 Keywords : neisseria meningitidis * adherence * signaling Subject RIV: EE - Microbiology, Virology Impact factor: 2.068, year: 2006

  8. Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Tiange Li

    2017-01-01

    Full Text Available Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP on hydrogen peroxide (H2O2-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H2O2-induced intracellular reactive oxygen species (ROS generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1 expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2 nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK and extracellular signal-regulated protein kinase 1/2 (ERK1/2, which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.

  9. Exon-skipping strategy by ratio modulation between cytoprotective versus pro-apoptotic clusterin forms increased sensitivity of LNCaP to cell death.

    Directory of Open Access Journals (Sweden)

    Abdellatif Essabbani

    Full Text Available BACKGROUND: In prostate cancer the secreted form of clusterin (sCLU has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties. METHODOLOGY: In order to provide new therapeutic approaches targeting CLU, we developed a strategy based on exon skipping by using a lentiviral construct to preferentially induce the nuclear spliced form of the protein. The molecular construct was transduced in LNCaP cells for testing the modulation of sensitivity of the transduced cells to pro-apoptotic stress. RESULTS AND CONCLUSIONS: We showed an increase of nCLU/sCLU expression ratio in the prostate cancer cell line "LNCaP" after lentiviral vector-U7 nCLU transduction. Moreover, we showed a significant inhibition of cell proliferation in nCLU-U7 LNCaP cells after treatment with cisplatin and after exposure to ionizing radiation compared to control cells. Finally, we showed that nCLU-U7 LNCaP cells exposure to UV-C significantly reduced an increase of cell death compared to control. Finally, we showed that modulating nCLU expression had profound impact on Ku70/Bax interaction as well as Rad17 expression which could be a key mechanism in sensitizing cells to cell death. In conclusion, this is the first report showing that increasing of nCLU/sCLU expression ratio by using an "on demand alternative splicing" strategy successfully increased sensitivity to radiotherapy and chemotherapy of prostate cancer cells.

  10. The Effect of Hydro-alcoholic Extract of Leaves of Vitex on the Gestation Indices of Male Rats

    OpenAIRE

    Fereshteh Ramezanloo; Parvaneh Najafizadeh; Tahereh Naji; Gholamreza Amin; Zahra Mousavi; Gelareh Vahabzadeh

    2017-01-01

    Background: Phytoestrogens are some plant compounds with estrogenic biological effects which are found in many nutritional sources as soybean, flaxseed, and sesame. Vitex agnus-castus, also called Vitex, owns phytoestrogen properties. Studies have shown that phytoestrogens have different impacts on the gestation process and reproduction indices. Objective: The present study was aimed to investigate the effects of Vitex extract on the gestation indices in the male rat as well as studyin...

  11. Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus Aspergillus sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

    Directory of Open Access Journals (Sweden)

    Dong-Cheol Kim

    2016-04-01

    Full Text Available In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus Aspergillus sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2 in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK and phosphatidylinositol 3-kinase (PI3K/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.

  12. Antidiabetic effect of polyphenolic extracts from selected edible plants as α-amylase, α -glucosidase and PTP1B inhibitors, and β pancreatic cells cytoprotective agents - a comparative study.

    Science.gov (United States)

    Zakłos-Szyda, Małgorzata; Majewska, Iwona; Redzynia, Małgorzata; Koziołkiewicz, Maria

    2015-01-01

    Type 2 diabetes mellitus, which is usually a result of wrong dietary habits and reduced physical activity, represents 85-95% of all diabetes cases and among other diet related diseases is the major cause of deaths. The disease is characterized mainly by hyperglycemia, which is associated with attenuated insulin sensitivity or beta cells dysfunction caused by multiple stimuli, including oxidative stress and loss of insulin secretion. Since polyphenols possess multiple biological activities and constitute an important part of the human diet, they have recently emerged as critical phytochemicals in type 2 diabetes prevention and treatment. Their hypoglycemic action results from their antioxidative effect involved in recovering of altered antioxidant defenses and restoring insulin secreting machinery in pancreatic cells, or abilities to inhibit the activity of carbohydrates hydrolyzing enzymes (α-amylase and α-glucosidase) or protein tyrosine phosphatase 1B (PTP1B), which is known as the major negative regulator in insulin signaling. This study investigates the total phenolic content (Folin-Ciocalteu and HPLC methods) and antioxidant capacity (ABTS) of 20 polyphenolic extracts obtained from selected edible plants, which were screened in terms of α -amylase, α - glucosidase and protein tyrosine phosphatase 1B inhibitors or protective agents against oxidative stress induced by tertbutylhydroperoxide (t-BOOH) in βTC3 pancreatic beta cells used as a model target for antidiabetes drugs. The study concludes that Chaenomeles japonica, Oenothera paradoxa and Viburnum opulus may be promising natural sources for active compounds with antidiabetic properties.

  13. Prescription profile of Chinese herbal products containing coumestrol, genestein, and/or daidzein among female users: an analysis of national health insurance data in Taiwan between 1997 and 2007

    Directory of Open Access Journals (Sweden)

    Wu Chien-Tung

    2012-10-01

    Full Text Available Abstract Background Some Chinese herbs contain several kinds of phytoestrogens, and these herbs are commonly prescribed in Taiwan. Phytoestrogens may influence the effects of estrogen in females, although their activities are weak. This study aims to identify the risk and analyze the prescription profile of commonly used phytoestrogenic herbs in Taiwan. Methods The study analyzed women who had been prescribed phytoestrogenic herbs including coumestrol, genistein and/or daidzein between 1997 and 2007 in a fixed cohort taken from all female beneficiaries from the National Health Insurance Research Database of Taiwan. The prescription frequencies, cumulated dosages, and primary indications were listed. Results A total of 462,861 women were included in the study, of whom ~47.0% had used phytoestrogenic herbs at least once during the study period. A total of 6,270,813 prescriptions were recorded, and more than 20% of these contained phytoestrogens. The most commonly prescribed herb and formula were Puerariae Radix and Ge gen tang (Pueraria Decoction, respectively. Most of the prescriptions were issued for diseases of the respiratory system, followed by symptoms, signs, and ill-defined conditions and diseases of the musculoskeletal system and connective tissue. Conclusion This study shows that women who sought medical treatment from Chinese medicine doctors for relief of respiratory discomfort had a high possibility of exposure to phytoestrogenic herbs. Safety issues related to the female endocrine system should be a priority for future research.

  14. Prescription profile of Chinese herbal products containing coumestrol, genestein, and/or daidzein among female users: an analysis of national health insurance data in Taiwan between 1997 and 2007.

    Science.gov (United States)

    Wu, Chien-Tung; Tzeng, Jeng-Nan; Lai, Jung-Nien; Tsan, Shun-Hua; Wang, Jung-Der

    2012-10-16

    Some Chinese herbs contain several kinds of phytoestrogens, and these herbs are commonly prescribed in Taiwan. Phytoestrogens may influence the effects of estrogen in females, although their activities are weak. This study aims to identify the risk and analyze the prescription profile of commonly used phytoestrogenic herbs in Taiwan. The study analyzed women who had been prescribed phytoestrogenic herbs including coumestrol, genistein and/or daidzein between 1997 and 2007 in a fixed cohort taken from all female beneficiaries from the National Health Insurance Research Database of Taiwan. The prescription frequencies, cumulated dosages, and primary indications were listed. A total of 462,861 women were included in the study, of whom ~47.0% had used phytoestrogenic herbs at least once during the study period. A total of 6,270,813 prescriptions were recorded, and more than 20% of these contained phytoestrogens. The most commonly prescribed herb and formula were Puerariae Radix and Ge gen tang (Pueraria Decoction), respectively. Most of the prescriptions were issued for diseases of the respiratory system, followed by symptoms, signs, and ill-defined conditions and diseases of the musculoskeletal system and connective tissue. This study shows that women who sought medical treatment from Chinese medicine doctors for relief of respiratory discomfort had a high possibility of exposure to phytoestrogenic herbs. Safety issues related to the female endocrine system should be a priority for future research.

  15. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones.

    Science.gov (United States)

    Jarry, Hubertus; Spengler, Barbara; Porzel, Andrea; Schmidt, Juergen; Wuttke, Wolfgang; Christoffel, Volker

    2003-10-01

    Recent cell culture experiments indicated that extracts of Vitex agnus-castus (VAC) may contain yet unidentified phytoestrogens. Estrogenic actions are mediated via estrogen receptors (ER). To investigate whether VAC compounds bind to the currently known isoforms ERalpha or ERss, ligand binding assays (LBA) were performed. Subtype specific ER-LBA revealed a binding of VAC to ERss only. To isolate the ERss-selective compounds, the extract was fractionated by bio-guidance. The flavonoid apigenin was isolated and identified as the most active ERss-selective phytoestrogen in VAC. Other isolated compounds were vitexin and penduletin. These data demonstrate that the phytoestrogens in VAC are ERss-selective.

  16. SoyCaP: Soy and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Hamilton-Reeves, Jill M; Kurzer, Mindy S; Slaton, Joel

    2007-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  17. Lignan intake in the Netherlands and its relation with mortality

    NARCIS (Netherlands)

    Milder, I.E.J.

    2007-01-01

    KEYWORDS:lignans, phytoestrogens, secoisolariciresinol, liquid chromatography, mass spectrometry, food composition, intake, cancer, cardiovascular diseases, mortalityPlant lignans are diphenolic compounds that are present in many plant foods. The plant lignans

  18. Inhibitory activity of the isoflavone biochanin a on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation

    DEFF Research Database (Denmark)

    Hanski, Leena; Genina, Natalja; Uvell, Hanna

    2014-01-01

    Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump...

  19. Afican Health Sciences Vol 9 No 1.pmd

    African Journals Online (AJOL)

    Administrator

    2007-07-19

    Jul 19, 2007 ... in the management of cases of sterility/infertility in women. The present ..... Safety of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo ... phytoestrogens isolated from beer. Alcohol. Clin.

  20. Potential health benefits and problems associated with ...

    African Journals Online (AJOL)

    inhibitors, oligosaccharides and phytoestrogens in food legumes has both health ... of mixtures of these phytochemicals from food legumes, their interaction with ... potentials and utilization in foods and drugs which could be used as frontline ...

  1. Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol and pinoresinol in Dutch men and women

    NARCIS (Netherlands)

    Milder, I.E.J.; Feskens, E.J.M.; Arts, I.C.W.; Bueno de Mesquita, H.B.; Hollman, P.C.H.; Kromhout, D.

    2005-01-01

    Enterolignans (enterolactone and enterodiol) are phytoestrogens that are formed by the colonic microflora from plant lignans. They may reduce the risk of certain types of cancer and cardiovascular diseases. Initially, only secoisolariciresinol and matairesinol were considered to be enterolignan

  2. The safety and tolerance of phytotherapies in menopausal medicine – a review of the literature

    Directory of Open Access Journals (Sweden)

    Piotr Czuczwar

    2017-04-01

    Full Text Available Phytoestrogens are polyphenol, non-steroidal substances of plant origin, resembling 17-estradiol in structure. These substances can act as either agonists or antagonists of oestrogen receptors  and . Phytoestrogens are widely used to alleviate menopausal symptoms, such as hot flushes and night sweats. Most of the currently available products of plant origin registered to soften climacteric symptoms consist of extracts obtained from soy, red clover, or black cohosh. Non-hormonal phytotherapy is a new alternative for patients suffering from menopausal symptoms. Active ingredients such as PI 82-GC FEM extract do not show any direct hormonal mechanisms of action typical for oestrogens and phytoestrogens. There are concerns about the safety and tolerability of phytoestrogens. In this review we summarise the current literature regarding the clinical aspect of safety and tolerance of different phytotherapies used to relieve menopausal symptoms.

  3. Molecular screening of Chinese medicinal plants for progestogenic ...

    Indian Academy of Sciences (India)

    2014-05-01

    May 1, 2014 ... 2010). The risks of coronary heart diseases, breast cancer and pul- ... screened for phytoestrogen, but research and literature on the screening of ..... 2002 Risks and benefits of estrogen plus progestin in healthy postmeno-.

  4. SoyCaP: Soy and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Hamilton-Reeves, Jim M; Kurzer, Mindy S; Slaton, Joel

    2006-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  5. Effect of a Soy Dietary Supplement on Menopausal Symptoms and Hormones in Women at High Risk of Breast Cancer

    National Research Council Canada - National Science Library

    Woods, Margo

    1999-01-01

    The usefulness of a dietary soy supplement resulting in an intake of 45 mg/day of phytoestrogens, was tested in a randomized cross-over design in menopausal women aged 45-58 years of age who reported...

  6. Amelioration of Ischemia/Reperfusion Injury During Resuscitation from Hemorrhage by Induction of Heme Oxygenase-1 (HO-1) in a Conscious Mouse Model of Uncontrolled Hemorrhage

    Science.gov (United States)

    2013-10-01

    against menadione -induced-oxidative stress, also induces HIF1a and this may explain their cytoprotective effect. KEY RESEARCH ACCOMPLISHMENTS: Due to...August 2010 - October 2011 : Compared CDDO-lm, CAPE, CAPA induced H0-1 mediated cytoprotection against menadione -induced-oxidative stress in HUVEC cells...Pharmaceutical Scientists (AAPS) 2013: Comparison of atmospheric oxygen versus physiological levels on cytotoxicity of menadione and cytoprotection by

  7. Milk products and intestinal health

    NARCIS (Netherlands)

    Van der Meer, R; Bovee-Oudenhoven, IMJ; Sesink, ALA; Kleibeuker, JH

    Milk products may improve intestinal health by means of the cytoprotective effects of their high calcium phosphate (CaPi) content. We hypothesized that this cytoprotection may increase host defenses against bacterial infections as well as decrease colon cancer risk. This paper summarizes our studies

  8. Amang et al., Afr J Tradit Complement Altern Med. (2014) 11(1):165 ...

    African Journals Online (AJOL)

    cadewumi

    Materials and Methods: In this study, we tested the cytoprotective potential of the ... In the present experiment, various animal models of gastric ulcer were used to test the ..... Ionization: Reactivity relationships for cysteine thiols in polypeptides.

  9. Does autophagy have a license to kill mammalian cells?

    NARCIS (Netherlands)

    Scarlatti, F.; Granata, R.; Meijer, A. J.; Codogno, P.

    2009-01-01

    Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the

  10. Mesna

    Science.gov (United States)

    ... class of medications called cytoprotectants. It works by protecting the bladder against some of the harmful effects ... such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child- ...

  11. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    Directory of Open Access Journals (Sweden)

    Tonguç Utku Yilmaz

    2015-01-01

    Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic/normal conditions.

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 316 ... Vol 11 (2007), Evaluation Of Antimitotic And Anticancer Activity Of ... CYTOPROTECTIVE EFFECTS OF CISSUS QUADRANGULARIS L. VARIAN II IN RATS. ... Vol 11 (2007), Hepatoprotective Action Of Cordia dichotoma ...

  13. Identification of exposure to environmental chemicals in children and older adults using human biomonitoring data sorted by age

    DEFF Research Database (Denmark)

    Choi, Judy; Knudsen, Lisbeth E.; Mizrak, Seher

    2017-01-01

    /classes of chemicals with potentially higher body burden in children or older adults. Children appear to have higher body burden of bisphenol A (BPA), some phytoestrogens, perchlorate, and some metabolites of polycyclic aromatic hydrocarbons and benzene. On the other hand, older adults appear to have higher body...

  14. Lack of ABCG2 shortens latency of BRCA1-deficient mammary tumors and this is not affected by genistein or resveratrol

    NARCIS (Netherlands)

    Zander, Serge A. L.; Kersbergen, Ariena; Sol, Wendy; Gonggrijp, Maaike; van de Wetering, Koen; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

    2012-01-01

    In addition to their role in drug resistance, the ATP-binding cassette (ABC) transporters ABCG2 and ABCB1 have been suggested to protect cells from a broad range of substances that may foster tumorigenesis. Phytoestrogens or their metabolites are substrates of these transporters and the influence of

  15. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

    Science.gov (United States)

    Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

    2010-09-01

    The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications. Copyright 2010 John Wiley & Sons, Ltd.

  16. Glycinol Enhances Osteogenic Differentiation and Attenuates the Effects of Aging on Bone Marrow-derived Mesenchymal Stem Cells

    Science.gov (United States)

    Osteoporosis is characterized by decreased bone mineral density and increased risk of fractures. It is most prevalent in the elderly population, leading to significant morbidity and mortality. Recently, phytoestrogens have gained significant attention as an alternative therapy due to their structura...

