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Find video protocols related to scientific articles indexed in Pubmed.
Nocturnal light exposure alters hepatic Pai-1 expression by stimulating the adrenal pathway in C3H mice.
Exp. Anim.
PUBLISHED: 08-01-2014
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Recent studies have suggested the possibility that nocturnal light exposure affects many biological processes in rodents, especially the circadian rhythm, an endogenous oscillation of approximately 24 h. However, there is still insufficient information about the physiological effects of nocturnal light exposure. In this study, we examined the changes in gene expression and serum levels of plasminogen activator inhibitor-1 (PAI-1), a major component of the fibrinolytic system that shows typical circadian rhythmicity, in C3H/He mice. Zeitgeber time (ZT) was assessed with reference to the onset of light period (ZT0). Exposure to fluorescent light (70 lux) for 1 h in the dark period (ZT14) caused a significant increase in hepatic Pai-1 gene expression at ZT16. Serum PAI-1 levels also tended to increase, albeit not significantly. Expression levels of the typical clock genes Bmal1, Clock, and Per1 were significantly increased at ZT21, ZT16, and ZT18, respectively. Exposure to nocturnal light significantly increased plasma adrenalin levels. The effects of nocturnal light exposure on Pai-1 expression disappeared in adrenalectomized mice, although the changes in clock genes were still apparent. In conclusion, our results suggest that nocturnal light exposure, even for 1 h, alters hepatic Pai-1 gene expression by stimulating the adrenal pathway. Adrenalin secreted from the adrenal gland may be an important signaling mediator of the change in Pai-1 expression in response to nocturnal light exposure.
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Practical application of flavonoid-poor menu meals to the study of the bioavailability of bilberry anthocyanins in human subjects.
Biosci. Biotechnol. Biochem.
PUBLISHED: 07-07-2014
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Practical application of flavonoid-poor menus was evaluated on the bioavailability of anthocyanins as model flavonoids. Detectable amounts of flavonoids were not found in plasma and urine collected from 13 participants, who took the menus. After ingesting bilberry anthocyanins (919 ?mol), average plasma AUC0-6h, Cmax, Tmax values and urinary recovery were 386.0 nmol h/mL, 139.1 nM, 1.31 h and 0.21%, respectively.
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Quercetin-3-O-glucronide inhibits noradrenaline binding to ?2-adrenergic receptor, thus suppressing DNA damage induced by treatment with 4-hydroxyestradiol and noradrenaline in MCF-10A cells.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 02-20-2014
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Risk factors for breast cancer include estrogens such as 17?-estradiol (E2) and high stress levels. 4-Hydroxyestradiol (4-OHE2), a metabolite of E2 formed preferentially by cytochrome P450 1B1, is oxidized to E2-3,4-quinone, which reacts with DNA to form depurinating adducts that exert genotoxicity and carcinogenicity. Endogenous catecholamines such as adrenaline (A) and noradrenaline (NA) are released from the adrenal gland and sympathetic nervous system during exposure to stress. Here, we found that treatment with 4-OHE2 (3 ?M) and NA (3 nM) significantly induced the phosphorylation of histone H2AX (?-H2AX), one of the earliest indicators of DNA damage, and apurinic (AP) sites via the ?2-adrenergic receptor (?2-AR) in human mammary epithelial MCF-10A cells. As an inverse association between a higher intake of flavonoids and breast cancer risk has previously been suggested from epidemiological studies, we investigated the effects of quercetin-3-O-glucuronide (Q3G), a circulating metabolite of quercetin in the blood, on 4-OHE2- and NA-induced ?-H2AX and AP sites. Q3G (0.1 ?M) suppressed their induction and inhibited the binding of [(3)H]-NA to ?2-AR. These results suggest that Q3G acts as an ?2-AR antagonist and that it could be used as a chemopreventive agent for stress-promoted breast cancer.
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Depressive symptoms of female nursing staff working in stressful environments and their association with serum creatine kinase and lactate dehydrogenase - a preliminary study.
