keyword
MENU ▼
Read by QxMD icon Read
search

PXR

keyword
https://www.readbyqxmd.com/read/28199000/overexpression-of-pregnane-x-and-glucocorticoid-receptors-and-the-regulation-of-cytochrome-p450-in-human-epileptic-brain-endothelial-cells
#1
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Imad M Najm, Nicola Marchi, Damir Janigro
OBJECTIVE: Recent evidence suggests a metabolic contribution of cytochrome P450 enzymes (CYPs) to the drug-resistant phenotype in human epilepsy. However, the upstream molecular regulators of CYP in the epileptic brain remain understudied. We therefore investigated the expression and function of pregnane xenobiotic (PXR) and glucocorticoid (GR) nuclear receptors in endothelial cells established from post-epilepsy surgery brain samples. METHODS: PXR/GR localization was evaluated by immunohistochemistry in specimens from subjects who underwent temporal lobe resections to relieve drug-resistant seizures...
February 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28198586/influence-of-a-critical-single-nucleotide-polymorphism-on-nuclear-receptor-pxr-promoter-function
#2
Manjul Rana, Poonam Coshic, Ravinder Goswami, Rakesh K Tyagi
The Pregnane and Xenobiotic Receptor (PXR; NR1I2), is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. It is expressed at higher levels primarily in liver and intestine as compared to the levels in several other organs. It is activated by a broad spectrum of xenobiotics and endobiotics. The primary function of PXR is to regulate the expression of drug metabolizing enzymes and transporters and prevent the accumulation of toxic chemicals in the body, thereby maintaining body's homeostasis...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28192885/polyphenols-rich-passiflora-leschenaultii-leaves-modulating-farnesoid-x-receptor-and-pregnane-x-receptor-against-paracetamol-induced-hepatotoxicity-in-rats
#3
Saravanan Shanmugam, Dhivya Sivaraj, Bruno Dos Santos Lima, Paula Dos Passos Menezes, Yasmim Maria Barbosa Gomes de Carvalho, Adriano Antunes de Souza Araújo, Narendra Narain, Mairim Russo Serafini, Lucindo José Quintans Júnior, Luciana Scotti, Marcus Tulius Scotti, Thangaraj Parimelazhagan
The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed...
February 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#4
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28186385/activating-nuclear-xenobiotic-receptors-and-triggering-er-stress-and-hepatic-cytochromes-p450-systems-in-quails-coturnix-c-coturnix-during-atrazine-exposure
#5
Zheng-Hai Du, Lei Qin, Jia Lin, Yan-Chun Sun, Jun Xia, Cong Zhang, Xue-Nan Li, Jin-Long Li
Atrazine (ATR) is one of the most widely detected contaminant in the ecosystem. Nuclear xenobiotic receptors are activated by herbicides and induce the transcription of CYP450 isoforms involved in xenobiotic metabolism and transport. However, little is known about hepatic nuclear xenobiotic receptors in birds are responsible for ATR-induced hepatotoxicity via regulating the cytochrome P450 enzyme systems (CYP450s). The objective of this study was to investigate the mechanism of ATR hepatotoxicity in quails...
February 10, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28173640/tanshinone-iia-protects-endothelial-cells-from-h2o2-induced-injuries-via-pxr-activation
#6
Haiyan Zhu, Zhiwu Chen, Zengchun Ma, Hongling Tan, Chengrong Xiao, Xianglin Tang, Boli Zhang, Yuguang Wang, Yue Gao
Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established...
February 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28153492/sex-and-age-dependent-gene-expression-in-human-liver-an-implication-for-drug-metabolizing-enzymes
#7
Yasuhiro Uno, Ryo Takata, Go Kito, Hiroshi Yamazaki, Kazuko Nakagawa, Yusuke Nakamura, Tetsuya Kamataki, Toyomasa Katagiri
Sex and age differences in hepatic expression of drug-metabolizing enzyme genes could cause variations in drug metabolism, but has not been fully elucidated, especially in Asian population. In this study, the global expression of human hepatic genes was analyzed by microarrays in 40 Japanese subjects (27 males and 13 females). Thirty-five sex-biased genes were identified (P < 0.005). Whereas, 60 age-biased genes in two age groups, <60 years and ≥70 years (P < 0.001), were identified in males...
February 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28128444/suppression-of-carboxylesterases-by-imatinib-mediated-by-the-downregulation-of-pregnane-x-receptor
#8
Wenjing Luo, Yu Xin, Xia Zhao, Feng Zhang, Changqing Liu, Hongwei Fan, Tao Xi, Jing Xiong
BACKGROUND AND PURPOSE: Imatinib mesylate (IM) is first-line anti-chronic myeloid leukemia (CML) therapy as a specific inhibitor of BCR-ABL tyrosine kinase. IM in combination with other drugs has been widely applied in CML treatment, thus the influence of IM on drug metabolism enzymes (DMEs) is crucial to be understood in suggesting rational drug administration. Carboxylesterases (CESs) are important enzymes catalyzing hydrolytic biotransformation and play vital roles in the metabolism of numerous clinical drugs...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28128437/schisandrol-b-protects-against-cholestatic-liver-injury-through-pregnane-x-receptor
#9
Hang Zeng, Yiming Jiang, Pan Chen, Xiaomei Fan, Dongshun Li, Aiming Liu, Xiaochao Ma, Wen Xie, Peiqing Liu, Frank J Gonzalez, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid is the only FDA-approved drug for limited cholestatic liver diseases, and thus the development of new therapeutic approaches is of great importance. This study aimed to evaluate the anti-cholestasis effect of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera. EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against lithocholic acid (LCA)-induced intrahepatic extrahepatic cholestasis was evaluated in mice...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28118809/involvement-of-protoporphyrin-ix-accumulation-in-the-pathogenesis-of-isoniazid-rifampicin-induced-liver-injury-the-prevention-of-curcumin
#10
Leiyan He, Yaoxue Guo, Ye Deng, Chun Li, Chengzi Zuo, Wenxing Peng
Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively...