  17. 第一节 Morris水迷宫实验

    African Journals Online (AJOL)

    lenovo

    After the individual treatments for 8 weeks ended, the serum levels of estradiol ... Transcutaneous electrical acupoint stimulation (TEAS) is an innovative and .... awareness of HRT was poor, which was influenced by menopausal, working and ... Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and.

  18. Genistein genotoxicity: Critical considerations of in vitro exposure dose

    International Nuclear Information System (INIS)

    Klein, Catherine B.; King, Audrey A.

    2007-01-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 μM as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein

  19. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Sotoca, A.M.; Vervoort, J.; Louisse, J.

    2013-01-01

    Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic

  20. African Journal of Biotechnology - Vol 11, No 50 (2012)

    African Journals Online (AJOL)

    Phytoestrogenic property of Labisia pumila for use as an estrogen replacement therapy agent · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Poh Su Wei Melissa, Visneswaran Navaratnam, Chia Yoke Yin, 11053-11056. http://dx.doi.org/10.5897/AJB12.160 ...

  1. Mechanism of Action of a Novel Analog of Vitamin D3, 1alpha-hydroxy-24-ethyl Cholecalciferol (D5), in Normal and Transformed Human Breast Epithelial Cells

    Science.gov (United States)

    2003-05-01

    retinoids, deltanoids (vitamin D derivatives), phytoestrogens, flavonoids , and aromatase inhibitors among others (Kelloffet al, 1996). On a global basis...Dietetics, University of Illinois at Chicago, Chicago. Responsibilities included development and validation of MDA-TBA assay by HPLC with fluorometric

  2. Rapid dereplication of estrogenic compounds in pomegranate (Punica granatum) using on-line biochemical detection coupled to mass spectrometry

    NARCIS (Netherlands)

    van Elswijk, D.A.; Schobel, U.; Lansky, EP; Irth, H.; de Greef, J

    2004-01-01

    During recent years, phytoestrogens have been receiving an increasing amount of interest, as several lines of evidence suggest a possible role in preventing a range of diseases, including the hormonally dependent cancers. In this context, various parts of the pomegranate fruit (Punica granatum;

  3. Monoclonal antibody-based time-resolved fluorescence immunoassays for daidzein, genistein and equol in blood and urine

    DEFF Research Database (Denmark)

    Talbot, Duncan C.S.; Ogborne, Richard M.; Dadd, Tony

    2007-01-01

    Background: Time-resolved fluorescence immunoessays (TR-FIAs) for phytoestrogens in biological samples are an alternative to mass spectrometric methods. These immunoessays were used to test urne and plasma samples from individuals in a dietary trial aimed at determining the efficacy of dietary is...

  4. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    International Nuclear Information System (INIS)

    Aguilar, David; Strom, Joshua; Chen, Qin M.

    2014-01-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA

  5. Estrogenic plant foods of red colobus monkeys and mountain gorillas in Uganda.

    Science.gov (United States)

    Wasserman, Michael D; Taylor-Gutt, Alexandra; Rothman, Jessica M; Chapman, Colin A; Milton, Katharine; Leitman, Dale C

    2012-05-01

    Phytoestrogens, or naturally occurring estrogen-mimicking compounds, are found in many human plant foods, such as soybeans (Glycine max) and other legumes. Because the consumption of phytoestrogens may result in both health benefits of protecting against estrogen-dependent cancers and reproductive costs of disrupting the developing endocrine system, considerable biomedical research has been focused on the physiological and behavioral effects of these compounds. Despite this interest, little is known about the occurrence of phytoestrogens in the diets of wild primates, nor their likely evolutionary importance. We investigated the prevalence of estrogenic plant foods in the diets of two folivorous primate species, the red colobus monkey (Procolobus rufomitratus) of Kibale National Park and mountain gorilla (Gorilla beringei) of Bwindi Impenetrable National Park, both in Uganda. To examine plant foods for estrogenic activity, we screened 44 plant items (species and part) comprising 78.4% of the diet of red colobus monkeys and 53 plant items comprising 85.2% of the diet of mountain gorillas using transient transfection assays. At least 10.6% of the red colobus diet and 8.8% of the gorilla diet had estrogenic activity. This was mainly the result of the red colobus eating three estrogenic staple foods and the gorillas eating one estrogenic staple food. All estrogenic plants exhibited estrogen receptor (ER) subtype selectivity, as their phytoestrogens activated ERβ, but not ERα. These results demonstrate that estrogenic plant foods are routinely consumed by two folivorous primate species. Phytoestrogens in the wild plant foods of these two species and many other wild primates may have important implications for understanding primate reproductive ecology. Copyright © 2012 Wiley Periodicals, Inc.

  6. Prostate cancer: The main risk and protective factors-Epigenetic modifications.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2015-02-01

    With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Suppression of T cell-induced osteoclast formation

    Energy Technology Data Exchange (ETDEWEB)

    Karieb, Sahar; Fox, Simon W., E-mail: Simon.fox@plymouth.ac.uk

    2013-07-12

    Highlights: •Genistein and coumestrol prevent activated T cell induced osteoclast formation. •Anti-TNF neutralising antibodies prevent the pro-osteoclastic effect of activated T cells. •Phytoestrogens inhibit T cell derived TNF alpha and inflammatory cytokine production. •Phytoestrogens have a broader range of anti-osteoclastic actions than other anti-resorptives. -- Abstract: Inhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10{sup −7} M) previously shown to directly inhibit osteoclast formation also suppressed the formation of TRAP positive osteoclast induced by con A activated T cells, which was dependent on inhibition of T cell derived TNF-α. While both reduced osteoclast formation their mechanism of action differed. The anti-osteoclastic effect of coumestrol was associated with a dual effect on con A induced T cell proliferation and activation; 10{sup −7} M coumestrol significantly reducing T cell number (0.36) and TNF-α (0.47), IL-1β (0.23) and IL-6 (0.35) expression, whereas genistein (10{sup −7} M) had no effect on T cell number but a more pronounced effect on T cell differentiation reducing expression of TNF-α (0.49), IL-1β (0.52), IL-6 (0.71) and RANKL (0.71). Phytoestrogens therefore prevent the pro-osteoclastic action of T cells suggesting they may have a role in the control of inflammatory bone loss.

  8. Inhibition of galactosamine cytotoxicity in an in vivo/in vitro hepatocellular toxicity model

    International Nuclear Information System (INIS)

    MacDonald, J.R.; Thayer, K.J.; White, C.

    1987-01-01

    A combined in vivo/in vitro model of galactosamine hepatotoxicity was employed to test whether previously reported cytoprotective actions of cystamine administration on galactosamine-induced hepatic injury in vivo could be attributed to a direct action of cystamine on toxicant-challenged hepatocytes. In this model, male Sprague-Dawley rats received a 400 mg/kg galactosamine challenge via intraperitoneal injection 1 hr prior to portal vein cannulation for hepatocyte isolation. Isolated cells are established in monolayer culture and galactosamine-induced cellular injury is then expressed over the ensuing 24-48 hr in culture. Consistent with the biochemical basis of galactosamine-induced hepatocellular injury in vivo, cytotoxicity could be prevented by in vitro uridine treatments within 3 hr of the in vivo galactosamine challenge, but not when added 12 hr later. Cystamine, in contrast, exhibited a cytoprotective effect even when added to cultures 12 hr after the in vivo toxicant challenge. Post-toxicant cytoprotection by cystamine in vitro was concentration dependent and did not produce an alteration of hepatocyte nonprotein sulfhydryl content. Post-toxicant cytoprotection by uridine and cystamine in this in vivo/in vitro model of toxicity were fully consistent with in vivo protection from galactosamine-induced necrosis by these agents. This model eliminates potential extrahepatic mechanisms for cystamine's hepatoprotective effect and demonstrates a direct cytoprotective action on galactosamine-challenged hepatocytes

  9. The influence of bovine milk high or low in isoflavones on hepatic gene expression in mice

    DEFF Research Database (Denmark)

    Skaanild, Mette Tingleff; Nielsen, Tina Skau

    2012-01-01

    Isoflavones have generated much attention due to their potential positive effects in various diseases. Phytoestrogens especially equol can be found in bovine milk, as feed ration for dairy cows is comprised of plants containing phytoestrogens. The aim of this study was to analyze the changes...... in hepatic gene expression after dietary intake of milk high and low in isoflavones. In addition to pelleted feed female NMRI mice were offered water, water added either 17β-estradiol, equol, Tween 80, and milk high and low in isoflavone content for a week. Gene expression was analyzed using an array q......PCR kit. It was revealed that Tween 80 and 17β-estradiol upregulated both phase I and phase II genes to the same extent whereas equol alone, high and low isoflavone milk did not alter the expression of phase I genes but decreased the expression of phase II genes. This study shows that dietary isoflavones...

  10. Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

    Directory of Open Access Journals (Sweden)

    Masao Hattori

    2013-01-01

    Full Text Available Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−-arctigenin, the aglycone of arctiin, was demethylated to (−-dihydroxyenterolactone (DHENL by Eubacterium (E. sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (−-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (−-arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R-2-(4-hydroxy-3-methoxybenzyl-3-(3,4-dihydroxybenzyl-butyrolactone was 7.9 × 10−4 M.

  11. Prevalence and predictors of complementary and alternative medicine/non-pharmacological interventions use for menopausal symptoms within the UK Collaborative Trial of Ovarian Cancer Screening

    DEFF Research Database (Denmark)

    Gentry-Maharaj, A; Karpinskyj, C; Glazer, C

    2017-01-01

    OBJECTIVES: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) and non-pharmacological interventions (NPI) for menopausal symptom relief. We report on the prevalence and predictors of CAM/NPI among UK postmenopau......OBJECTIVES: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) and non-pharmacological interventions (NPI) for menopausal symptom relief. We report on the prevalence and predictors of CAM/NPI among UK...... for herbal therapies (43.8%; 9725/22 206), vitamins (42.6%; 9458/22 206), lifestyle approaches (32.1%; 7137/22 206) and phytoestrogens (21.6%; 4802/22 206). Older women reported less ever-use of herbal therapies, vitamins and phytoestrogens. Lifestyle approaches, aromatherapy...

  12. Estrogenic activity of constituents from the rhizomes of Rheum undulatum Linné.

    Science.gov (United States)

    Park, SeonJu; Kim, Yun Na; Kwak, Hee Jae; Jeong, Eun Ju; Kim, Seung Hyun

    2018-02-15

    Stilbenes have been reported to be phytoestrogen compounds owing to its structural similarity to the estrogenic agent diethylstilbestrol. To find new stilbene-derivative phytoestrogens, isolation of stilbene-rich R. undulatum was performed and led to identify six new compounds (1-5 and 28), one newly determined absolute configurations compound (27) together with 21 previously reported compounds (6-26). The structures of compounds were determined on the basis of extensive spectroscopic methods including 1D and 2D NMR and CD spectra data. All the isolated compounds were tested for their estrogenic activities in HepG2 cells transiently transfected with ERα, ERβ and ERE-reporter plasmid. Among them, stilbene-derivatives, piceatannol 3'-O-β-d-xylopyranoside (12), cis-rhaponticin (16) and rhapontigenin 3'-O-β-d-glucopyranoside (17), showed the more potent binding affinity for estrogen receptors than 17β-estrodiol. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

    OpenAIRE

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-01-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured s...

  14. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2012-03-01

    Manuscript s • Submitted to the Journal of Nutritional Biochemistry (Feb 21, 2012) “The soy isoflavone equol may increase cancer malignancy via upregulation...29] Ko KP, Park SK, Park B et al. Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean...Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression. PRINCIPAL INVESTIGATOR: Columba de la Parra Simental CONTRACTING

  15. Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats

    OpenAIRE

    Mohammad Allahtavakoli; Najmeh Honari; Iran Pourabolli; Mohammad Kazemi Arababadi; Hossein Ghafarian; Ali Roohbakhsh; Ali Esmaeili Nadimi; Ali Shamsizadeh

    2015-01-01

    Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. Methods: 24 female Wistar rats weighing 180?220 g were used in this study. The animals w...

  16. Effects of " vitex agnus castus" extract and magnesium supplementation, alone and in combination, on osteogenic and angiogenic factors and fracture healing in women with long bone fracture

    OpenAIRE

    Mohammad Hassan Eftekhari; Zahra Hassanzadeh Rostami; Mohammad Jafar Emami; Hamid Reza Tabatabaee

    2014-01-01

    Background: The purpose of this study was to investigate the effects of the combination of vitex agnus castus extract, as a source of phytoestrogens, plus magnesium supplementation on osteogenic and angiogenic factors and callus formation in women with long bone fracture. Material and Methods: In a double-blind randomized placebo controlled trial, 64 women with long bone fracture, 20-45 years old, were randomly allocated to receive 1) one Agnugol tablet (4 mg dried fruit extract of vitex agnu...

  17. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    Science.gov (United States)

    2008-05-01

    Dietary flavonoid intake and breast cancer survival among women on Long Island. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2285-92...Kuklenyik, Z., Needham, L.L., Calafat, A.M., 2005. Automated on-line column-switching HPLC -MS/MS method with peak focusing for the determination of...action. Environ Health Perspect 110:917–921. Rybak ME, Parker DL, Pfeiffer CM. 2006. Determination of Urinary Phytoestrogens by HPLC -MS/MS: A Comparison

  18. Prevention of Post-Radiotherapy Failure in Prostate Cancer by Vitamin D

    Science.gov (United States)

    2003-03-01

    retinoids, deltanoids (vitamin D deriva- tives), phytoestrogens, flavonoids , and aromatase inhibitors, among others (Kelloffet al. 1996). On a global...immunolinked) 570.9 ng D5. IMC was ( HPLC ) analysis. The control diet was mixed with ethanol (equal further diluted with HBSS to get a final injection...for the purity of the substance is 95-100%, and the analytical method used to assure the identity and purity of the compound is reversed-phase HPLC

  19. Soy-based Infant Formula: A Safe Choice for Babies?

    OpenAIRE

    Su, Tien-l Karleen

    2002-01-01

    Making up about 25% of the current infant-formula market in the U.S., soy-based infant formulas are lifesaving alternatives for infants who cannot rely on traditional sources of milk for complete nutrition. While many studies have supported the effectiveness of soy-formula consumption for normal growth and development, the controversy over the potentially harmful effects of early exposure to isoflavones (phytoestrogens found in soy formulas) remains to be resolved. The plasma concentration of...

  20. Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ER?

    OpenAIRE

    Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

    2017-01-01

    Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of m...

  1. Blackcurrant Anthocyanins Increase the Levels of Collagen, Elastin, and Hyaluronic Acid in Human Skin Fibroblasts and Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Naoki Nanashima

    2018-04-01

    Full Text Available Blackcurrants (Ribes nigrum L. contain high levels of anthocyanin polyphenols, which have beneficial effects on health, owing to their antioxidant and anticarcinogenic properties. Phytoestrogens are plant-derived substances with estrogenic activity, which could have beneficial effects on the skin. Estradiol secretion decreases during menopause, reducing extracellular matrix (ECM component production by skin fibroblasts. Using a normal human female skin fibroblast cell line (TIG113 and ovariectomized rats, the present study investigated whether an anthocyanin-rich blackcurrant extract (BCE and four blackcurrant anthocyanins have novel phytoestrogenic activities that could benefit the skin in menopausal women. In TIG113 cells, a microarray and the Ingenuity® Pathway Analysis showed that 1.0 μg/mL of BCE upregulated the expression of many estrogen signaling-related genes. A quantitative RT-PCR analysis confirmed that BCE (1.0 or 10.0 μg/mL and four types of anthocyanins (10 μM altered the mRNA expression of ECM proteins and enzymes involved in ECM turnover. Immunofluorescence staining indicated that the anthocyanins stimulated the expression of ECM proteins, such as collagen (types I and III and elastin. Dietary administration of 3% BCE to ovariectomized rats for 3 months increased skin levels of collagen, elastin, and hyaluronic acid. This is the first study to show that blackcurrant phytoestrogens have beneficial effects on skin experimental models.