Biopsychosoc Med
PUBLISHED: 01-01-2014
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The activity of creatine kinase (CK) in serum has recently been reported to be potentially associated with several types of depression. The aim of this study is to evaluate whether serum enzymes, including CK, vary even in a healthy population with depressive symptoms caused by work-related stress. We gave questionnaires and blood examinations to 93 healthy female nursing home workers and did an enzyme-linked immunosorbent assay for the quantitative detection of CK isozyme muscle-type M chain (CK-MM) in serum.
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Potable water scarcity: options and issues in the coastal areas of Bangladesh.
J Water Health
PUBLISHED: 08-29-2013
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In the coastal areas of Bangladesh, scarcity of drinking water is acute as freshwater aquifers are not available at suitable depths and surface water is highly saline. Households are mainly dependent on rainwater harvesting, pond sand filters and pond water for drinking purposes. Thus, individuals in these areas often suffer from waterborne diseases. In this paper, water consumption behaviour in two southwestern coastal districts of Bangladesh has been investigated. The data for this study were collected through a survey conducted on 750 rural households in 39 villages of the study area. The sample was selected using a random sampling technique. Households choice of water source is complex and seasonally dependent. Water sourcing patterns, households preference of water sourcing options and economic feasibility of options suggest that a combination of household and community-based options could be suitable for year-round water supply. Distance and time required for water collection were found to be difficult for water collection from community-based options. Both household and community-based options need regular maintenance. In addition to installation of water supply facilities, it is necessary to make the residents aware of proper operation and maintenance of the facilities.
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Pu-erh tea suppresses diet-induced body fat accumulation in C57BL/6J mice by down-regulating SREBP-1c and related molecules.
Biosci. Biotechnol. Biochem.
PUBLISHED: 07-07-2013
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Although pu-erh tea has been shown to suppress hyperlipidemia, it is unclear how it modulates fatty acid synthase expression in mice fed on a high-fat diet. We investigated the effects of a pu-erh tea extract (PTE) on diet-induced body fat accumulation. C57BL/6J mice were fed a control diet, a high-fat diet (HFD), and HFD supplemented with 0.225% or 0.45% PTE for 70 d. Supplementation with PTE reduced the body weight gain, and the abdominal and liver fat accumulation. A significant difference in the triglyceride level were observed between the HFD control and HFD+0.45% PTE groups. A PTE intake tended to decrease sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) mRNA expression in the liver of the mice. These findings indicate that PTE reduced lipogenesis by down-regulating SREBP-1c and related molecules, leading to the suppression of body fat accumulation.
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Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans Cinnamon rat.
Clin Nutr
PUBLISHED: 04-13-2013
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BACKGROUND AND AIMS: Large-scale epidemiological studies have shown that drinking more than two cups of coffee per day reduces the risks of hepatitis and liver cancer. However, the heterogeneity of the human genome requires studies of experimental animal models with defined genetic backgrounds to evaluate the coffee effects on liver diseases. We evaluated the efficacy of coffee consumption with one of experimental animal models for human disease. METHOD: We used the Long Evans Cinnamon (LEC) rat, which onsets severe hepatitis and high incidence of liver cancer, due to the accumulation of copper and iron in livers caused by the genetic mutation in Atp7B gene, and leading to the continuous oxidative stress. We determined the expression of inflammation related genes, and amounts of copper and iron in livers, and incidence of the pre-neoplastic foci in the liver tissue of LEC rats. RESULTS: Coffee administration for 25 weeks delayed the occurrence of hepatitis by two weeks, significantly improved survival, reduced the expression of inflammatory cytokines, and reduced the incidence of small pre-neoplastic liver foci in LEC rats. There was no significant difference in the accumulation of copper and iron in livers, indicating that coffee administration does not affect to the metabolism of these metals. These findings indicate that drinking coffee potentially prevents hepatitis and liver carcinogenesis through its anti-inflammatory effects. CONCLUSION: This study showed the efficacy of coffee in the prevention of hepatitis and liver carcinogenesis in the LEC model.
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Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.
J Clin Biochem Nutr
PUBLISHED: 02-20-2013
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In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.
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Breast cancer and flavonoids - a role in prevention.
Curr. Pharm. Des.