February 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28115221/epigallocatechin-gallate-induces-a-hepatospecific-decrease-in-the-cyp3a-expression-level-by-altering-intestinal-flora
#11
Nobutomo Ikarashi, Sosuke Ogawa, Ryuta Hirobe, Risako Kon, Yoshiki Kusunoki, Marin Yamashita, Nanaho Mizukami, Miho Kaneko, Nobuyuki Wakui, Yoshiaki Machida, Kiyoshi Sugiyama
In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined...
January 21, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#12
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28077325/role-of-14-3-3-sigma-in-over-expression-of-p-gp-by-rifampin-and-paclitaxel-stimulation-through-interaction-with-pxr
#13
So Won Kim, Md Hasanuzzaman, Munju Cho, Nam Hyun Kim, Hye-Young Choi, Jung Woo Han, Hyun June Park, Ji Won Oh, Jae-Gook Shin
In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90β-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90β-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28064419/pharmacokinetics-and-pharmacogenetics-of-carbamazepine-in-children
#14
Natasa Djordjevic, Slobodan M Jankovic, Jasmina R Milovanovic
Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1...
January 7, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28058446/hepatotoxic-effects-of-cyproconazole-and-prochloraz-in-wild-type-and-hcar-hpxr-mice
#15
Philip Marx-Stoelting, Katrin Ganzenberg, Constanze Knebel, Flavia Schmidt, Svenja Rieke, Helen Hammer, Felix Schmidt, Oliver Pötz, Michael Schwarz, Albert Braeuning
The agricultural fungicides cyproconazole and prochloraz exhibit hepatotoxicity in rodent studies and are tumorigenic following chronic exposure. Both substances are suspected to act via a CAR (constitutive androstane receptor)/PXR (pregnane-X-receptor)-dependent mechanism. Human relevance of these findings is under debate. A 28-day toxicity study was conducted in mice with humanized CAR and PXR (hCAR/hPXR) with two dose levels (50 or 500 ppm) of both substances, using the model CAR activator phenobarbital as a reference...
January 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28043194/differential-regulation-of-intestinal-efflux-transporters-by-pregnancy-in-mice
#16
Jamie E Moscovitz, Gabriel Yarmush, Guadalupe Herrera-Garcia, Grace L Guo, Lauren M Aleksunes
1. In the intestines, the nuclear receptors farnesoid X receptor (Fxr) and pregnane X receptor (Pxr) regulate the transcription of metabolizing enzymes and transporters that dictate the absorption of nutrients and xenobiotics. 2. Here, we sought to determine whether Fxr and Pxr signaling pathways are disrupted in response to high-circulating concentrations of steroid hormones late in pregnancy leading to altered transporter expression. To test this, ileum were collected from virgin and pregnant C57BL/6 mice on gestation days 14, 17 and 19...
January 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28027470/performance-of-a-novel-atrazine-induced-cerebellar-toxicity-in-quail-coturnix-c-coturnix-activating-pxr-car-pathway-responses-and-disrupting-cytochrome-p450-homeostasis
#17
Jun Xia, Lei Qin, Zheng-Hai Du, Jia Lin, Xue-Nan Li, Jin-Long Li
Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum...
December 18, 2016: Chemosphere
https://www.readbyqxmd.com/read/28025333/modulation-of-bilirubin-neurotoxicity-by-the-abcb1-transporter-in-the-ugt1-lethal-mouse-model-of-neonatal-hyperbilirubinemia
#18
Luka Bočkor, Giulia Bortolussi, Simone Vodret, Alessandra Iaconcig, Jana Jašprová, Jaroslav Zelenka, Libor Vitek, Claudio Tiribelli, Andrés F Muro
Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma...
December 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28006928/sufentanil-and-midazolam-dosing-and-pharmacogenetic-factors-in-pediatric-analgosedation-and-withdrawal-syndrome
#19
K Hronová, P Pokorná, L Posch, O Slanař
Our aim was to describe the effect of dosing and genetic factors on sufentanil- and midazolam-induced analgosedation and withdrawal syndrome (WS) in pediatric population. Analgosedation and withdrawal syndrome development were monitored using COMFORT-neo/-B scores and SOS score. Length of therapy, dosing of sufentanil and midazolam were recorded. Genotypes of selected candidate polymorphisms in CYP3A5, COMT, ABCB1, OPRM1 and PXR were analysed. In the group of 30 neonates and 18 children, longer treatment duration with midazolam of 141 h (2 - 625) vs...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/28006925/bile-acids-nuclear-receptors-and-cytochrome-p450
#20
J Juřica, G Dovrtělová, K Nosková, O Zendulka
This review summarizes the importance of bile acids (BA) as important regulators of various homeostatic mechanisms with detailed focus on cytochrome P450 (CYP) enzymes. In the first part, synthesis, metabolism and circulation of BA is summarized and BA are reviewed as physiological ligands of nuclear receptors which regulate transcription of genes involved in their metabolism, transport and excretion. Notably, PXR, FXR and VDR are the most important nuclear receptors through which BA regulate transcription of CYP genes involved in the metabolism of both BA and xenobiotics...
December 21, 2016: Physiological Research
keyword
keyword
107627
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"