  2. 8-Alkylcoumarins from the Fruits of Cnidium monnieri Protect against Hydrogen Peroxide Induced Oxidative Stress Damage

    Directory of Open Access Journals (Sweden)

    Chi-I Chang

    2014-03-01

    Full Text Available Three new 8-alkylcoumarins, 7-O-methylphellodenol-B (1, 7-methoxy-8-(3-methyl- 2,3-epoxy-1-oxobutylchromen-2-one (2, and 3'-O-methylvaginol (3, together with seven known compounds (4–10 were isolated from the fruits of Cnidium monnieri. Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. All the isolates were evaluated the cytoprotective activity by MTS cell proliferation assay and the results showed that all the three new 8-alkylcoumarins exhibited cytoprotective effect on Neuro-2a neuroblastoma cells injured by hydrogen peroxide.

  3. Synthesis of Reactive Polymers for Acrolein Capture Using AGET ATRP.

    Science.gov (United States)

    Beringer, Laura T; Li, Shaohua; Gilmore, Gary; Lister, John; Averick, Saadyah

    2015-10-05

    Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.

  4. Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats.

    Science.gov (United States)

    Itoh, Y H; Noguchi, R

    2000-01-01

    The purpose of this study was to assess the preventive effect of pre-mild whole-body heating (WBH) on gastric ulcer induced by restraint and water-immersion stress. The ulcer index and ulcer area ratio in rats exposed to restraint and water-immersion stress were significantly decreased (p immersion stress alone (p immersion, thereby preventing gastric ulcer formation. Pre-treatment with mild WBH is the safest cytoprotective method through the accumulation of HSP 70f. The concentration of HSP 70f in peripheral lymphocytes may be a useful clinical laboratory indicator for assessing the level of HSP 70f as having cytoprotective activity.

  5. NTP-CERHR monograph on Soy Infant Formula.

    Science.gov (United States)

    2010-09-01

    Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones ("phytoestrogens") that occur naturally in some legumes, especially soybeans. Phytoestrogens are non-steroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for evaluation by the National Toxicology Program (NTP) because of the: (1)availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as a number of studies on human infants fed soy infant formula, (2)the availability of information on exposures in infants fed soy infant formula, and (3)public concern for effects on infant or child development. The NTP evaluation was conducted through its Center for the Evaluation of Risks to Human Reproduction (CERHR) and completed in September 2010. The results of this soy infant formula evaluation are published in an NTP Monograph. This document contains the NTP Brief on Soy Infant Formula, which presents NTP's opinion on the potential for exposure to soy infant formula to cause adverse developmental effects in humans. The NTP Monograph also contains an expert panel report prepared to assist the NTP in reaching conclusions on soy infant formula. The NTP concluded there is minimal concern for adverse effects on development in infants who consume soy infant formula. This level of concern represents a "2" on the five-level scale of concern used by the NTP that ranges from negligible concern ("1") to serious concern ("5"). This

  6. Redox Modulation by Amaranth Oil in Human Lung Fibroblasts

    NARCIS (Netherlands)

    Semen, K.O.; den Hartog, G.J.M.; Kaminsky, D.V.; Sirota, T.V.; Maij, N.G.A.A.; Yelisyeyeva, O.P.; Bast, A.

    2013-01-01

    Amaranth oil has several health benefits. It has lipid lowering, anti-diabetic, immune modulatory and cytoprotective properties, activates the function of mitochondria and improves heart rate variability. It has been suggested that the effect of amaranth oil on redox status is involved in this

  7. Download this PDF file

    African Journals Online (AJOL)

    acer

    Figure 3 portraits the histopathological changes in a cerebral section of pups ..... against gastric injury induced by ethanol and indomethacin in rodents. .... Cytoprotective effect of mangiferin on benzo(a)pyreneinduced lung ... Prenatal Curcumin Administration Reverses Behavioral and Neurochemical Effects and Decreases.

  8. Mononuclear nonheme iron(III) complexes that show superoxide dismutase-like activity and antioxidant effects against menadione-mediated oxidative stress.

    Science.gov (United States)

    Hitomi, Yutaka; Iwamoto, Yuji; Kashida, Akihiro; Kodera, Masahito

    2015-05-21

    This communication describes the superoxide dismutase (SOD)-like activity of mononuclear iron(III) complexes with pentadentate monocarboxylamido ligands. The SOD activity can be controlled by the electronic nature of the substituent group on the ligand. The nitro-substituted complex showed clear cytoprotective activity against menadione-mediated oxidative stress in cultured cells.

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 263 ... Vol 5, No 2 (2006), Blood glucose level and lipid profile in rats fed on Treculia Africana (Breadfruit) diet: A sub-chronic study, Abstract. OO Okwari, OE Ofem, ... Vol 9, No 2 (2010), Comparative Effect of Fresh, Thermoxidized and Irradiated Oil on Gastric Acid Secretion and Cytoprotection in Rats, Abstract.

  10. Effects of a heat shock protein inducer on the atrial fibrillation substrate caused by acute atrial ischaemia

    NARCIS (Netherlands)

    Sakabe, Masao; Shiroshita-Takeshita, Akiko; Maguy, Ange; Brundel, Bianca J. J. M.; Fujiki, Akira; Inoue, Hiroshi; Nattel, Stanley

    2008-01-01

    Aims Heat shock proteins (HSPs) are a set of endogenous cytoprotective factors activated by various pathological conditions. This study addressed the effects of geranylgeranylacetone (GGA), an orally active HSP inducer, on the atrial fibrillation (AF) substrate associated with acute atria( ischaemia

  11. Protective Effects of Tetrahydrocurcumin and Curcumin against ...

    African Journals Online (AJOL)

    Purpose: To investigate the cytoprotective effect of tetrahydrocurcumin, (THC) and curcumin (CUR) on cytotoxicity induced by doxorubicin and cadmium in Chang liver cells. Methods: Cytotoxicity was determined by sulforhodamine B assay. The expression of nuclear factorerythroid- 2-related factor 2 (Nrf2) Nrf2 regulated ...

  12. Gastroprotective effects of leaf extracts of Carpolobia lutea ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-05

    Jan 5, 2009 ... INTRODUCTION. Carpolobia lutea G.Don (family: polygalaceae) occurred .... nary profile of antiulcer effects of C. lutea leaf (Andreo et al., 2006). The antiulcer assays ..... (John and Onabanjo, 1990; Nwafor et al., 1996). Flav- onoids have ... Cytoprotection (Robert et al., 1979) in rats as evidenced by the ...

  13. BKR 27(1) pp. 50-55 (Achuba et al)

    African Journals Online (AJOL)

    Femi J. Olorunniji

    2015-03-31

    Mar 31, 2015 ... Biokemistri 27(1): 50–55. 54. Farombi, E.O. (2000) Mechanisms for the hepatoprotective action of kolaviron, studies on hepatic enzymes, microsomal lipids and peroxidation in carbon tetrachloride-treated rats. Pharmacological Research 42: 75–80. Farris MW (1991) Cadmium toxicity: Unique cytoprotective.

  14. Clinical efficacy of sucralfate in reflux esophagitis. Comparison with cimetidine

    NARCIS (Netherlands)

    Tytgat, G. N.

    1987-01-01

    Sucralfate has been evaluated in reflux esophagitis, based on its protective adherence to denuded surfaces, its bile salt-binding properties, and its cytoprotective properties. Histamine (H2)-receptor blockers are currently considered the standard therapy. The goal of this study was to compare the

  15. Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination.

    Science.gov (United States)

    Alkholifi, Faisal K; Albers, David S

    2015-10-05

    There is accumulating evidence that supports the involvement of reactive oxygen species (ROS), mitochondrial dysfunction and inflammation in the pathogenesis of neurodegenerative diseases. Thus, it is plausible that a multi-targeted therapeutic approach may be a more effective strategy to retard or even potentially halt the progression of the disease. Taurine is an organic acid that has a role in the regulation of oxidative stress and promoting mitochondrial normal functions, and N-Acetyl cysteine (NAC) is a well-known anti-oxidant and glutathione precursor. The main purpose of this study was to examine the cytoprotective effects of taurine alone or in combination with NAC against rotenone-induced toxicity in the SH-SY5Y neuroblastoma cell line. Taurine treatment produced a concentration-dependent reduction in rotenone-induced cell death. From this, we tested sub-effective concentrations of taurine in combination with low, sub-effective concentrations of NAC against rotenone toxicity, and found the combined treatment afforded greater cytoprotection than either treatment alone. The combined taurine/NAC treatment also attenuated rotenone-induced reductions in aconitase activity suggesting the cytoprotection afforded by the combined treatment may be associated with anti-oxidative mechanisms. Together, our data suggest that a multi-targeted approach may yield new avenues of research exploring the utility of combining therapeutic agents with different mechanisms of actions at concentrations lower than previously tested and shown to be cytoprotective. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Author Details

    African Journals Online (AJOL)

    Simoyi, Reuben H. Vol 55 (2002) - Articles Complex Kinetics in the Reaction of Taurine with Aqueous Bromine and Acidic Bromate : A Possible Cytoprotective Role against Hypobromous Acid Abstract PDF. ISSN: 0379-4350. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  17. Author Details

    African Journals Online (AJOL)

    Effects of tahitian noni (Morinda citrifolia L.) juice on some hematological and biochemical parameters of male albino wistar rats. Abstract · Vol 26, No 1 (2011) - Articles The relationship between body mass index, semen and sex hormones in adult male. Abstract PDF · Vol 26, No 1 (2011) - Articles Gastric Cytoprotection and ...

  18. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

    Directory of Open Access Journals (Sweden)

    Bikul Das

    2008-10-01

    Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

  19. Ventilator-associated pneumonia in critically ill African patients on ...

    African Journals Online (AJOL)

    Background: Stress ulcer prophylaxis is an integral part of the care of the critically ill. Agents that alter gastric pH may predispose these patients to gastric colonisation, with subsequent pneumonia and/or sepsis. Cytoprotective agents such as sucralfate preserve gastric acidity and may be protective. Objective: To determine ...

  20. Protective Role of Commiphora molmol Extract against Liver and ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research January 2016; 15 (1): 65-72 ... aminotransferase (AST), total bilirubin, urea, creatinine, cholesterol and triglycerides showed a ... rabbits and Giardia lamblia infection in rats [11]. ... [12], antigastric ulcer and cytoprotective effects ... temperature and humidity, fed with commercial.

  1. Lamium album or Urtica dioica? Which is more effective in ...

    African Journals Online (AJOL)

    Objectives: Diabetes mellitus, the most common endocrine disorder, is defined by hyperglycaemia. Urtica dioica or stinging nettle is known to have antidiabetic effects. Lamium album or non stinging nettle is shown to have some beneficial effects such as antioxidant, and cytoprotective properties. The purpose of this study ...

  2. Lamium album or urtica dioica?

    African Journals Online (AJOL)

    Proff.Adewunmi

    Objectives: Diabetes mellitus, the most common endocrine disorder, is defined by hyperglycaemia. Urtica dioica or stinging nettle is known to have antidiabetic effects. Lamium album or non stinging nettle is shown to have some beneficial effects such as antioxidant, and cytoprotective properties. The purpose of this study ...

  3. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

    International Nuclear Information System (INIS)

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D.; Lemasters, John J.

    2013-01-01

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca 2+ uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca 2+ uptake and suppressed the Ca 2+ -induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca 2+ uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective tetracyclines protect

  4. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Lemasters, John J., E-mail: JJLemasters@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC (United States)

    2013-11-15

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective

  5. Dietary, endocrine, and metabolic factors in the development of colorectal cancer.

    Science.gov (United States)

    Barone, Michele; Lofano, Katia; De Tullio, Nicola; Licinio, Raffaele; Licino, Raffaele; Albano, Francesca; Di Leo, Alfredo

    2012-03-01

    Colorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention. Epidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-β), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-β in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-β agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-β as compared to estrogen receptor alpha (ER-α), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention.

  6. Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community.

    Science.gov (United States)

    Tordjman, Karen; Grinshpan, Laura; Novack, Lena; Göen, Thomas; Segev, Dar; Beacher, Lisa; Stern, Naftali; Berman, Tamar

    2016-12-01

    Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P<0.001). In Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The Effect of Hydro-alcoholic Extract of Leaves of Vitex on the Gestation Indices of Male Rats

    Directory of Open Access Journals (Sweden)

    Fereshteh Ramezanloo

    2017-03-01

    Full Text Available Background: Phytoestrogens are some plant compounds with estrogenic biological effects which are found in many nutritional sources as soybean, flaxseed, and sesame. Vitex agnus-castus, also called Vitex, owns phytoestrogen properties. Studies have shown that phytoestrogens have different impacts on the gestation process and reproduction indices. Objective: The present study was aimed to investigate the effects of Vitex extract on the gestation indices in the male rat as well as studying its histological properties in the rat testicles. Materials and Methods: The hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg, vehicle (normal saline and the hydro-alcoholic powder of soybean (120 mg/kg were respectively given to understudy, vehicle and positive control groups for 49 days. After weighing the rats in the 1st and 49th days, the blood samples of all groups were taken and tested for estradiol levels, testosterones, FSH and LH.Moreover, such reproductive indices as sperm count, sperm motion, and prostate and testicle weight were studied and samples were collected for histological studies. Results: Prescription of the hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg did not change the rat’s weight, significantly (P-value= 0.06. Hormonal studies reduced the progesterone, LH, and FSH compared to the vehicle group, significantly (P-value<0.05. In addition, the amount of estradiol was significantly more than the vehicle group and the most effect was observed at a dose of 365 mg/kg (P-value=0.02. Histological studies showed a reduction in existing spermatozoa in the seminiferous ducts. Conclusions: This study had shown that the Vitex extract had inhibiting effects on the gestation indices in male rat and due to its destructive effects on the testicle tissues, more studies were required.

  8. Effects of three different formulae of Gamisoyosan on lipid accumulation induced by oleic acid in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Hiroe Go

    2017-12-01

    Full Text Available Background: Gamisoyosan (GSS is an herbal formula which has been used to treat women’s diseases for several hundred years in Korea. GSS is one of the three most common prescriptions among women and is used to treat menopausal symptoms. Fatty liver disease is also common in postmenopausal women and can precede more severe diseases, such as steatohepatitis. The present study compared the effects of GSS on fatty liver using three different formulae, Dongui-Bogam (KIOM A, Korean Pharmacopeia (KIOM B and Korean National Health Insurance (KIOM C. Methods: In oleic acid-induced HepG2 fatty liver cells, cellular lipid accumulation, triglycerides and total cholesterol were measured after treatment with three GSS formulae and simvastatin as a positive control. To investigate the phytoestrogen activity of GSS, MCF-7 cells were treated with GSS, and hormone levels were quantified. Also, qualitative analysis was performed with UPLC. Results: All types of GSS decreased cellular lipid accumulation. KIOM A was slightly less effective than the other two GSS formulae. KIOM B and KIOM C decreased cellular triglycerides more effective than simvastatin, but KIOM A did not affect cellular triglycerides. Cellular total cholesterol was decreased by all GSS and simvastatin. GSS showed phytoestrogen activity in MCF-7 cells. From the UPLC analysis data, geniposide, paeoniflorin and glycyrrhizin were detected form three GSS formulae. Conclusion: These results suggest that all GSS formulae have a beneficial effect on fatty liver disease during menopause and that differences of formula have no effect on the efficacy of the prescription. Keywords: fatty liver, Gamisoyosan, menopause, phytoestrogen

  9. Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension.

    Science.gov (United States)

    Prasad, Kailash

    2013-12-01

    Secoisolariciresionol diglucoside (SDG) is a plant lignan isolated from flaxseed and is phytoestrogen. SDG is a potent and long-acting hypotensive agent. Plant phytoestrogens have inhibitory effects on angiotensin-converting enzyme (ACE). The hypotensive effects of SDG, a phytoestrogen, may be mediated through inhibition of ACE. The objective of this study was to investigate if SDG-induced hypotension is mediated through inhibition of ACE. The Sprague Dawley male rats were anesthetized and trachea was cannulated. The right jugular vein was cannulated to administer the drug and the carotid artery was cannulated to record arterial pressures using PIOEZ-1 miniature model transducer (Becton, Dickinson and Company, Franklin Lakes, NJ) and Beckman dynograph (Beckman Instruments, Inc., Schiller Park, IL). The effects of angiotensin I (0.2 µg/kg, intravenously [IV]) in the absence and presence of SDG (10 mg/kg, IV), and SDG alone on systolic, diastolic, and mean arterial pressures were measured before and after 15, 30, and 60 minutes of drug administration. SDG decreased the systolic, diastolic, and mean arterial pressure by 37, 47, and 43%, respectively, at 15 minutes and 18.8, 21.2, and 20.3%, respectively, at 60 minutes. Angiotensin I increased the arterial pressure. SDG decreased angiotensin I-induced rise in the systolic, diastolic, and mean arterial pressures by 60, 58, and 51%, respectively, at 15 minutes and 48, 46, and 30%, respectively, at 60 minutes. The data suggest that SDG reduced the angiotensin I-induced rise in the arterial pressures and hence SDG is a potent ACE inhibitor.