PUBLISHED: 01-30-2013
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Endogenous estrogens, such as 17?-estradiol (E2), are implicated in the development of breast cancer. The putative mechanisms by which estrogens exert the carcinogenic effects have been recognized to involve the redox cycling of estrogen metabolites and subsequent estrogen-DNA adduct formation as well as the estrogen receptor-dependent pathway of estrogen-induced cell growth. The former pathway is regulated by phase I enzymes, mainly cytochrome P450 (CYP) 1A1, 1A2, and 1B1. Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2. Formed 4-OHE2 is further oxidized to semiquinones and quinones, which form DNA adducts, leading to mutagenic lesions. Consequently, CYP1B1 is highly expressed, and 4-OHE2 is predominantly detected in estrogen target neoplastic tissues. Moreover, invasion and metastasis are also involved in the development of breast cancer. Epidemiological studies suggest an inverse association between a higher intake of flavonoids and breast cancer risk. Flavonoids, which are widely distributed in the plant kingdom, have been recently reported as candidate compounds that can exert chemopreventive effects in estrogen-dependent or independent breast cancer. In this review, we provide a comprehensive overview of breast cancer and chemoprevention by flavonoids, mainly focusing on ER-mediated hormonal regulation, redox cycling of estrogen metabolites, and selective inhibition of CYP1B1.
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Organ-specific distribution of 7-chlorinated benz[a]anthracene and regulation of selected cytochrome P450 genes in rats.
J Toxicol Sci
PUBLISHED: 01-30-2013
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We previously reported that 14-day exposure to 7-chlorinated benz[a]anthracene (7-Cl-BaA), a new environmental pollutant, selectively induced hepatic cytochrome P450 (CYP)1A2 in rats, although treatment with its parent, benz[a]anthracene (BaA), induced CYP1A1, CYP1A2, and CYP1B1. In this study, to better understand the relative contribution of chlorination to the toxicity of polycyclic aromatic hydrocarbons (PAHs), we investigated the organ-specific distributions of 7-Cl-BaA and BaA in F334 rats. After 14 days of oral administration of 7-Cl-BaA or BaA at a concentration of 1 or 10 mg/kg body weight/day, both chemicals were detected in their plasma, which was collected 24 hr after the last administration, even at the lower dosage. Dose-dependent accumulation patterns were observed in the liver, muscle, kidney, spleen, heart, and lung. The 7-Cl-BaA concentrations in the organs were higher than those of the BaA. Furthermore, at the end of the exposure, 7-Cl-BaA specifically regulated several CYP genes in the heart more so than in other organs, although these inductions were not significant in the BaA treatment. 7-Cl-BaA might also stimulate the metabolic pathways of chemicals other than AhR-mediated metabolism, which is specific to normal PAHs, because of the alterations of CYP2J4, CYP4B1, and CYP17A1 expression in rats. In conclusion, our results imply that the chlorination of PAHs may change their organ-specific distribution and consequently alter their toxicological impacts compared to their parent PAHs.
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Bacteriological assessment of drinking water supply options in coastal areas of Bangladesh.
J Water Health
PUBLISHED: 09-28-2011
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This study was conducted to assess the bacteriological quality of alternative drinking water supply options in southwest coastal areas of Bangladesh. A total of 90 water samples were collected during both dry and wet seasons from household based rainwater harvesting systems (RWHSS), community based rain water harvesting systems (CRWHSs), pond-sand filters (PSFs) and ponds. The samples were evaluated for faecal coliform, Escherichia coli and Heterotrophic Plate Count, as well as Vibrio cholerae, Salmonella spp., Shigella spp. and Pseudomonas spp. Physico-chemical parameters (pH, electrical conductivity, and color) were also examined. In addition, sanitary inspections were conducted to identify faecal contamination sources. All options showed varying degrees of indicator bacterial contamination. The median E. coli concentrations measured for RWHSs, CRWHSS, PSFS, and ponds were 16, 7, 11, and 488 cfu/100 ml during the wet season, respectively. Vibrio cholerae 01/0139, Salmonella and Shigella spp. were not found in any samples. However, Vibrio cholerae Non-01/Non-0139 and Pseudomonas spp. were isolated from 74.4% and 91.1% of the water samples collected during the wet season. A maximum pH of 10.4 was found in CRWHSS. Estimation of the disease burden for all options in disability adjusted life years (DALYs) showed an increased disease burden during the wet season. According to sanitary inspections, poor maintenance and unprotected ponds were responsible for rainwater and PSF water contamination, respectively. The findings of the present study suggest that alternative drinking water supply options available in southwest coastal Bangladesh pose a substantial risk to public health.
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Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats.
Free Radic. Biol. Med.
PUBLISHED: 06-04-2011
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Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with ?-glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further identified using HPLC-tandem mass spectrometry. Oral administration of quercetin (50mg/kg body wt) attenuated the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming. The possible transport of quercetin derivatives into the brain tissue was reproduced in vitro by using a rat brain capillary endothelial cell line, a model of the blood-brain barrier. These results show that quercetin could be a potent nutrient that can access the brain and protect it from disorders associated with oxidative stress.
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Effects of spaced feeding on gene expression of hepatic transaminase and gluconeogenic enzymes in rats.
J Toxicol Sci
PUBLISHED: 06-02-2011
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Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities are widely used as sensitive markers of liver toxicity. However, these activities are also recognized to be altered by hormonal and nutritional modifications. We investigated the relationships between the activity and gene expression of the hepatic transaminases and the state of hepatic amino acid/glucose/fatty acid metabolism in the ad libitum fed (ALF) and spaced-fed (SF) rats. Acceleration of hepatic gluconeogenesis and fatty acid oxidation was noted in the SF rats. Expression of hepatic clock gene was also altered in the SF rats. Hepatic transaminase activities in the SF rats were higher than those in the ALF rats. These alterations were due to increases in the synthesis of hepatic ALT and AST proteins. In conclusion, the increased transaminase protein synthesis in the liver of the SF rats was considered to be related to the acceleration of hepatic gluconeogenesis under the conditions of spaced feeding.
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Val1483Ile polymorphism in the fatty acid synthase gene was associated with depressive symptoms under the influence of psychological stress.
J Affect Disord
PUBLISHED: 04-05-2011
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To study the association between lipid-metabolism and depressive symptoms, genetic polymorphisms in serotonin transporter linked promoter region (5-HTTLPR) and fatty acid synthase gene (FASN) were investigated.
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Effect of quercetin and glucuronide metabolites on the monoamine oxidase-A reaction in mouse brain mitochondria.
Nutrition
PUBLISHED: 03-03-2011
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Quercetin is a flavonoid found in plant foods and herbal medicines. It possesses antidepressant-like effects in forced swimming test-loaded rodents. We wanted to clarify the mechanism of action of dietary quercetin for exerting antidepressant-like effects. The effect of quercetin and its antioxidative metabolite quercetin 3-glucuronide (Q3GA) on the activity of mouse brain mitochondrial monoamine oxidase-A (MAO-A) was evaluated by measuring the deamination product of serotonin, 5-hydroxyindole acetaldehyde (5-HIAL).
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Feeble awake effects of plasminogen activator inhibitor type-1 in mice.
Behav. Brain Res.
PUBLISHED: 02-04-2011
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Plasminogen activator inhibitor-type 1 (PAI-1) is involved in the fibrinolytic system and shows its increased levels in diseases, e.g., obesity and sleep apnea syndrome. The aim of the study is to investigate whether PAI-1 affects sleep-wake patterns in mice. When recombinant mouse PAI-1 was administered intraperitoneally, only rapid but short increases in time spent awake were observed after 20 or 100 ?g/kg, although its plasma concentration was kept high for an hour. The results suggest that PAI-1 may serve its role rather as a marker than an initiator of disturbed sleep.
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Effects of animal care procedures on plasma corticosterone levels in group-housed mice during the nocturnal active phase.
Exp. Anim.
PUBLISHED: 10-30-2010
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C57BL/6 mice were housed five per cage on a 12:12 h light/dark cycle. All animal care, including bed cleaning, was carried out during the nonactive phase. After 2 weeks, mean plasma corticosterone levels, collected during the nonactive (ZT6) and active (ZT18) phases, were 66.0 and 270.9 ng/ml, respectively. The values at ZT18 gradually increased in the order of the mice used for blood collection, but not at ZT6. When animal care was carried out at ZT18, the increasing pattern of plasma corticosterone levels previously observed at ZT18 was less pronounced after 2 weeks of acclimatization, and was not observed after 4 weeks. Therefore, animal care should be carried out in the active phase for at least 4 weeks before experiments involving stress responses in the active phase.