  10. Consumption of indigenous medicines by pregnant women in North India for selecting sex of the foetus: what can it lead to?

    Science.gov (United States)

    Neogi, Sutapa Bandyopadhyay; Negandhi, Preeti H; Ganguli, Abhijit; Chopra, Sapna; Sandhu, Navraj; Gupta, Ravi Kant; Zodpey, Sanjay; Singh, Amarjeet; Singh, Arun; Gupta, Rakesh

    2015-09-04

    Sex ratio is an important indicator of development. Despite all the measures undertaken for improvement, it remains an issue of concern in India, with Haryana having a very low sex ratio in the country. Studies have been conducted indicating that consumption of indigenous drugs used for sex selection (SSD) could be strongly associated with adverse effects on the foetal development, including congenital malformations. Some samples of SSDs were collected from parts of North India and analysed in a standard laboratory for its components. Thirty SSDs used by the local community were procured from various sources in north India through a rigorous process of collection. These were subjected to laboratory tests to investigate the presence of phytoestrogen and testosterone. Following sample extraction, thin layer chromatography and high performance liquid chromatography were carried out for analysing phytoestrogen content. SSDs were available in various forms such as powder, tablets, mostly from faith healers. Around 87% of the samples collected from sources like doctors, quacks and faith healers were to be taken by the pregnant women after conception; 63% drugs were strongly positive for phytoestrogens (genistein, daidzein, formononetin) and 20% drugs were positive for testosterone. The average dose of the components as calculated after analyses was as follows: daidzein--14.1 mg/g sample, genistein--8.6 mg/g sample, formononetin--5 mg/g sample. These SSDs could be potentially detrimental to the growth and development of the foetus. This is likely to have implications on the health of the community. In view of the results obtained in our study, we strongly attest the importance in curbing this harmful practice by banning the supply of the drugs as well as by advocating behavioural changes in the community.

  11. Dioxin-like activity in environmental and human samples from Greenland and Denmark

    DEFF Research Database (Denmark)

    Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

  12. The effects of soy isoflavones on obesity

    DEFF Research Database (Denmark)

    Ørgaard, Anne; Jensen, Lotte

    2008-01-01

    factors in the development of Type II diabetes, cardiovascular disease, atherosclerosis, and certain cancers. Because of the lower frequency of these diseases in Asian countries, attention has been turned toward the Asian diet, which consists highly of soy and soy-based products. The health benefits...... associated with soy consumption have been linked to the content of isoflavones, the main class of the phytoestrogens. As a result of their structural similarities to endogenous estrogens, isoflavones elicit weak estrogenic effects by competing with 17beta-estradiol (E2) for binding to the intranuclear...

  13. Dioxin-like activity of environmental compounds in human blood and environmental samples

    DEFF Research Database (Denmark)

    Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

  14. Proliferative effect of whey from cow's milk obtained at two different stages of pregnancy measured in MCF-7 cells

    DEFF Research Database (Denmark)

    Nielsen, Tina S; Andersen, Charlotte; Sejrsen, Kristen

    2012-01-01

    Dietary estrogens may play a role in the etiology of hormone-dependent cancers like breast cancer. Cow's milk contains various endogenous estrogens and feed derived phytoestrogens that potentially contribute to an estrogenic effect of milk in consumers, and therefore we evaluated the effect of milk...... (whey) in a proliferation assay with estrogen-sensitive MCF-7 human breast cancer cells. Milk samples were obtained from 22 cows representing different stages of pregnancy (first and second half) and whey was produced from the milk. 0·1, 0·25 or 0·5% whey was included in the cell culture medium...

  15. Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model

    OpenAIRE

    Akram Ahangarpour; Seyedeh Asma Najimi; Yaghoob Farbood

    2016-01-01

    Background: Aging is associated with the loss of endocrine function. In this study, Vitex agnus-castus (Vitex), which has antioxidant effects and high levels of phytoestrogen, was investigated with regard to the hypothalamic-pituitary-gonadal axis and antioxidant indices in natural aging and in a d-galactose induced aging model in female mice. Methods: The mice were subcutaneously injected with d-galactose (500 mg/kg/d for 45 days). Extract of Vitex (600 mg/kg/bid for 7 days by gavage) was...

  16. MENOPAUSE AND NATURAL HEALING

    Directory of Open Access Journals (Sweden)

    Lucija Vrabič Dežman

    2008-12-01

    The studies could not decisively confirm the effectiveness of various phytoestrogens inamelioration of climacteric symptoms. Most studies have proven the effectiveness of thenatural medication made of Cimicifuga racemosa and its safe short-term use. Gynecologists should be familiar with the basics of phytotherapy and the results of clinical studiesin this field in order to confidently advise women to use the natural medications in caseswhere despite the climacteric symptoms they cannot or will not use HRT, consequentlygreatly reducing the quality of their lives. In cases where climacteric symptoms are mild tomoderate, some menopausal societies around the globe suggest trying natural medicationfirst, and only later implementing HRT

  17. The evaluation of the efficacy of sodium carbonate as zearalenone destructor in feeding stuffs.

    Science.gov (United States)

    Polak, M; Gajecki, M; Kulik, T; Łuczyński, M K; Obremski, K; Góra, M; Gajecka, M; Jakimiuk, E; Zielonka, Ł

    2009-01-01

    Contamination of feed with zearalenone (ZEA) is still a serious problem in farm animals feeding, especially in gilts, sensitive to this compound. The relative failure of current methods of decontamination and quality control lead us to look for new techniques. The commonly accepted method for breaking down ZEA was performed in controlled temperature and time conditions. Various sodium carbonate doses (0.5 - 4%) were added to feed naturally contaminated with ZEA (ZEA biosynthesis by F. graminearum isolates). These doses were found to be effective in in vitro studies. The addition of 2% sodium carbonate gave the best results in reducing the phytoestrogen in the feed.

  18. Reversal of Estrogen Receptor Beta Epigenetic Gene Silencing in Prostatic Adenocarcinoma by Soy Protein-Derived Isoflavonoid Supplementation

    Science.gov (United States)

    2009-06-01

    Japanese men. Cancer Sci 95, 65-71 (2004). 85. Goetzl, M.A., Van Veldhuizen , P.J. & Thrasher, J.B. Effects of soy phytoestrogens on the prostate...radical prostatectomy. Am J Surg Pathol 28, 928-34 (2004). 63. Noordzij, M.A., Bogdanowicz, J.F., van Krimpen, C., van der Kwast, T.H. & van ...accumulation in prostatic fluid in caucasian men. J Nutr 135, 1400-6 (2005). 118. Hedlund, T.E., van Bokhoven, A., Johannes, W.U., Nordeen, S.K. & Ogden, L.G

  19. Crystalline lens radioprotectors

    International Nuclear Information System (INIS)

    Belkacemi, Y.; Pasquier, D.; Castelain, B.; Lartigau, E.; Warnet, J.M.

    2003-01-01

    During more than a half of century, numerous compounds have been tested in different models against radiation-induced cataract. In this report, we will review the radioprotectors that have been already tested for non-human crystalline lens protection. We will focus on the most important published studies in this topic and the mechanisms of cyto-protection reported in. vitro and in. vivo from animals. The most frequent mechanisms incriminated in the cyto-protective effect are: free radical scavenging, limitation of lipid peroxidation, modulation of cycle progression increase of intracellular reduced glutathione pool, reduction of DNA strand breaks and limitation of apoptotic cell death. Arnifostine (or Ethyol) and anethole dithiolethione (or Sulfarlem), already used clinically as chemo- and radio-protectants, could be further test?r for ocular radioprotection particularly for radiation-induced cataract. (author)

  20. Two New Stilbenoids from the Aerial Parts of Arundina graminifolia (Orchidaceae

    Directory of Open Access Journals (Sweden)

    Florence Auberon

    2016-10-01

    Full Text Available Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1 and a 9,10-dihydrophenanthrene named arundigramin (2 together with a known lignin dimer (3 and seven known stilbenoids (4–10 were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC, heteronuclear multiple-bond correlation spectroscopy (HMBC, and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability while the other compounds showed no significant activity at the highest concentration tested.

  1. Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in cultured guinea pig gastric mucosal cells.

    Science.gov (United States)

    Hoshino, Tatsuya; Takano, Tatsunori; Tomisato, Wataru; Tsutsumi, Shinji; Hwang, Hyun-Jung; Koura, Yuko; Nishimoto, Kiyo; Tsuchiya, Tomofusa; Mizushima, Tohru

    2003-01-01

    We previously reported that several gastric irritants, including ethanol, hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in cultured gastric mucosal cells. In the present study, we examined the effects of sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced necrosis in primary cultures of guinea pig gastric mucosal cells. The preincubation of cells with sucralfate was not necessary for its cytoprotective effect to be observed, thus making its mechanism of action different from that of other gastroprotective drugs. Necrosis of gastric mucosal cells induced by hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo can be explained, at least in part, by its inhibitory effect on gastric irritant-induced necrosis.

  2. Melatonin, mitochondria, and the metabolic syndrome.

    Science.gov (United States)

    Cardinali, Daniel P; Vigo, Daniel E

    2017-11-01

    A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

  3. Antiulcerogenic effects of coconut (Cocos nucifera) extract in rats.

    Science.gov (United States)

    Nneli, R O; Woyike, O A

    2008-07-01

    A warm water crude extract of coconut milk and a coconut water dispersion were investigated for their antiulcerogenic effects in male Wistar albino rats. Ulcers were induced in the male rats by subcutaneous administration of indomethacin (40 mg/kg) using standard procedures. The ulcer inhibition rate (UIR) was taken as a measure of the cytoprotection offered by test substances. Coconut milk (2 mL daily oral feeding) produced a stronger percentage (54%) reduction in the mean ulcer area than coconut water (39%). The effect of coconut milk was similar to the effect of sucralfate that reduced the mean ulcer area by 56% in this study. Sucralfate is a conventional cytoprotective agent. The results showed that coconut milk and water via macroscopic observation had protective effects on the ulcerated gastric mucosa. It is concluded that coconut milk offered stronger protection on indomethacin-induced ulceration than coconut water in rats.

  4. Thiazoline peptides and a tris-phenethyl urea from Didemnum molle with anti-HIV activity.

    Science.gov (United States)

    Lu, Zhenyu; Harper, Mary Kay; Pond, Christopher D; Barrows, Louis R; Ireland, Chris M; Van Wagoner, Ryan M

    2012-08-24

    As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey's method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC(50) values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC(50) value of 60 μM.

  5. Immunohistochemical localization of epidermal growth factor in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands is...... antisera against human urinary EGF worked in rat as well as man. EGF was found only in cells with an exocrine function.......Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands...... is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  6. Pharmacological activation of mitochondrial BKCa channels protects isolated cardiomyocytes against simulated reperfusion-induced injury

    Czech Academy of Sciences Publication Activity Database

    Borchert, Gudrun H.; Hlaváčková, Markéta; Kolář, František

    2013-01-01

    Roč. 238, č. 2 (2013), s. 233-241 ISSN 1535-3702 R&D Projects: GA AV ČR(CZ) IAA500110804; GA ČR(CZ) GAP303/12/1162 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : potassium channels * cardiomyocytes * mitochondria * ischemia/reperfusion * cytoprotection * reactive oxygen species Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.226, year: 2013

  7. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    OpenAIRE

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). METHODS: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the pre...

  8. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    OpenAIRE

    van Loon, Rosa Laura E.; Bartelds, Beatrijs; Wagener, Frank A. D. T. G.; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W. C.; Takens, Janny; Berger, Rolf M. F.

    2015-01-01

    Background Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). Methods Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO i...

  9. Silybin a silymarin - new and emerging applications in medicine

    Czech Academy of Sciences Publication Activity Database

    Gažák, Radek; Walterová, D.; Křen, Vladimír

    2007-01-01

    Roč. 14, č. 3 (2007), s. 315-338 ISSN 0929-8673 R&D Projects: GA MŠk(CZ) LC06010; GA MŠk OC 136; GA MŠk 1P05OC073 Institutional research plan: CEZ:AV0Z50200510 Keywords : silybin * silymarin * cytoprotective activity Subject RIV: CE - Biochemistry Impact factor: 4.944, year: 2007

  10. Alcohol in Moderation, Cardioprotection and Neuroprotection: Epidemiological Considerations and Mechanistic Studies

    OpenAIRE

    Collins, Michael A.; Neafsey, Edward J.; Mukamal, Kenneth J.; Gray, Mary O.; Parks, Dale A.; Das, Dipak K.; Korthuis, Ronald J.

    2008-01-01

    In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating beneficial effects of light-moderate, non-binge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alco...

  11. The Multiple Facets of Lutein: A Call for Further Investigation in the Perinatal Period

    OpenAIRE

    Perrone, Serafina; Tei, Monica; Longini, Mariangela; Buonocore, Giuseppe

    2016-01-01

    Lutein may have important antioxidant actions in free-radical-mediated diseases, in addition to its well-known antioxidant and cytoprotective effects on macula and photoreceptors. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as lutein could help to prevent or at least to reduce oxidative stress related diseases in newborns. Since lutein is not synthesized by humans, the intake primarily depends on diet or supplementation. Newborns r...

  12. ERK controls epithelial cell death receptor signalling and cellular FLICE-like inhibitory protein (c-FLIP) in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Vainer, Ben

    2013-01-01

    Intestinal epithelial cell (IEC) death signalling through the Fas receptor is impaired in active ulcerative colitis (UC). This is possibly due to the activation of cytoprotective pathways resulting in limitation of the tissue injury secondary to inflammation. We hypothesized that inflammatory...... the resistance to receptor mediated epithelial apoptosis in active UC. Oncogenic c-FLIP could promote propagation of DNA-damaged IECs and contribute to cancer development in UC....

  13. Sorafenib-induced defective autophagy promotes cell death by necroptosis

    OpenAIRE

    Kharaziha, Pedram; Chioureas, Dimitris; Baltatzis, George; Fonseca, Pedro; Rodriguez, Patricia; Gogvadze, Vladimir; Lennartsson, Lena; Bj?rklund, Ann-Charlotte; Zhivotovsky, Boris; Grand?r, Dan; Egevad, Lars; Nilsson, Sten; Panaretakis, Theocharis

    2015-01-01

    Autophagy is one of the main cytoprotective mechanisms that cancer cells deploy to withstand the cytotoxic stress and survive the lethal damage induced by anti-cancer drugs. However, under specific conditions, autophagy may, directly or indirectly, induce cell death. In our study, treatment of the Atg5-deficient DU145 prostate cancer cells, with the multi-tyrosine kinase inhibitor, sorafenib, induces mitochondrial damage, autophagy and cell death. Molecular inhibition of autophagy by silencin...

  14. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    BACKGROUND: Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using...... contribution from compensatory mechanisms to the phenotype following a genetic perturbation. We also stress, that care should be taken when comparing results where different mouse strains and colonies have been used due to large genetic background contribution to the observed phenotype....