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Relationships between plasma and tissue transaminase activities in rats maintained under different feeding conditions.
J Toxicol Sci
PUBLISHED: 10-09-2010
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In order to verify the nutritional aspect of alterations of the plasma and tissue transaminase activities, rats were fed 4 hr per day for 35 days (the spaced-fed (SF) rats) and the time course of the alterations in plasma and tissue transaminase activity was compared with those in the ad libitum fed (ALF) rats. Plasma transaminase activities were stable throughout the experiment period in the ALF rats. In the SF rats there were alterations in the plasma alanine aminotransferase (ALT) activities, the direction of which was different between the early phase and late phase of the experiment period; plasma ALT activities decreased in the early phase and gradually increased in the late phase. Plasma aspartate aminotransferase (AST) activities were stable in the SF rats throughout the experiment period as well as the ALF rats. The decreases in plasma ALT activities in the early phase were considered to be related to decreases in ALT activities in the small intestinal mucosa (SI mucosa). On the other hand, the increases in plasma ALT activities in the late phase were considered to be related to increases in ALT activities in the liver. Multiple regression analyses (MRAs) revealed that plasma ALT activities in the SF rats could be estimated by the ALT activities in the SI mucosa and liver. From these results, the alterations of the plasma ALT activities in the SF rats could be explained by those in the SI mucosa and liver under the conditions in our study.
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Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress.
Biosci. Biotechnol. Biochem.
PUBLISHED: 10-07-2010
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The mortality of individuals suffering from depression has been increasing, especially post-menopausal women; therefore, their care and treatment are important to maintain a high quality of life. In the present study, we evaluated the antidepressant-like effects of a major isoflavonoid, genistein (4,5,7-trihydroxyisoflavone), using a behavioral model of depression, the forced swimming test (FST), in ovariectomized rats. Daily administration of genistein to ovariectomized rats at a dosage of 10 mg/kg of body weight/d for 14 d significantly reduced the immobility time during the FST without changing motor dysfunction. On the other hand, a higher dosage, 100 mg/kg/d, did not have any effects on the immobility time compared with the vehicle control. Repeated administration of genistein at 10 mg/kg of body weight did not affect serotonergic activities in the hippocampus compared to the vehicle control in ovariectomized rats. A 5-min FST trial stimulated these activities. On the other hand, repeated pretreatment with genistein protected against changes in activity during the FST trial. These results suggest that daily consumption of genistein 10 mg/kg/d might have antidepressant-like effect on ovariectomized rats by regulating changes in serotonergic metabolism in the hippocampus under stressful conditions.
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Selective inhibition of methoxyflavonoids on human CYP1B1 activity.
Bioorg. Med. Chem.
PUBLISHED: 05-26-2010
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Cytochrome P450 (CYP) 1B1 catalyzes 17beta-estradiol (E(2)) to predominantly carcinogenic 4-hydroxy-E(2), whereas CYP1A1 and 1A2 convert E(2) to non-carcinogenic 2-hydroxy-E(2). Hence, selective inhibition of CYP1B1 is recognized to be beneficial for the prevention of E(2) related breast cancer. In this study, we first evaluated the structure-property relationship of 18 major flavonoids on inhibiting enzymatic activity of CYP1A1, 1A2 and 1B1 by using an ethoxyresorufin O-deethylation assay. Flavones and flavonols indicated relatively strong inhibitory effects on CYP1s compared with flavanone that does not have the double bond between C-positions 2 and 3 on the C-ring. Flavonoids used in this study selectively inhibited CYP1B1 activity. In particular, methoxy types of flavones and flavonols such as chrysoeriol and isorhamnetin showed strong and selective inhibition against CYP1B1. To understand why selective inhibition was observed, we carried out a molecular docking analysis of these methoxyflavonoids with the 2-3 double bond and CYP1s. The results suggested that chrysoeriol and isorhamnetin fit well into the active site of CYP1B1, but do not fit into the active site of CYP1A2 and 1A1 because of steric collisions between the methoxy substituent of these methoxyflavonoids and Ser-122 in CYP1A1 and Thr-124 in CYP1A2. In conclusion, our results demonstrate: (1) strong inhibitory effects of flavonoids on CYP1 activities require the 2-3 double bond on the C-ring; (2) methoxyflavonoids with the 2-3 double bond had strong and selective inhibition against CYP1B1, suggesting chemopreventive flavonoids for E(2) related breast cancer; and (3) binding specificity of these methoxyflavonoids is based on the interactions between the methoxy groups and specific CYP1s residues.