  15. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  16. Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

    Science.gov (United States)

    2017-04-01

    on MPNSTs. The drugs that we are testing are approved for human use and could be rapidly advanced into human MPNST clinical trials if our pre...would kill normal cells. Cytoprotective autophagy can be inhibited by lysosomotropic agents such as chloroquine (CQ) that inhibit lysosome degradation...therapeutically useful at least in part by virtue of their ability to suppress CXCL12 expression. Page 6 Figure 1: AT101 down-regulates CXCL12

  17. ORGANOPROTECTIVE EFFECTS OF BENASEPRIL IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. S. Zadionchenko

    2006-01-01

    Full Text Available Aim. To evaluate antihypertensive efficiency of benasepril therapy (Lotensin, Novartis and its effects on microcirculation, endothelium function, system of cytoprotection, ophthalmoscopic and functional characteristics of eye retina in patients with arterial hypertension (AH. Material and methods. 40 patients with AH of 1-3 degree (AH1, AH2, and AH3 were studied. After wash-out period all patients were prescribed benasepril 5-10 mg daily. If necessary, hydrochlorothiazide 12,5 mg daily was added. Treatment lasted during 6 months. Patients were examined at the beginning and at the end of the study. Ambulatory blood pressure (BP monitoring was carried out. Microcirculation was assessed by method of laser Doppler flowmetry. Stable plasma metabolites of nitric oxide (NO were determined by spectral photometry. Cytoprotection was assessed by content of heat shock proteins (HSP70 in leucocytes of peripheral blood. Ophthalmoscopy, color and contrast static campimetry with evaluation of sensory-motor reaction (SMR time in different fields of vision were carried out. Results. Therapy with benasepril allowed to improve daily profile of BP and to reach its target level in all AH patients. Number of patients with spastic type of microcirculation decreased. Functional condition of endothelium improved which revealed in normalization of endothelial production of NO. Therapy with benasepril resulted in intracellular HSP70 level decrease which testified restriction of cellular destruction. The cytoprotective effect of benasepril was stronger in patient with severe AH. Therapy with benasepril resulted in SMR time decrease which signifies its positive influence on retinal blood flow. Evaluation of contrast and color sensitiveness of retina allowed to reveal and quantitatively assess earlier dysfunctions of retinal tissue perfusion, compared to ophthalmoscopy. Conclusion. Benasepril is an efficient antihypertensive drug which improves microcirculation, endothelium

  18. A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection.

    Directory of Open Access Journals (Sweden)

    Takuya Kanno

    Full Text Available Therapeutic agents to the central nervous system (CNS need to be efficiently delivered to the target site of action at appropriate therapeutic levels. However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. We have previously reported the novel small-molecule compound, 2-[mesityl(methylamino]-N-[4-(pyridin-2-yl-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316, as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS. One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG and hemopexin (HPX, requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy.

  19. Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

    OpenAIRE

    Maida Rakanović-Todić; Lejla Burnazović-Ristić; Slavka Ibrulj; Nedžad Mulabegović

    2014-01-01

    Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of t...

  20. The Anti-Apoptotic Activity of BAG3 Is Restricted by Caspases and the Proteasome

    OpenAIRE

    Virador, Victoria M.; Davidson, Ben; Czechowicz, Josephine; Mai, Alisha; Kassis, Jareer; Kohn, Elise C.

    2009-01-01

    Background Caspase-mediated cleavage and proteasomal degradation of ubiquitinated proteins are two independent mechanisms for the regulation of protein stability and cellular function. We previously reported BAG3 overexpression protected ubiquitinated clients, such as AKT, from proteasomal degradation and conferred cytoprotection against heat shock. We hypothesized that the BAG3 protein is regulated by proteolysis. Methodology/Principal Findings Staurosporine (STS) was used as a tool to test ...

  1. Mineral and/or milk supplementation of fruit beverages helps in the prevention of H2O2-induced oxidative stress in Caco-2 cells La adición de minerales y/o leche a bebidas a base de zumo de frutas ayuda en la prevención del estrés oxidativo inducido por H2O2 en celulas Caco-2

    OpenAIRE

    A. Cilla; J. M. Laparra; A. Alegria; R. Barbera

    2011-01-01

    Introduction: Fruit beverages are commonly supplemented with milk, vitamins and/or minerals in order to improve their healthy effects by providing some bioactive components that can act additively or synergistically against oxidative stress. Aims: To test whether iron, zinc, and milk added to fruit beverages do not affect the cytoprotective effect against oxidative damage to Caco-2 cells through GSH-related enzymes induction and cell cycle progression preservation, in comparison with non-supp...

  2. Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

    OpenAIRE

    Zhang, Liang; Zhou, Liwei; Du, Jia; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Peng, Yang; Xie, Jiayin; Wang, Dong

    2014-01-01

    Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the pr...

  3. Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

    International Nuclear Information System (INIS)

    Mao, Haoping; Wang, Hong; Ma, Shangwei; Xu, Yantong; Zhang, Han; Wang, Yuefei; Niu, Zichang; Fan, Guanwei; Zhu, Yan; Gao, Xiu Mei

    2014-01-01

    Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p + (p + induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion. • Bakuchiol may have anti-stress and the potential anti-depression-like effects

  4. [Benefits of moderate beer consumption at different stages of life of women].

    Science.gov (United States)

    Pérez Medina, Tirso; de Argila Fernández-Durán, Nuria; Pereira Sánchez, Augusto; Serrano González, Lucía

    2015-07-18

    Beer is a natural beverage low calorie, low degree of alcohol, no fats or sugars and a significant amount of carbohydrates, vitamins, and proteins. Beneficial health qualities are based on the presence in the beer of antioxidant compounds (polyphenols), which reduce the presence of free radicals in the organism, and phytoestrogens, elements biosimilars to natural estrogens. In pregnant women, beer, obviously alcohol-free, presents elements in its composition that differ it from other fermented beverages as it is the folic acid, vitamin necessary to prevent defects of the neural tube in the fetus or regulate homocysteine. With regard to breastfeeding, beer alcohol-free supplementation increases the antioxidant activity in breast milk and therefore reduces the oxidative stress of the newborn after birth In menopause, the presence of antioxidants, vitamins, nutrients, and dietetic fiber, as well as phytoestrogens, is highly beneficial in the prevention of pathologies arising from the decline in estrogens. Osteoporosis also is effectively combated by the beer. The intake of beer, favors a greater bone mass in women, irrespective of their gonadal status. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets--importance and approaches for laboratory animal research.

    Science.gov (United States)

    Heindel, Jerrold J; vom Saal, Frederick S

    2008-03-01

    We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research.

  6. Multiresidue analysis of oestrogenic compounds in cow, goat, sheep and human milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in micro-dispersive solid-phase extraction followed by ultra-high-performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Socas-Rodríguez, Bárbara; Hernández-Borges, Javier; Herrera-Herrera, Antonio V; Rodríguez-Delgado, Miguel Ángel

    2018-03-01

    In this work, the suitability of Fe 3 O 4 nanoparticles coated with polydopamine was evaluated as sorbent for the extraction of a group of 21 compounds with oestrogenic activity including seven phytoestrogens, six mycotoxins as well as four synthetic and four natural oestrogens from different types of milk, including sheep milk, in which the evaluation of oestrogenic compounds have never been developed before. Extraction was carried out using magnetic micro-dispersive solid-phase extraction after a previous deproteinisation step. Separation, determination and quantification of the target analytes were achieved by ultra-high-performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry. The methodology was validated for five milk samples using 17β-estradiol-2,4,16,16,17-d 5 as internal standard for natural and synthetic oestrogens, β-zearalanol-10,10,11,12,12-d 5 for mycotoxins and prunetin for phytoestrogens. Recovery values ranged from 70 to 120% for the five types of matrices with relative standard deviation values lower than 18%. Limits of quantification of the method were in the range 0.55-11.8 μg L -1 for all samples. Graphical abstract General scheme of the multiresidue analysis of oestrogenic compounds in milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in μ-dSPE.

  7. Biochanin a and Daidzein Influence Meiotic Maturation of Pig Oocytes in a Different Manner

    Directory of Open Access Journals (Sweden)

    Hošková K.

    2014-09-01

    Full Text Available The aim of the study was to determine the influence of different concentrations of phytoestrogens biochanin A (BIO A; 20, 40, 50μg ml-1 and daidzein (DAI; 10, 20, 40, 50μg ml-1 on the course of meiotic maturation of pig oocytes. After a 24-hour cultivation, a stage of nuclear maturation was achieved and the areas of cumulus-oocyte complexes (COCs, as an indicator of cumulus expansion, were evaluated. The effects of both contaminants on oocytes were mani - fested from the lowest concentration used. Nuclear maturation was inhibited in a dose-dependent manner in the case of BIO A. Effects of DAI reached a plateau at a concentration of 20μg ml-1.Possible relationship to limited solubility of DAI was excluded because limits of DAI solubility in culture medium were confirmed at 50 μg ml-1.The cumulus expansion was also influenced in a different manner - reduction of the COC’s area by BIO A was dose-dependent, whereas DAI had the strongest effect on CCs in the lowest and highest concentrations used. Both phytoestrogens negatively influence the meiotic maturation of porcine oocytes but there are significant differences in their concrete effects which could relate to the diverse mechanisms of their acting on target cells.

  8. In Utero and Lactational Effects of Aqueous Foeniculum Vulgare (Fennel Seed Extract on Puberty Timing, Estrus Cycle and Sexual Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Rahmatollah Parandin

    2018-02-01

    Full Text Available Abstract Background: Several studies have shown that developmental exposure to phytoestrogens causes adverse effects on the reproductive functions. Fennel as a phytoestrogen plant has a rich history in household use and traditional medicine.So, the current study was designed to investigate the effects of in utero and neonatal exposure with fennel on the puberty onset, estrus cycle, reproductive organs and sexual behavior of their offspring. Materials and Methods: BALB/c mice were injected intraperitoneally with 0 (control, 100, 200 and 400 (mg/kg bw aqueous fennel seed extract (AFSE, daily from day 7 of gestation to postnatal day (PND 7. Results: Vaginal opening (sign of puberty onset was advanced in 200 (p<0.01 and 400 AFSE (p<0.001 treated females. A 30 days vaginal smear check indicated that 200 or 400 AFSE treated mice showed a prolonged estrus with decreased proestrus, estrus and metestrus stages and increased and diestrus stage and index. The ovary weight, number of corpora lutea and LH concentration decreased and uterus weight and estradiol concentration increased in the 200 or 400 treated mice in PND 70. 400 AFSE (p<0.01 treated females showed lordosis with a low lordosis quotient (LQ when compared to the control group. Conclusion: These results suggest that developmental exposure to AFSE, due to its estrogenic compounds, it may cause the precocious puberty, disrupted estrus cycle, altered weight of reproductive organs, hormonal imbalance and low lordosis behavior.

  9. Topical isoflavones provide effective photoprotection to skin.

    Science.gov (United States)

    Lin, Jing-Yi; Tournas, Joshua A; Burch, James A; Monteiro-Riviere, Nancy A; Zielinski, Jan

    2008-04-01

    Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone-mediated photoprotection with the pig skin model, a more human-resembling model. The pig skin was treated with five well-known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar-simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1-MED intervals. Evaluation was carried out 24 h later by colorimeter-measured erythema and sunburn cell numbers. Topical application of 0.5% solutions of three individual phytoestrogens - genistein, daidzein, biochanin A - are better than similar solutions of equol or formononetin in protecting pig skin from solar-simulated ultraviolet (SSUV)-induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L-ascorbic acid, 1%alpha-tocopherol, and 0.5% ferulic acid. Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.

  10. Compounds from Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.

    Science.gov (United States)

    Wang, Xueni; Tao, Rui; Yang, Jing; Miao, Lin; Wang, Yu; Munyangaju, Jose Edouard; Wichai, Nuttapong; Wang, Hong; Zhu, Yan; Liu, Erwei; Chang, Yanxu; Gao, Xiumei

    2017-01-01

    To investigate the phytoestrogenic and phytoandrogenic activities of compounds isolated from CS and uncover the role of CS in prevention of oestrogen/androgen-induced BPH. Cells were treated with CS compounds, and immunofluorescence assay was performed to detect the nuclear translocation of ER α or AR in MCF-7 or LNCaP cells; luciferase reporter assay was performed to detect ERs or AR transcriptional activity in HeLa or AD293 cells; MTT assay was performed to detect the cell proliferation of MCF-7 or LNCaP cells. Oestrogen/androgen-induced BPH model was established in rat and the anti-BPH, anti-estrogenic, and anti-androgenic activities of CS in vivo were further investigated. The nuclear translocation of ER α was stimulated by nine CS compounds, three of which also stimulated AR translocation. The transcriptional activities of ER α and ER β were induced by five compounds, within which only ECG induced AR transcriptional activity as well. Besides, ECG stimulated the proliferation of both MCF-7 cells and LNCaP cells. CS extract suppressed oestrogen/androgen-induced BPH progress in vivo by downregulation of E2 and T level in serum and alteration of the expressions of ER α , ER β , and AR in the prostate. Our data demonstrates that compounds from CS exhibit phytoestrogenic and phytoandrogenic activities, which may contribute to inhibiting the oestrogen/androgen-induced BPH development.

  11. Genistein and daidzein: different molecular effects on prostate cancer.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2013-01-01

    Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

  12. Plasma isoflavones in Malaysian men according to vegetarianism and by age.

    Science.gov (United States)

    Hod, Rafidah; Kouidhi, Wided; Ali Mohd, Mustafa; Husain, Ruby

    2016-01-01

    Epidemiological studies indicate lower prevalences of breast and prostate cancers and cardiovascular disease in Southeast Asia where vegetarianism is popular and diets are traditionally high in phytoestrogens. This study assessed plasma isoflavones in vegetarian and non-vegetarian Malaysian men according to age. Daidzein, genistein, equol (a daidzein metabolite), formononetin, biochanin A, estrone, estradiol and testosterone were measured by validated liquid chromatography tandem mass spectrometry (LCMSMS). Plasma isoflavone and sex hormone concentrations were measured in 225 subjects according to age (18-34, 35-44 and 45-67 years old). In all age groups, vegetarians had a higher concentration of circulating isoflavones compared with non-vegetarians especially in the 45-67 year age group where all isoflavones except equol, were significantly higher in vegetarians compared with omnivores. By contrast, the 18-34 year group had a significantly higher concentration of daidzein in vegetarians and significantly higher testosterone and estrone concentrations compared with non-vegetarians. In this age group there were weak correlations between estrone, estradiol and testosterone with some of the isoflavones. This human study provides the first Malaysian data for the phytoestrogen status of vegetarian and nonvegetarian men.

  13. Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

    Science.gov (United States)

    Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

    2017-12-01

    Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

  14. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

    Science.gov (United States)

    Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

    2009-08-01

    The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

  15. A study of the red clover extract trinovin by ESR HPLC/MS and UVS

    International Nuclear Information System (INIS)

    Troup, G.; Hutton, D.; Hunter, C.; Hewitt, D.; Mulinacci, N.; Romani, A.; Pinelli, P.; Mancini, P.

    1999-01-01

    Full text: Trinovin is an extract of red clover, recently released on the dietary supplement market. It is recommended for 'Men's Health', because it contains the phenolics (isoflavones) genistein, biochanin, daidzein and formononetin, said to act as 'phytoestrogens', and is therefore a possible help in prostate gland problems. An Electron Spin Resonance (ESR) study (∼9.1Ghz, room temperature) revealed at least 3 different free radical lines, one with hyperfine structure, consistent with the listed molecules. Accordingly, HPLC/DAD (High Performance Liquid Chromatography/Diode Array Detector) and HPLC/Mass Spectroscopy analyses were performed in order to evaluate the quali-quantitative contents of flavonoidic compounds. The HPLC profile shows two main isoflavones and another three compounds, one of them being a quercetin glycoside. The quercetin glycosides are flavonoidic derivatives abundant in plant materials and present in wine. We can therefore say: even if the phytoestrogen properties claimed for Trinovin turn out to be less than hoped for, the antioxidants contained are very powerful, and so possibly helpful in protection against many diseases, including cancers, atherosclerosis, diabetic retinal bleeding, and non-alcoholic dementia

  16. THE DISORDERS OF THE LIPID METABOLISM IN THE EXPERIMENTAL ESTROGENIC DEFICIENCY AND THE EFFECT OF THE VEGETAL ANTIOXIDANTS DIET

    Directory of Open Access Journals (Sweden)

    Daniela Badoi

    2012-03-01

    Full Text Available In our days we have a great number of cardiovascular diseases with atherosclerotic etiopathogeny. That`s whythere is a important preocupation for identifying the atherogenic risk factors (lipid metabolism disorders. This studyfollows the effects of the ovarian hormones deficit in surgical menopause (experimental ovariectomy. The absence of theendogen estrogens disrupts the lipid metabolism and diminishes the antioxidant capacity. Another goal was to evaluatethe lipid profile improved by taking a flax seed diet rich in phytoestrogens. The experiment will be performed on whiterats, females, of the Wistar race. The supplementary diet with flax seeds will be administered to the ovariectomizedgroups as well as to the control groups. In the case of animals with a hormonal deficit (ovariectomy we found thepresence of dyslipidemia: hypercholesterolemia and/or hypertriglyceridemia. Supplementing the diet with flax seeds ledto the decreasing of the total seric cholesterol (p>0.05 and of the seric triglycerides (p0.05, after supplementing the diet with whole flax seeds, which suggests the protection of theendothelium, with the diminishing of the risk of triggering endothelial dysfunction. These results demonstrate thebeneficial effects of phytoestrogens from flax seed on lipid metabolism in experimental menopause.