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Inhibitory effects of chrysoeriol on DNA adduct formation with benzo[a]pyrene in MCF-7 breast cancer cells.
Toxicology
PUBLISHED: 04-21-2010
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Cytochrome P450 (CYP) 1 families including CYP1A1, 1A2 and 1B1 are well known to be deeply involved in the initiation of several cancers, due to the fact that they activate environmental pro-carcinogens to form ultimate carcinogens. Benzo[a]pyrene (BaP) is one of the major classes of prototypical pro-carcinogen. It is activated by the CYP1 family to its ultimate carcinogenic forms, mainly BaP-7,8-diol-9,10-epoxide (BPDE), and it forms adducts with DNA. This has been recognized to be a major initiation pathway for cancer. Our previous study demonstrated that chrysoeriol, which is a dietary methoxyflavonoid, selectively inhibited CYP1B1 enzymatic activity and might protect the CYP1B1 related-diseases such as breast cancer. In the present study, we further examined the effects of chrysoeriol on the other initiation pathway of cancer relating to the CYP1 family with BaP in human breast cancer MCF-7 cells. The effects of chrysoeriol on the formation of BPDE-DNA adducts were analyzed specifically using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. When MCF-7 cells were incubated with 2 microM BaP for 24h, three types of BPDE-dG adducts, especially (+)-trans-BPDE-dG as the dominant adduct, were detected. Co-treatment of MCF-7 cells with 10 microM chrysoeriol and BaP remarkably reduced (+)-trans-BPDE-dG formation. Chrysoeriol (1-10 microM) dose-dependently inhibited both EROD activity and the gene expressions of CYP1A1, 1B1 and 1A2 stimulated by treatment with BaP. In addition, the same amounts of chrysoeriol significantly inhibited the binding of BaP to the aryl hydrocarbon receptor (AhR), which is the key factor concerning the induction of the CYP1 families. In conclusion, our results clearly indicate that chrysoeriol inhibited the formation of BPDE-DNA adducts via regulation of the AhR pathway stimulated by BaP. As a consequence chrysoeriol may be involved in the chemoprevention of environmental pro-carcinogens such as BaP.
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Proteomic identification of serum proteins associated with stress-induced gastric ulcers in fasted rats.
Biosci. Biotechnol. Biochem.
PUBLISHED: 04-07-2010
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Several physical and psychological stresses frequently become triggers for gastrointestinal disorders such as ulcer. In this study, we tried to identify serum proteins as potential biomarkers for the evaluation of stress-induced gastric ulcer. By proteomic analysis using rats with gastric ulcer induced by water immersion and restraint (WIR) stress as an animal model, we found quantitative changes in several serum proteins, including creatine kinase muscle M chain (CK-M) and apolipoprotein A-IV (ApoA4) in the stressed rats. On western blotting and enzyme-linked immunosorbent assay (ELISA), we confirmed that serum CK-M was remarkably increased by WIR stress. However, ApoA4 appeared to be decreased by fasting, but not WIR stress, which is usually applied prior to WIR stress. The findings suggest that these two serum proteins might be useful as biomarkers, CK-M for stress-induced gastric ulcer and ApoA4 for starvation.
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Distribution and excretion of bilberry anthocyanins [corrected] in mice.