  17. Improvement of Bone-Sparing Effect of Soy Isoflavones by Pre- and Probiotics in Postmenopausal women

    Directory of Open Access Journals (Sweden)

    J. Mathey

    2008-01-01

    Full Text Available Background Phytoestrogens consumption is targeted as a possible way to achieve hormonal permeation in postmenopausal women. However, their health effect could depend on their bioavailability. Objectives As phytoestrogens bioavailability could be improved by modulating intestinal microflora, the present study was undertaken to investigate whether isoflavones and pre-or probiotics may improve bone markers. Design An intervention trial (2 months was carried out on 39 postmenopausal women receiving 100 mg of IF aglycon equivalents daily, incorporated in two jelly milk and two cereal bars. After the first month, the participants were randomised into three treatment groups: soy (control group, soy + fructooligosaccharides (prebiotics group and soy + yoghurt cultures (probiotics group. Results Level of isoflavone intake was associated with a significant increase in plasma isoflavone levels from baseline to day 15 which was maintained until day 60. Probiotics consumption was associated with increased plasma equol levels at day 60. A 5% increase of bone alkaline phosphatase was elicited on day 30, compared to initial values. Pre- or probiotics did not modulate this parameter. Urinary deoxypyridinoline excretion was slightly increased at day 60. Prebiotics and probiotics consumption improved this parameter. The effect of prebiotics was exacerbated in early compared to late postmenopausal women. Conclusion Addition of prebiotics or probiotics to a diet providing isoflavones is able to improve parameters of bone turnover in early menopause.

  18. In vitro isoflavonoid production and analysis in natural tetraploid Trifolium pratense (red clover calluses

    Directory of Open Access Journals (Sweden)

    Tugba Ercetin

    2012-09-01

    Full Text Available Isoflavones are polyphenolic phytoestrogens, predominantly found in leguminous plants. Trifolium pratense L., Fabaceae (red clover, is rich in isoflavones that possess estrogenic activity due to their similar molecular structure and effectiveness in preventing health conditions such as menopause, osteoporosis, cardiovascular disease, hypertension and hormone-dependent cancers. In this study, presence and amount of various phytoestrogens in the tetraploid plant and in the calluses derived from the plants were investigated. Calluses were generated from explants obtained from natural tetraploid T. pratense seedlings. The best callus formation was obtained from hypocotyl explants cultured in Phillips Collins and Gamborg B5 media containing different plant growth regulators. Flowers of plants and calluses were analysed for formononetin, biochanin A, genistein and daidzein contents using HPLC. In HPLC analysis, high levels of formononetin (0.249 µg/mg were determined in natural tetraploid T. pratense flowers in addition to genistein and biochanin A. In calluses, highest isoflavone content (1.15 µg/mg formononetin was observed in modified Gamborg B5 medium. Biochanin A content of calluses and the plant were found to be nearly the same. But formononetin and genistein contents of the calluses in this medium were found to be respectively 4.62 and 21.39 folds higher than the tetraploid plant.

  19. In vitro isoflavonoid production and analysis in natural tetraploid Trifolium pratense (red clover calluses

    Directory of Open Access Journals (Sweden)

    Tugba Ercetin

    2012-10-01

    Full Text Available Isoflavones are polyphenolic phytoestrogens, predominantly found in leguminous plants. Trifolium pratense L., Fabaceae (red clover, is rich in isoflavones that possess estrogenic activity due to their similar molecular structure and effectiveness in preventing health conditions such as menopause, osteoporosis, cardiovascular disease, hypertension and hormone-dependent cancers. In this study, presence and amount of various phytoestrogens in the tetraploid plant and in the calluses derived from the plants were investigated. Calluses were generated from explants obtained from natural tetraploid T. pratense seedlings. The best callus formation was obtained from hypocotyl explants cultured in Phillips Collins and Gamborg B5 media containing different plant growth regulators. Flowers of plants and calluses were analysed for formononetin, biochanin A, genistein and daidzein contents using HPLC. In HPLC analysis, high levels of formononetin (0.249 µg/mg were determined in natural tetraploid T. pratense flowers in addition to genistein and biochanin A. In calluses, highest isoflavone content (1.15 µg/mg formononetin was observed in modified Gamborg B5 medium. Biochanin A content of calluses and the plant were found to be nearly the same. But formononetin and genistein contents of the calluses in this medium were found to be respectively 4.62 and 21.39 folds higher than the tetraploid plant.

  20. The regulation of steroid receptors by epigallocatechin-3-gallate in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Hallman K

    2017-05-01

    Full Text Available Kelly Hallman,* Katie Aleck,* Meghan Quigley, Brigitte Dwyer, Victoria Lloyd, Monica Szmyd, Sumi Dinda Biomedical Diagnostic and Therapeutic Sciences, School of Health Sciences, Center for Biomedical Research, Oakland University, Rochester, MI, USA *These authors contributed equally to this work Abstract: It has been reported that phytoestrogen epigallocatechin gallate (EGCG suppresses cancer cell proliferation and may have antitumor properties. In this study, we analyzed the effects of EGCG on estrogen receptor α (ERα and progesterone receptor in hormone-dependent T-47D breast cancer cells. Western blot analysis revealed EGCG induced a concentration-dependent decrease in ERα protein levels, with a 56% reduction occurring with 60 µM EGCG when compared to controls. Downregulation of ERα protein levels was observed after 24-hour co-treatment of T-47D cells with 60 µM EGCG and 10 nM 17β-estradiol (E2. The proliferative effect of E2 on cell viability was reversed when treated in combination with EGCG. In contrast, the combination of EGCG with the pure ER antagonist, ICI 182, 780, showed no further reduction in cell number as only 5% of the cells were viable after 6 days of treatment. These studies may provide further understanding of the interactions among flavonoids and steroid receptors in breast cancer cells. Keywords: phytoestrogen, ER, PR, T-47D, antiestrogens

  1. Biochanin-A antagonizes the interleukin-1β-induced catabolic inflammation through the modulation of NFκB cellular signaling in primary rat chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Su [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Cho, In-A; Kang, Kyeong-Rok [Department of Dental Bioengineering, Chosun University, Gwangju, 61452 (Korea, Republic of); You, Jae-Seek [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Yu, Sang-Joun [Department of Periodontology, Chosun University, Gwangju, 61452 (Korea, Republic of); Lee, Gyeong-Je [Department of Prosthodontics, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Yo-Seob [Department of Oral and Maxillofacial Radiology, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Chun Sung; Kim, Do Kyung [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Su-Gwan [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Young-Woo [Korea Basic Science Institute, Gwangju Center, Chonnam National University, Gwangju, 61186 (Korea, Republic of); Im, Hee-Jeong [Department of Biochemistry, Rush University Medical Center, Chicago, IL, 60612 (United States); Kim, Jae-Sung, E-mail: js_kim@chosun.ac.kr [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of)

    2016-09-02

    Biochanin-A, a phytoestrogen derived from herbal plants, protected from the IL-1β-induced loss of proteoglycans through the suppression of matrix degrading enzymes such as matrix metalloproteinase (MMP)-13, MMP-3, MMP-1, and ADAMTS-5 in primary rat chondrocytes and the knee articular cartilage. It also suppressed the expression of IL-1β-induced catabolic factors such as nitric oxide synthase 2, cyclooxygenase-2, prostaglandin E{sub 2}, and inflammatory cytokines. Furthermore, biochanin-A suppressed the IL-1β-induced phosphorylation of NFκB, and inhibited its nuclear translocation in primary rat chondrocytes. These results indicate that biochanin-A antagonizes the IL-1β-induced catabolic effects through its anti-inflammatory activity that involves the modulation of NFκB signaling. - Highlights: • Biochanin-A is a phytoestrogen derived from medicinal plants. • It suppressed the IL-1β-induced matrix degrading enzymes and catabolic factors. • It inhibited IL-1β-induced proteoglycan loss in chondrocytes and cartilage tissues. • Its anti-catabolic effects were mediated by modulation of NFκB signaling. • It may be used as a potential anti-catabolic biomaterial for osteoarthritis.

  2. Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Praveen Kumar

    2014-01-01

    Full Text Available Withania somnifera (Ashwagandha, also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM resulted in normalization of glial fibrillary acidic protein (GFAP expression as well as heat shock protein (HSP70, mortalin, and neural cell adhesion molecule (NCAM expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx levels, catalase, and superoxide dismutase (SOD but not reduced glutathione (GSH contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.

  3. Biochemical signaling by remote ischemic conditioning of the arm versus thigh: Is one raise of the cuff enough?

    Directory of Open Access Journals (Sweden)

    Cameron Dezfulian

    2017-08-01

    Full Text Available Remote Ischemic Conditioning (RIC, induced by brief cycles of ischemia and reperfusion, protects vital organs from a prolonged ischemic insult. While several biochemical mediators have been implicated in RIC's mechanism of action, it remains unclear whether the localization or “dose” of RIC affects the extent of protective signaling. In this randomized crossover study of healthy individuals, we tested whether the number of cycles of RIC and its localization (arm versus thigh determines biochemical signaling and cytoprotection. Subjects received either arm or thigh RIC and then were crossed over to receive RIC in the other extremity. Blood flow, tissue perfusion, concentrations of the circulating protective mediator nitrite, and platelet mitochondrial function were measured after each RIC cycle. We found that plasma nitrite concentration peaked after the first RIC cycle and remained elevated throughout RIC. This plasma nitrite conferred cytoprotection in an in vitro myocyte model of hypoxia/reoxygenation. Notably, though plasma nitrite returned to baseline at 24 h, RIC conditioned plasma still mediated protection. Additionally, no difference in endpoints between RIC in thigh versus arm was found. These data demonstrate that localization and “dose” of RIC does not affect cytoprotection and further elucidate the mechanisms by which nitrite contributes to RIC-dependent protection.

  4. Functionalized mesoporous silica nanoparticles for oral delivery of budesonide

    Energy Technology Data Exchange (ETDEWEB)

    Yoncheva, K., E-mail: krassi.yoncheva@gmail.com [Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia (Bulgaria); Popova, M. [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Szegedi, A.; Mihaly, J. [Institute of Nanochemistry and Catalysis, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út. 59-67, 1025 Budapest (Hungary); Tzankov, B.; Lambov, N.; Konstantinov, S.; Tzankova, V. [Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia (Bulgaria); Pessina, F.; Valoti, M. [Dipartimento di Scienze della Vita, Universita di Siena, via Aldo Moro 2, Siena (Italy)

    2014-03-15

    Non-functionalized and amino-functionalized mesoporous silica nanoparticle were loaded with anti-inflammatory drug budesonide and additionally post-coated with bioadhesive polymer (carbopol). TEM images showed spherical shape of the nanoparticles and slightly higher polydispersity after coating with carbopol. Nitrogen physisorption and thermogravimetic analysis revealed that more efficient loading and incorporation into the pores of nanoparticles was achieved with the amino-functionalized silica carrier. Infrared spectra indicated that the post-coating of these nanoparticles with carbopol led to the formation of bond between amino groups of the functionalized carrier and carboxyl groups of carbopol. The combination of amino-functionalization of the carrier with the post-coating of the nanoparticles sustained budesonide release. Further, an in vitro model of inflammatory bowel disease showed that the cytoprotective effect of budesonide loaded in the post-coated silica nanoparticles on damaged HT-29 cells was more pronounced compared to the cytoprotection obtained with pure budesonide. -- Graphical abstract: Silica mesoporous MCM-41 particles were amino-functionalized, loaded with budesonide and post-coated with bioadhesive polymer (carbopol) in order to achieve prolonged residence of anti-inflammatory drug in GIT. Highlights: • Higher drug loading in amino-functionalized mesoporous silica. • Amino-functionalization and post-coating of the nanoparticles sustained drug release. • Achievement of higher cytoprotective effect with drug loaded into the nanoparticles.

  5. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

    Science.gov (United States)

    Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2009-12-23

    Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

  6. Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death.

    Science.gov (United States)

    Tu, Zhi-Shan; Wang, Qi; Sun, Dan-Dan; Dai, Fang; Zhou, Bo

    2017-07-07

    Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic o-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Atorvastatin Downregulates In Vitro Methyl Methanesulfonate and Cyclophosphamide Alkylation-Mediated Cellular and DNA Injuries

    Directory of Open Access Journals (Sweden)

    Carlos F. Araujo-Lima

    2018-01-01

    Full Text Available Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase inhibitors, and this class of drugs has been studied as protective agents against DNA damages. Alkylating agents (AAs are able to induce alkylation in macromolecules, causing DNA damage, as DNA methylation. Our objective was to evaluate atorvastatin (AVA antimutagenic, cytoprotective, and antigenotoxic potentials against DNA lesions caused by AA. AVA chemopreventive ability was evaluated using antimutagenicity assays (Salmonella/microsome assay, cytotoxicity, cell cycle, and genotoxicity assays in HepG2 cells. The cells were cotreated with AVA and the AA methyl methanesulfonate (MMS or cyclophosphamide (CPA. Our datum showed that AVA reduces the alkylation-mediated DNA damage in different in vitro experimental models. Cytoprotection of AVA at low doses (0.1–1.0 μM was observed after 24 h of cotreatment with MMS or CPA at their LC50, causing an increase in HepG2 survival rates. After all, AVA at 10 μM and 25 μM had decreased effect in micronucleus formation in HepG2 cells and restored cell cycle alterations induced by MMS and CPA. This study supports the hypothesis that statins can be chemopreventive agents, acting as antimutagenic, antigenotoxic, and cytoprotective components, specifically against alkylating agents of DNA.

  8. Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response.

    Science.gov (United States)

    Adin, Christopher A; VanGundy, Zachary C; Papenfuss, Tracey L; Xu, Feng; Ghanem, Mostafa; Lakey, Jonathan; Hadley, Gregg A

    2017-01-24

    Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen-presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1β and IL-6), and chemokines (MCP-1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation.

  9. Nitric oxide protects macrophages from hydrogen peroxide-induced apoptosis by inducing the formation of catalase.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Kitao, Tatsuya; Kishino, Takashi; Yamamuro, Akiko; Maeda, Sadaaki

    2006-04-15

    We investigated the cytoprotective effect of NO on H2O2-induced cell death in mouse macrophage-like cell line RAW264. H2O2-treated cells showed apoptotic features, such as activation of caspase-9 and caspase-3, nuclear fragmentation, and DNA fragmentation. These apoptotic features were significantly inhibited by pretreatment for 24 h with NO donors, sodium nitroprusside and 1-hydroxy-2-oxo-3,3-bis-(2-aminoethyl)-1-triazene, at a low nontoxic concentration. The cytoprotective effect of NO was abrogated by the catalase inhibitor 3-amino-1,2,4-triazole but was not affected by a glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine. NO donors increased the level of catalase and its activity in a concentration-dependent manner. Cycloheximide, a protein synthesis inhibitor, inhibited both the NO-induced increase in the catalase level and the cytoprotective effect of NO. These results indicate that NO at a low concentration protects macrophages from H2O2-induced apoptosis by inducing the production of catalase.

  10. Red Chicory (Cichorium intybus L. cultivar as a Potential Source of Antioxidant Anthocyanins for Intestinal Health

    Directory of Open Access Journals (Sweden)

    Laura D'evoli

    2013-01-01

    Full Text Available Fruit- and vegetable-derived foods have become a very significant source of nutraceutical phytochemicals. Among vegetables, red chicory (Cichorium Intybus L. cultivar has gained attention for its content of phenolic compounds, such as the anthocyanins. In this study, we evaluated the nutraceutical effects, in terms of antioxidant, cytoprotective, and antiproliferative activities, of extracts of the whole leaf or only the red part of the leaf of Treviso red chicory (a typical Italian red leafy plant in various intestinal models, such as Caco-2 cells, differentiated in normal intestinal epithelia and undifferentiated Caco-2 cells. The results show that the whole leaf of red chicory can represent a good source of phytochemicals in terms of total phenolics and anthocyanins as well as the ability of these phytochemicals to exert antioxidant and cytoprotective effects in differentiated Caco-2 cells and antiproliferative effects in undifferentiated Caco-2 cells. Interestingly, compared to red chicory whole leaf extracts, the red part of leaf extracts had a significantly higher content of both total phenolics and anthocyanins. The same extracts effectively corresponded to an increase of antioxidant, cytoprotective, and antiproliferative activities. Taken together, these findings suggest that the red part of the leaf of Treviso red chicory with a high content of antioxidant anthocyanins could be interesting for development of new food supplements to improve intestinal health.