J. Agric. Food Chem.
PUBLISHED: 08-12-2009
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The physiology and tissue distribution of bilberry anthocyanins were studied in mice. After oral administration of bilberry extract (100 mg/kg body weight), both unmodified and methylated anthocyanins appeared in the plasma. The plasma concentration of total anthocyanins reached a maximum of 1.18 +/- 0.3 microM after 15 min and then sharply decreased. Their urinary excretion was highest between 0 and 6 h after administration and had ceased by 24 h. The total quantities of bilberry anthocyanins excreted into urine represented 1.88% (range, 0.62% to 2.45%) of consumed anthocyanins. Thirteen anthocyanins were identified in bilberry extracts. Of these, malvidin-3-glucoside and -3-galactoside were the principal anthocyanins in the plasma 60 min after administration. When mice were maintained for 2 weeks on a diet containing 0.5% of bilberry extracts, the plasma concentration of anthocyanins reached a maximum of 0.26 muM. Anthocyanins were detected only in the liver, kidney, testes, and lung, with maximum tissue concentrations of 605, 207, 149, and 116 pmol/g, respectively. In these organs, malvidin-3-glucoside and -3-galactoside were the predominant anthocyanins. Anthocyanins were not detectable in the spleen, thymus, heart, muscle, brain, white fat, or eyes. We conclude that bilberry anthocyanins were absorbed into the body and distributed in specific organs, particularly the liver, kidney, and testis. The most common anthocyanins in tissues were malvidin glycosides.
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Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats.
Free Radic. Res.
PUBLISHED: 08-06-2009
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Quercetin has strong antioxidant potency. Quercetin-3-O-sulphate (Q3S) and quercetin-3-O-glucuronide (Q3GA) are the main circulating metabolites after consumption of quercetin-O-glucoside-rich diets by humans. However, information about how these quercetin metabolites function in vivo is limited. Hence, this study evaluated the efficacy of Q3S and Q3GA for the protection of oxidative injury using in vitro and in vivo experiments. Peroxynitrite-mediated hepatic injury in rats was induced by administration of galactosamine/lipopolysaccharide (GalN/LPS). Twenty-four hours after GalN/LPS treatment, plasma ALT and AST levels delta increased significantly. However, pretreatment with 4(G)-alpha-D-glucopyranosyl rutin, a quercetin glycoside (30 mg/kg body weight), prevented these increases and reduced nitrotyrosine formation, indicating that consumption of quercetin glycosides prevent oxidative hepatotoxicity. Moreover, physiological levels of Q3S and Q3GA (1 microM) effectively prevented peroxynitrite-induced nitrotyrosine formation in human serum albumin in in vitro experiments. These findings indicate peroxynitrite-induced oxidative hepatotoxicity is protected by the in vivo metabolites of quercetin, Q3S and Q3GA.
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Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats.
J Toxicol Sci
PUBLISHED: 08-05-2009
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Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are widely used as sensitive markers of possible tissue damage, particularly liver toxicity. Lipid-lowering drugs, such as fibrates, slightly increase serum transaminase levels in humans, but there is little evidence that the phenomenon is related to drug-induced liver injury (DILI). Some in vitro studies have indicated that the elevations of serum transaminase activities after treatment of humans with fenofibrate, one of the fibrates, are related to increased transaminase synthesis in the hepatocytes rather than to transaminase leakage from the hepatocytes associated with cell lysis. In this study, male F344/DuCrlCrlj (Fischer) rats were treated once with fenofibrate at a dose level of 400 mg/kg and the relationships between the pharmacological effects, blood and hepatic transaminase activities and the gene expression of the transaminases in the liver were investigated. Fenofibrate treatment slightly increased plasma transaminase activities in rats with the findings directly related to the pharmacological action of the drug. The increases were in parallel with increases in hepatic transaminase activities associated with increases in the transaminase genes in the liver and were not considered to be a consequence of hepatotoxicity from the drug. The modification in transaminase gene expression is likely to be secondary to the pharmacological action of fenofibrate. The evidence obtained in our study underlines the importance of gene regulation as a possible alternative mechanism for increased blood transaminase activities.
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A methoxyflavonoid, chrysoeriol, selectively inhibits the formation of a carcinogenic estrogen metabolite in MCF-7 breast cancer cells.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 07-05-2009
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A 17beta-estradiol (E(2)) is hydrolyzed to 2-hydroxy-E(2) (2-OHE(2)) and 4-hydroxy-E(2) (4-OHE(2)) via cytochrome P450 (CYP) 1A1 and 1B1, respectively. In estrogen target tissues including the mammary gland, ovaries, and uterus, CYP1B1 is highly expressed, and 4-OHE(2) is predominantly formed in cancerous tissues. In this study, we investigated the inhibitory effects of chrysoeriol (luteorin-3-methoxy ether), which is a natural methoxyflavonoid, against activity of CYP1A1 and 1B1 using in vitro and cultured cell techniques. Chrysoeriol selectively inhibited human recombinant CYP1B1-mediated 7-ethoxyresorufin-O-deethylation (EROD) activity 5-fold more than that of CYP1A1-mediated activity in a competitive manner. Additionally, chrysoeriol inhibited E(2) hydroxylation was catalyzed by CYP1B1, but not by CYP1A1. Methylation of 4-OHE(2), which is thought to be a detoxification process, was not affected by the presence of chrysoeriol. In human breast cancer MCF-7 cells, chrysoeriol did not affect the gene expression of CYP1A1 and 1B1, but significantly inhibited the formation of 4-methoxy E(2) without any effects on the formation of 2-methoxy E(2). In conclusion, we present the first report to show that chrysoeriol is a chemopreventive natural ingredient that can selectively inhibit CYP1B1 activity and prevent the formation of carcinogenic 4-OHE(2) from E(2.).
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Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice.
Physiol. Genomics
PUBLISHED: 05-29-2009
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To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate). Gene Ontology analysis of these differentially expressed genes indicated that the stress remarkably downregulated the lipid metabolism-related pathway through peroxisome proliferator-activated receptor-alpha, while the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1, Golgi vesicle transport, and secretory pathway-related genes were significantly upregulated. These results suggest that isolation for 30 days with a mild and consecutive social stress regulates the systems for lipid metabolism and also causes endoplasmic reticulum stress in mouse liver.
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Social isolation stress induces hepatic hypertrophy in C57BL/6J mice.
J Toxicol Sci
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We previously reported that social isolation stimulated a stress response leading to increasing plasma corticosterone level and disruption of the hepatic lipid metabolism-related pathway, without changing body and organ weights, in mice after 4 weeks of social isolation stress, compared with the grouped-housing control (5 mice/cage). In this study, we evaluated the effects of social isolation stress for an extended period on physiologic changes in male C57BL/6J mice. Plasma corticosterone was reduced after 13 weeks, indicating mice might adapt to social isolation stress. However, body and visceral fat weights were significantly increased in combination with hepatic hypertrophy, and significant decreases in levels of triglyceride and adiponectin in plasma were observed. In conclusion, it is tempting to speculate that mice exposed to social isolation stress for 13 continuous weeks could be at an increased risk of overweight with hepatic hypertrophy. Our results also imply that physiological changes, at least fatty acid metabolism, under stress exposure might be an important factor when evaluating the chronic effects of environmental chemicals.
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Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.
J Toxicol Sci
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Mammals, including human beings, have a circadian clock system to regulate behavioral and physiological processes. In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents). Male C3H/He mice were treated intraperitoneally with ENU (12.5 or 25 mg/kg body weight) at zeitgeber time (ZT) 3 in the light period or ZT15 in the dark period, and then the time courses of the frequencies of the MNRETs were determined. The frequencies of the MNRETs induced by ENU increased time-dependently and peaked at 48 hr after treatment for ZT3 and ZT15, and were obviously higher in the ZT15 treatment group than the ZT3 treatment group. The MNRETs were measured at 48 hr after treatment with ENU (25 mg/kg body weight) at various dosing times (ZT0, 3, 6, 12, 15 and 18). The frequencies of the MNRETs in mice treated at ZT0, 15 and 18 were significantly higher than those in mice treated at ZT3, 6 and 12. These results suggest that genotoxic sensitivity to chemicals in mouse bone marrow is different between light and dark periods maybe due to different biological responses (detoxification, cell cycle, DNA repair, etc.) related to circadian rhythms.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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