  11. Nitric oxide protects anterior pituitary cells from cadmium-induced apoptosis.

    Science.gov (United States)

    Poliandri, Ariel H B; Velardez, Miguel O; Cabilla, Jimena P; Bodo, Cristian C A; Machiavelli, Leticia I; Quinteros, Alnilan F; Duvilanski, Beatriz H

    2004-11-01

    Cadmium (Cd2+) is a potent toxic metal for both plants and animals. Chronic exposure to low doses of Cd2+ results in damage to several organs. We have previously reported that Cd2+ induces apoptosis in anterior pituitary cells by a caspase- and oxidative stress-dependent mechanism. Nitric oxide (NO) synthesis is affected by Cd2+ in several systems. NO has been shown to be either cytoprotective or cytotoxic in many systems. The aim of this study was to evaluate the possible participation of NO in the cytotoxic effect of Cd2+ on rat anterior pituitary cells. Cell viability was evaluated by mitochondrial dehydrogenase activity assay and confirmed by microscopy, studying nuclear morphology. Here we show that DETA NONOate ((Z)-1-[2 (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate), a long-term NO donor, at concentrations below 0.5 mM, reduces nuclear condensation and fragmentation and reverses the decrease in cellular activity induced by Cd2+. Cd2+, by itself, induced NO synthesis, and inhibition of this synthesis enhanced Cd2+ cytotoxicity. NO also prevented caspase-3 activation and lipidic peroxidation induced by Cd2+. The NO/cGMP pathway does not seem to be involved in the cytoprotective effect of NO. These results indicate that NO has a cytoprotective role in Cd2+ -induced apoptosis, suggesting that endogenous NO could have a physiological role in protecting anterior pituitary cells.

  12. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    International Nuclear Information System (INIS)

    Guo, Tai L.; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

    2014-01-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  13. Attenuation of Aβ{sub 25–35}-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangbao; Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Guibo, E-mail: sunguibo@126.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Ye, Jingxue [Jilin Agricultural University, Changchun, Jilin 130021 (China); Zhou, Yanhui [Center of Cardiology, People' s Hospital of Jilin Province, Changchun, 130021, Jilin (China); Dong, Xi [Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Wang, Tingting; Lu, Shan [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Xiaobo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China)

    2014-08-15

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ{sub 25–35}-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ{sub 25–35} (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ{sub 25–35} treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ{sub 25–35} treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ{sub 25–35}-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ{sub 25–35}-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens

  14. Attenuation of Aβ25–35-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    International Nuclear Information System (INIS)

    Meng, Xiangbao; Wang, Min; Sun, Guibo; Ye, Jingxue; Zhou, Yanhui; Dong, Xi; Wang, Tingting; Lu, Shan; Sun, Xiaobo

    2014-01-01

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ 25–35 -induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ 25–35 (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ 25–35 treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ 25–35 treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ 25–35 -induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ 25–35 -induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens or gypenosides

  15. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  16. The position of prenylation of isoflavonoids and stilbenoids from legumes (Fabaceae) modulates the antimicrobial activity against Gram positive pathogens.

    Science.gov (United States)

    Araya-Cloutier, Carla; den Besten, Heidy M W; Aisyah, Siti; Gruppen, Harry; Vincken, Jean-Paul

    2017-07-01

    The legume plant family (Fabaceae) is a potential source of antimicrobial phytochemicals. Molecular diversity in phytochemicals of legume extracts was enhanced by germination and fungal elicitation of seven legume species, as established by RP-UHPLC-UV-MS. The relationship between phytochemical composition, including different types of skeletons and substitutions, and antibacterial properties of extracts was investigated. Extracts rich in prenylated isoflavonoids and stilbenoids showed potent antibacterial activity against Listeria monocytogenes and methicillin-resistant Staphylococcus aureus at concentrations between 0.05 and 0.1% (w/v). Prenylated phenolic compounds were significantly (p<0.01) correlated with the antibacterial properties of the extracts. Furthermore, the position of the prenyl group within the phenolic skeleton also influenced the antibacterial activity. Overall, prenylated phenolics from legume seedlings can serve multiple purposes, e.g. as phytoestrogens they can provide health benefits and as natural antimicrobials they offer preservation of foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Investigation of de novo cholesterol synthetic capacity in the gonads of goldfish (Carassius auratus exposed to the phytosterol beta-sitosterol

    Directory of Open Access Journals (Sweden)

    MacLatchy Deborah L

    2006-11-01

    Full Text Available Abstract Total and intra-mitochondrial gonadal cholesterol concentrations are decreased in fish exposed to the phytoestrogen beta-sitosterol (beta-sit. The present study examined the potential for beta-sit to disrupt de novo cholesterol synthesis in the gonads of goldfish exposed to 200 microgram/g beta-sit and 10 microgram/g 17beta-estradiol (E2; estrogenic control by intra-peritoneal Silastic® implants for 21 days. The de novo cholesterol synthetic capacity was estimated by incubating gonadal tissue with 14C-acetate for a period of 18 hours, followed by chloroform/methanol lipid extraction and thin layer chromatography (TLC lipid separation. Lipid classes were confirmed using infrared spectroscopy. Plasma testosterone (T and total cholesterol concentration were measured and gonadosomatic index (GSI was calculated. Plasma T was significantly reduced in male beta-sit-treated fish compared to control and E2-treated fish (p

  18. Review of Efficacy of Complementary and Alternative Medicine Treatments for Menopausal Symptoms.

    Science.gov (United States)

    Moore, Thea R; Franks, Rachel B; Fox, Carol

    2017-05-01

    Complementary and alternative medicine (CAM) treatments have been used for thousands of years around the world. There has been increased interest in utilizing CAM for menopausal symptoms since the release of results of the Women's Health Initiative elucidated long-term adverse effects associated with hormone therapy. Women looking for more natural or safer means to treat hot flushes, night sweats, and other menopausal symptoms often turn to CAM such as yoga, phytoestrogens, or black cohosh. Yet there have been few well-conducted studies looking at the efficacy of these treatments. This review examines randomized clinical trials, systematic reviews, and meta-analyses evaluating the effectiveness of commonly used CAM for the treatment of menopausal symptoms. © 2017 by the American College of Nurse-Midwives.

  19. Epidemiologic Studies of Isoflavones & Mammographic Density

    Science.gov (United States)

    Maskarinec, Gertraud; Verheus, Martijn; Tice, Jeffrey A.

    2010-01-01

    Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density. PMID:22253990

  20. Epidemiologic Studies of Isoflavones & Mammographic Density

    Directory of Open Access Journals (Sweden)

    Jeffrey A. Tice

    2010-01-01

    Full Text Available Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density.

  1. Endocrine Disruptors and Leydig Cell Function

    Directory of Open Access Journals (Sweden)

    K. Svechnikov

    2010-01-01

    Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  2. Impact of xanthohumol (a prenylated flavonoid from hops) on DNA stability and other health-related biochemical parameters

    DEFF Research Database (Denmark)

    Ferk, Franziska; Mišík, Miroslav; Nersesyan, Armen

    2016-01-01

    SCOPE: Xanthohumol (XN) is a hop flavonoid found in beers and refreshment drinks. Results of in vitro and animal studies indicate that it causes beneficial health effects due to DNA protective, anti-inflammatory, antioxidant, and phytoestrogenic properties. Aim of the present study was to find out...... if XN causes alterations of health-related parameters in humans. METHODS AND RESULTS: The effects of the flavonoid were investigated in a randomized crossover intervention trial (n = 22) in which the participants consumed a XN drink (12 mg XN/P/day). We monitored alterations of the DNA stability......'-deoxyguanosine and 8-oxo-guanosine in urine was reduced. The assumption that the flavonoid causes DNA protection was confirmed in a randomized follow-up study with pure XN (n = 10) with a parallel design. Other biochemical parameters reflecting the redox- and hormonal status and lipid- and glucose metabolism...

  3. Seasonal and sex-related variations in serum steroid hormone levels in wild and farmed brown trout Salmo trutta L. in the north-west of Spain.

    Science.gov (United States)

    Fregeneda-Grandes, Juan M; Hernández-Navarro, Salvador; Fernandez-Coppel, Ignacio A; Correa-Guimaraes, Adriana; Ruíz-Potosme, Norlan; Navas-Gracia, Luis M; Aller-Gancedo, J Miguel; Martín-Gil, Francisco J; Martín-Gil, Jesús

    2013-12-01

    Serum steroid profiles were investigated in order to evaluate the potential use of circulating sex steroid levels as a tool for sex identification in brown trout. Changes in the serum concentrations of testosterone (T), progesterone (P), 17-β-estradiol (E2), and cortisol (F) in wild and farmed mature female and male brown trout, Salmo trutta L., were measured in each season (January, May, July, and October) in six rivers and four hatcheries located in the north-west of Spain. Serum cortisol levels in farmed brown trout were significantly higher and showed a seasonal pattern opposite to that found in wild trout. Because levels of the hormones under study can be affected by disruptive factors such as exposure to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary-adrenal axis), both factors are taken into account.

  4. PHYTOCHEMICAL ASSESSMENT ON N-HEXANE EXTRACT AND FRACTIONS OF Marsilea crenata Presl. LEAVES THROUGH GC-MS

    Directory of Open Access Journals (Sweden)

    Burhan Ma'arif

    2016-08-01

    Full Text Available Estrogen deficiency causes various health problems in postmenopausal women, including osteoporosis. Phytoestrogen emerged as a potential alternative of estrogen with minimum side effects. Green clover (Marsilea crenata Presl. is a typical plant in East Java which suspected contains estrogen-like substances. The aim of this research was to report the phytochemical properties of M. crenata using GC-MS as a preliminary study. M. crenata leaves were dried and extracted with n-hexane, then separated using vacuum column chromatography to get four fractions, after that the n-hexane extract and four fractions were identified with GC-MS. The results of GC-MS analysis showed some compounds contained in M. crenata leaves like monoterpenoid, diterpenoid, fatty acid compounds, and other unknown compounds. The results obtained in this research indicated a promising potential of M. crenata as medicinal plants, especially as antiosteoporotic agent.

  5. [Plants as a source of natural harmful substances].

    Science.gov (United States)

    Czerwiecki, Ludwik

    2005-01-01

    In this review the several data concerning phytotoxins as natural harmful substances of plants and phycotoxins--toxicants of algae were described. For example plants are source of pyrrolizidine alkaloids, glycoalkaloids, glucosinolates as well as glycosides, saponine and psolarens. Possible adverse effects of phytoestrogens as endocrine disruptors versus beneficial influence these substances on human organism were mentioned. About lectins as possible factors of some diseases was reported, as well as some proteins as allergens of soy and peanuts was mentioned. Accumulated by shellfish and fish the most important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and ciguatoxins were described. Phycotoxins produced several poisoning symptoms. Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was mentioned. In conclusion, the need of limitation of permissible levels of some plant toxicants, development of analytical methods as well as knowledge of influence of some technological processes on toxic plant substances was highlighted. The importance of balanced diet as a tool of defense against plant toxicants was concluded.

  6. 8-Prenylnaringenin from hop (Humulus lupulus L. – a panacea for menopause?

    Directory of Open Access Journals (Sweden)

    Minecka Aldona

    2017-12-01

    Full Text Available 8-Prenylnaryngenin (8-PN is the strongest known phytoestrogen (PE. Its main source is the female inflorescences of hops (Humulus lupulus L.. 8-PN, which, in contrast to other PEs, is proven to have stronger activity and higher affinity for the α subtype of estrogen receptor (ER. Therefore, it may be an effective substitute for hormone replacement therapy (HRT. The studies in postmenopausal women have shown its particular effectiveness in reducing hot flashes. However, a strong stimulation of uterus by 8-PN may be associated with the occurrence of adverse effects (eg. bleeding and increase the risk of carcinogenesis. The H. lupulus extracts preparations are currently supplements which makes control of the doses used and thus increases the occurrence of uncontrolled self-treatment difficult. This paper presents the current knowledge on 8-PN and discusses the potential risks associated with use of hops to alleviate the symptoms of menopause.

  7. Endocrine Disruption of Vasopressin Systems and Related Behaviors

    Directory of Open Access Journals (Sweden)

    Heather B. Patisaul

    2017-06-01

    Full Text Available Endocrine disrupting chemicals (EDCs are chemicals that interfere with the organizational or activational effects of hormones. Although the vast majority of the EDC literature focuses on steroid hormone signaling related impacts, growing evidence from a myriad of species reveals that the nonapeptide hormones vasopressin (AVP and oxytocin (OT may also be EDC targets. EDCs shown to alter pathways and behaviors coordinated by AVP and/or OT include the plastics component bisphenol A (BPA, the soy phytoestrogen genistein (GEN, and various flame retardants. Many effects are sex specific and likely involve action at nuclear estrogen receptors. Effects include the elimination or reversal of well-characterized sexually dimorphic aspects of the AVP system, including innervation of the lateral septum and other brain regions critical for social and other non-reproductive behaviors. Disruption of magnocellular AVP function has also been reported in rats, suggesting possible effects on hemodynamics and cardiovascular function.

  8. A hypothesis regarding the molecular mechanism underlying dietary soy-induced effects on seizure propensity.

    Directory of Open Access Journals (Sweden)

    Cara Jean Westmark

    2014-09-01

    Full Text Available Numerous neurological disorders including fragile X syndrome, Down syndrome, autism and Alzheimer’s disease are comorbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

  9. Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

    DEFF Research Database (Denmark)

    Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

    2003-01-01

    arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

  10. Edible seeds from Cucurbitaceae family as potential functional foods: Immense promises, few concerns.

    Science.gov (United States)

    Patel, Seema; Rauf, Abdur

    2017-07-01

    Cucurbitaceae family members such as pumpkin and watermelon have seeds that are discarded as the by-products of food processing. However, they have been discovered to contain a rich repertoire of nutrients such as proteins, unsaturated fatty acids, phenolic acids, carotenoids, tocopherol, phytosterol, squalene etc. Biological assays have proven the seed extracts to exert antioxidative, hypoglycemic, anticancer, antihypertensive, cardioprotective, antilipemic, gynoprotective, and anthelmintic properties. Further, the seeds do not contain any major anti-nutrients. Phytoestrogens like β-sitosterol occur, which might be acting as agonists or antagonists of estrogen and testosterone, given their validated role in gyenic and prostate health. Few instances of intestinal bezoar, and allergy, following pumpkin seeds consumption have emerged. After the risk-benefit analysis though exhaustive literature search, it can be suggested that these seeds are underutilized and they can be used to formulate a myriad of nutraceuticals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

    Science.gov (United States)

    Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

    2010-03-01

    Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

  12. 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ronghe, Amruta; Chatterjee, Anwesha [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States); Singh, Bhupendra [Department of Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Dandawate, Prasad [ISTRA, Department of Chemistry, Abeda Inamdar Senior College, University of Pune (India); Abdalla, Fatma; Bhat, Nimee K. [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States); Padhye, Subhash [ISTRA, Department of Chemistry, Abeda Inamdar Senior College, University of Pune (India); Bhat, Hari K., E-mail: bhath@umkc.edu [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States)

    2016-06-15

    Breast cancer is a public health concern worldwide. Prolonged exposure to estrogens has been implicated in the development of breast neoplasms. Epidemiologic and experimental evidence suggest a chemopreventive role of phytoestrogens in breast cancers. Resveratrol, a naturally occurring phytoestrogen, has been shown to have potent anti-cancer properties. However, poor efficacy and bioavailability have prevented the use of resveratrol in clinics. In order to address these problems, we have synthesized a combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the proliferation of breast cancer cells. We have recently shown that 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), has better anti-cancer properties than resveratrol and any other resveratrol analog we have synthesized so far. The objective of this study was to investigate the regulation of estrogen receptors (ERs) α and β by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERβ and inhibits that of ERα. TIMBD inhibits mRNA and protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, which are important regulators of cellular proliferation. TIMBD significantly induces protein expression levels of tumor suppressor genes p53 and p21 in MCF-7 cells. TIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10 A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERβ plays a partial role in inhibition of proliferation by TIMBD while ERα overexpression does not significantly affect TIMBD's inhibition. - Highlights: • Resveratrol analog TIMBD inhibits growth of breast cancer cells. • TIMBD induces protein expression levels of ERβ and inhibits that of ERα. • TIMBD inhibits c-Myc and cyclin D1, and induces p53 and p21. • TIMBD suppresses c-Myc in an ER-dependent fashion.

  13. 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells

    International Nuclear Information System (INIS)

    Ronghe, Amruta; Chatterjee, Anwesha; Singh, Bhupendra; Dandawate, Prasad; Abdalla, Fatma; Bhat, Nimee K.; Padhye, Subhash; Bhat, Hari K.

    2016-01-01

    Breast cancer is a public health concern worldwide. Prolonged exposure to estrogens has been implicated in the development of breast neoplasms. Epidemiologic and experimental evidence suggest a chemopreventive role of phytoestrogens in breast cancers. Resveratrol, a naturally occurring phytoestrogen, has been shown to have potent anti-cancer properties. However, poor efficacy and bioavailability have prevented the use of resveratrol in clinics. In order to address these problems, we have synthesized a combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the proliferation of breast cancer cells. We have recently shown that 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), has better anti-cancer properties than resveratrol and any other resveratrol analog we have synthesized so far. The objective of this study was to investigate the regulation of estrogen receptors (ERs) α and β by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERβ and inhibits that of ERα. TIMBD inhibits mRNA and protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, which are important regulators of cellular proliferation. TIMBD significantly induces protein expression levels of tumor suppressor genes p53 and p21 in MCF-7 cells. TIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10 A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERβ plays a partial role in inhibition of proliferation by TIMBD while ERα overexpression does not significantly affect TIMBD's inhibition. - Highlights: • Resveratrol analog TIMBD inhibits growth of breast cancer cells. • TIMBD induces protein expression levels of ERβ and inhibits that of ERα. • TIMBD inhibits c-Myc and cyclin D1, and induces p53 and p21. • TIMBD suppresses c-Myc in an ER-dependent fashion.

  14. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yue; Zhang, Shunfen [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Zhou, Tianyan [Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083 (China); Huang, Chaoqun; McLaughlin, Alicia [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Chen, Guangping, E-mail: guangping.chen@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States)

    2013-04-15

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ► Liver X receptor α mediated genistein induction of hSULT2A1 in Hep G2 cells. ► LXRα and RXRα dimerization further activated this induction. ► Western blot results agreed well with luciferase reporter gene assay results. ► LXRs gene silencing significantly decreased hSULT2A1 expression. ► ChIP analysis suggested that genistein enhances hLXRα binding to the hSULT2A1 promoter.

  15. The anti-cancer charm of flavonoids: a cup-of-tea will do!

    Science.gov (United States)

    Amin, Amr; Buratovich, Michael

    2007-06-01

    Hormone-dependent cancers of the breast, prostate and colon have, in the past decade, become the leading causes of morbidity and mortality. Billions of dollars have been, and still are being spent to study cancers like these, and, in the past three decades, thanks to work by thousands of dedicated scientists, tremendous advancements in the understanding and treatment of cancer have been made. Nevertheless, as there is no sure-fire cure for a variety of cancers to date, natural protection against cancer has been receiving a great deal of attention lately not only from cancer patients but, surprisingly, from physicians as well. Phytoestrogens, plant-derived secondary metabolites, are diphenolic substances with structural similarity to naturally-occurring human steroid hormones. Phytoestrogens are normally divided into three main classes: flavonoids, coumestans and lignans. Flavonoids are found in almost all plant families in the leaves, stems, roots, flowers and seeds of plants and are among the most popular anti-cancer candidates. Flavonoidic derivatives have a wide range of biological actions such as antibacterial, antiviral, anti-inflammatory, anticancer, and antiallergic activities. Some of these benefits are explained by the potent antioxidant effects of flavonoids, which include metal chelation and free-radical scavenging activities. Patent applications regarding flavonoids range from protocols for extraction and purification from natural resources and the establishment of various biological activities for these extracts to novel methods for the production and isolation of flavonoids with known biological activities. This review will bring the reader up to date on the current knowledge and research available in the field of flavonoids and hormone-dependent cancers, and many of the submitted patents that exploit flavonoids.

  16. Effect of resveratrol on 17beta-estradiol sulfation by human hepatic and jejunal S9 and recombinant sulfotransferase 1E1.

    Science.gov (United States)

    Furimsky, Anna M; Green, Carol E; Sharp, Lewanne E Hunt; Catz, Paul; Adjei, Araba A; Parman, Toufan; Kapetanovic, Izet M; Weinshilboum, Richard M; Iyer, Lalitha V

    2008-01-01

    The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 microM) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1.

  17. In Vitro Fermentative Production of Plant Lignans from Cereal Products in Relationship with Constituents of Non-Starch Polysaccharides

    Directory of Open Access Journals (Sweden)

    Elena Bartkiene

    2012-01-01

    Full Text Available Recently special attention has been paid to dietary fibre-associated phytoestrogens such as plant lignans, which are related to the prevention of different hormone-dependent diseases. Therefore, phytoestrogens associated with dietary fibre and their metabolites are of interest for investigation. The aim of this work is to investigate the formation of enterolignans: enterolactone (ENL and enterodiol (END from their precursors by the action of intestinal microflora and their relationship with non-starch polysaccharides (NSP in various cereal products from wheat, rye, barley and oats. For the investigation of the bioconversion of plant lignans, a technique of in vitro fermentation was used and the quantitative analysis of their metabolites ENL and END was performed by high-performance liquid chromatography (HPLC with coulometric electrode array detection. The enterolignan formation in various cereal products ranged from 78.3 to 321.9 nmol/g depending on the product type: END from 8.7 to 149.3 nmol/g and ENL from 64.4 to 278.3 nmol/g. The lignan production in bran was about two times higher than that in whole flour of the same kind of cereals. Close correlations were found between the total NSP content and the total amount of enterolignans and ENL; between pentoses and the total amount of enterolignans and ENL; between arabinose or xylose and ENL; and between galactose and END values. Considering the correlations between hexoses and END as well as between pentoses and ENL found in cereals, it can be assumed that pentoses are closely related to the quantities of plant lignans in cereal products and their conversion to enterolignans.

  18. Estrogen hormone level of prepubertal female rat treated with Calliandra calothyrsus ethanolic leaf extract

    Science.gov (United States)

    Setyawati, I.; Wiratmini, N. I.; Narayani, I.

    2018-03-01

    This research examined the phytoestrogen potential of Calliandra calothyrsus leaf extract in prepubertal female rat (Rattus norvegicus). Sixty weaned female rats (21 days old) were divided into five groups i.e. control (K), negative control which was given 0.5% Na CMC suspension (KN) and treatment groups which were given with C. calothyrsus ethanolic leaf extract doses 25 mg/kg bw (P1), 50 mg/kg bw (P2) and 75 mg/kg bw (P3). The treatment suspension was administered 0.5 mL/rat/day by gavage for 28 days, started at the age of 21st days old. The rats were sacrificed and the blood samples were collected from 4 rats / group at the age of 28th, 42nd and 56th days old, each. The concentration of estrogen hormone levels were measured from blood serum by ELISA kit and were read at 450 nm wavelength with an ELISA Spectrophotometer. Data was analyzed statistically by General Linear Model with 95% of confidence. The result showed that rat’s body weight decreased significantly with the higher doses and the longer the treatment of C. calothyrsus leaf extract due to the anti-nutritive activity of calliandra tannins. The estrogen hormone level was significantly increased at the highest dose. The highest estrogen levels were found in the group of female rats which were given the exctract of 75 mg/kg bw until the age of 42nd days. This results showed that there was a phytoestrogen potential in the C. calothyrsus leaf extract.

  19. Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

    2017-06-15

    Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

  20. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    International Nuclear Information System (INIS)

    Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko

    2011-01-01

    Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  1. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsukura, Hiroshi, E-mail: hmatsukura.epi@mri.tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: nsato.epi@tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)

    2011-08-26

    Highlights: {yields} Genistein (GEN) is a phytoestrogen found in soy products. {yields} GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. {yields} GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. {yields} A high-resolution melting assay was used to screen for epigenetic change. {yields} We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  2. Wpływ estrogenów na stężenie N-terminalnego propeptydu kolagenu typu I w płynie uzyskanym z przestrzennych hodowli ludzkich fibroblastów powięzi łonowo-cewkowej prowadzonych na siatkach polipropylenowych stosowanych w uroginekologii operacyjnej

    Directory of Open Access Journals (Sweden)

    Jacek Tomaszewski

    2010-02-01

    Full Text Available Objectives: Polypropylene meshes are widely used for surgical treatment of stress urinary incontinence(SUI and pelvic organ prolapse (POP. Synthesis and deposition of collagen induced by an inserted implant arelargely controlled by oestrogens. The aim of the study was to assess the rate of collagen type I (Col I synthesisby pubo-cervical fascia (PCF fibroblasts cultured with mono- or multifilament polypropylene meshes in thepresence of oestrogens. Material and Methods: Specimens of PCF were obtained during a surgical procedure from a 56-year-old womansuffering from SUI and POP. Fibroblasts were cultured with mono- or multifilament meshes and exposed to17β-oestradiol, oestriol or phytoestrogen daidzein. The cultures were run for 216 hrs and the media were replaced every 72 hrs. Procollagen type 1 N-terminal propeptide (PINP, a marker of Col I biosynthesis, was assessedin culture media by radioimmunoassay. Results: The biosynthesis of Col I was more abundant in the presence of monofilament than multifilamentmeshes. Fibroblasts exposed to oestriol or daidzein produced more Col I than those treated with oestradiol,regardless of the mesh applied. In the presence of monofilament mesh the rate of Col I synthesis induced byoestriol and daidzein increased persistently until the end of the experiment, whereas the peak concentration ofPINP in cultures treated with oestradiol was observed between 72 hrs and 144 hrs. In the presence of multifilamentmesh the rate of Col I production dropped after 144 hrs in all cultures. Conclusions: PCF fibroblasts produce more Col I when cultured on monofilament than on multifilamentmesh. This process may be enhanced by oestriol and phytoestrogens.

  3. Evaluation of estrogenic potential of flavonoids using a recombinant yeast strain and MCF7/BUS cell proliferation assay.

    Directory of Open Access Journals (Sweden)

    Flávia A Resende

    Full Text Available Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. Furthermore, there is a search for compounds with estrogenic activity that can replace estrogen in hormone replacement therapy during menopause, without the undesirable effects of estrogen, such as the elevation of breast cancer occurrence. Thus, the principal objective of this study was to assess the estrogenic activity of flavonoids with different hydroxylation patterns: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone via two different in vitro assays, the recombinant yeast assay (RYA and the MCF-7 proliferation assay (E-screen, since the most potent phytoestrogens are members of the flavonoid family. In these assays, kaempferol was the only compound that showed ERα-dependent transcriptional activation activity by RYA, showing 6.74±1.7 nM EEQ, besides acting as a full agonist for the stimulation of proliferation of MCF-7/BUS cells. The other compounds did not show detectable levels of interaction with ER under the conditions used in the RYA. However, in the E-screen assay, compounds such as galangin, luteolin and fisetin also stimulated the proliferation of MCF-7/BUS cells, acting as partial agonists. In the evaluation of antiestrogenicity, the compounds quercetin, chrysin and 3-hydroxyflavone significantly inhibited the cell proliferation induced by 17-β-estradiol in the E-screen assay, indicating that these compounds may act as estrogen receptor antagonists. Overall, it became clear in the assay results that the estrogenic activity of flavonoids was affected by small structural differences such as the number of hydroxyl groups, especially those on the B ring of the flavonoid.

  4. Soy-isoflavone supplementation tends to reduce menopausal symptoms in postmenopausal women

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    Raditya Wratsangka

    2013-08-01

    Full Text Available Background Menopausal symptoms in postmenopausal women tend to decrease health-related quality of life (HRQoL. The present study’s objective was to determine the effect of daily supplementation of 100 mg soy isoflavones on menopausal symptoms of healthy postmenopausal women. Isoflavones are phytoestrogens abundantly found in soy beans, and several studies have demonstrated that isoflavones are the best among the phytoestrogens. Methods The study was a community-based double blind randomized controlled trial involving 60 healthy postmenopausal women, aged between 48–60 years, in the Mampang Prapatan District, South Jakarta. Participants were block-randomized to receive either 100 mg soy-isoflavone + 500 mg calcium carbonate (intervention group or 500 mg calcium carbonate only (control group. Both supplements were taken daily for 12 weeks, from January to April 2010. Menopausal symptoms (measured by Menopause Rating Scale questionnaire were assessed at baseline and after supplementation. Chi-square test was used to examine the effect of soy isoflavone supplementation on menopausal symptoms. Results Fifty-six (93.3% of participants completed the study. There were no statistically significant differences (p>0.05 in the prevalence of menopausal symptoms between the isoflavone group and the control group. However, supplementation of soy isoflavones for 12 weeks tended to decrease the prevalence of menopausal symptoms in women with normal body mass index and adequate daily dietary isoflavone intake. Conclusion Daily supplementation of 100 mg soy isoflavones for 12 weeks tend to decrease the incidence of menopausal symptoms in postmenopausal women.

  5. The morpho-functional parameters of rat pituitary hormone producing cells after genistein treatment

    Directory of Open Access Journals (Sweden)

    Svetlana Trifunović

    2018-03-01

    Full Text Available Phytoestrogens are a diverse group of steroid–like compounds that occur naturally in many plants. There are various types of phytoestrogens, including the best-researched isoflavones which are commonly found in soy. The consumption of soy products has many health benefits, including protection against breast cancer, prostate cancer, menopausal symptoms, heart disease and osteoporosis. In contrast, use of hormonally active compounds-isoflavones may unfortunately interfere with the endocrine system and can have far-reaching consequences. Genistein, the most abundant soy-bean derived isoflavone, possesses a ring system similar to estrogens and acts through an estrogen receptor (ER-mediated mechanism, by increasing or decreasing the transcription of ER-dependent target genes. Also, genistein can act on cells through ER non-dependent mechanisms, such as tyrosine kinase inhibitor. The neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, and stress responsiveness. It is well known, that estrogen is important for development of the neuroendocrine system in both sexes. At the pituitary level, estrogen is known to affect the regulation of all hormone producing (HP cells, by direct and/or indirect mechanisms. Due to structural and functional resemblance to estrogen, the question may arise of whether and how genistein affects the morphofunctional features of pituitary HP cells. This review deals with the consequences of genistein’s effects on morphological, stereological and hormonal features of HP cells within the anterior pituitary gland. Transparency on this issue is needed because isoflavones are presently highly consumed. Inter alia, genistein as well as other isoflavones, are present in various dietary supplements and generally promoted as an accepted alternative to estrogen replacement therapy. Potential isoflavone biomedical exploitation is not

  6. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  7. Dietary estrogens--a probable cause of infertility and liver disease in captive cheetahs.

    Science.gov (United States)

    Setchell, K D; Gosselin, S J; Welsh, M B; Johnston, J O; Balistreri, W F; Kramer, L W; Dresser, B L; Tarr, M J

    1987-08-01

    The cheetah in the wild is "racing towards extinction" mostly due to habitat destruction. Its survival will probably depend on accelerated captive breeding. At this time, however, reproductive failure and liver disease threaten the future of the captive cheetah population. Histopathological evaluation of more than 100 cheetah livers identified venocclusive disease as the main hepatic lesion responsible for liver disease in this species. Analysis of the commercial feline diet by high-performance liquid chromatography and gas-liquid chromatography-mass spectrometry revealed large amounts of two phytoestrogens identified as daidzein and genistein. These compounds were found to be derived from a soybean product that was a component of the cheetah diet, and their concentrations both ranged from 18 to 35 micrograms/g diet. The adult cheetah consequently consumes approximately 50 mg/day of these weak estrogens. When extracts of the diet were tested for estrogenicity using a bioassay, a dose-related increase in uterine weight was observed. In 4 cheetahs studied, withdrawal of this feline diet by substitution with a chicken diet resulted in an improvement in conventional liver function tests and a normalization in the appearance of hepatic mitochondria. We conclude that the relatively high concentrations of phytoestrogens from soybean protein present in the commercial diet fed to captive cheetahs in North American zoos may be one of the major factors in the decline of fertility and in the etiology of liver disease in this species. The survival of the captive cheetah population could depend upon a simple change of diet by excluding exogenous estrogen.

  8. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    International Nuclear Information System (INIS)

    Patel, Shreya; Peretz, Jackye; Pan, Yua