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https://www.readbyqxmd.com/read/28944315/is-chronic-ahr-activation-by-rapidly-metabolized-ligands-safe-for-the-treatment-of-immune-mediated-diseases
#1
Allison K Ehrlich, Nancy I Kerkvliet
There is a long standing perception that AhR ligands are automatically disqualified from pharmaceutical development due to their induction of Cyp1a1 as well as their potential for causing "dioxin-like" toxicities. However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy. One area of exploration is focused on the activation of AhR to promote the generation of regulatory T cells, which control the intensity and duration of immune responses...
February 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/28923436/changes-in-hepatic-gene-expression-and-serum-metabolites-after-oral-administration-of-overdosed-vitamin-e-loaded-nanoemulsion-in-rats
#2
Chae Young Park, Chul Ho Jang, Do Yup Lee, Hyung Taek Cho, Young Jun Kim, Yoo Heon Park, Jee-Young Imm
Vitamin-E-loaded nanoemulsion (Vit E-NE) was produced, and the effects of repeated oral administration of Vit E-NE (2 g/kg/day) for five days on hepatic gene expression and serum metabolites were investigated in rats. The mean particle diameter and zeta potential of Vit E-NE was 112 nm and 56 mV, respectively. Vit E-NE administered rats showed significantly higher triglyceride content than of standard diet (control) or Vit E control emulsion (Vit E-CE) group but no toxicity symptoms were found in blood biochemical analysis...
September 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28920616/vitamin-c-protects-piglet-liver-against-zearalenone-induced-oxidative-stress-by-modulating-expression-of-nuclear-receptors-pxr-and-car-and-their-target-genes
#3
Baoming Shi, Yang Su, Siying Chang, Yuchen Sun, Xiangyu Meng, Anshan Shan
Zearalenone (ZEN), one of the most common mycotoxins found in human food and animal feed, has been shown to be effectively detoxified by vitamin C (Vc). The aim of this study was to investigate how vitamin C protects the piglet liver against oxidative stress induced by ZEN. A total of thirty-two healthy female crossbred weaning piglets (Duroc × Landrace × Large white) with an initial weight of 12.27 ± 0.30 kg were randomly divided into four treatment groups of eight piglets per group. The dietary treatments included two zearalenone levels (0 mg kg(-1) and 1...
September 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28920417/effects-of-deoxynivalenol-and-zearalenone-contaminated-feed-on-the-gene-expression-profiles-in-the-kidneys-of-piglets
#4
Kondreddy Eswar Reddy, Woong Lee, Jin Young Jeong, Yookyung Lee, Hyun-Jeong Lee, Min Seok Kim, Dong-Woon Kim, Dongjo Yu, Ara Cho, Young Kyoon Oh, Sung Dae Lee
Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0...
September 18, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28916285/profiling-of-bisphenol-s-towards-nuclear-receptors-activities-in-human-reporter-cell-lines
#5
Ondrej Zenata, Zdenek Dvorak, Radim Vrzal
Bisphenol S (BPS) is heat-stable structural analog of bisphenol A (BPA), a known endocrine disruptor. Due to the effort to replace BPA with BPS, it is essential to know if BPS is suitable non-toxic replacement without reported deleterious effects of BPA. Since most of the BPA effects are ascribed to its ability to activate nuclear receptors, we screened some prominent members of this family in order to confirm or refute some recent findings. We found that BPS insignificantly activated aryl hydrocarbon receptor (AhR) in reporter gene assay and no induction of AhR target gene CYP1A1 was observed in human hepatocytes (HH)...
September 12, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28892018/antioxidant-artemisia-princeps-extract-enhances-the-expression-of-filaggrin-and-loricrin-via-the-ahr-ovol1-pathway
#6
Akiko Hirano, Masashi Goto, Tsukasa Mitsui, Akiko Hashimoto-Hachiya, Gaku Tsuji, Masutaka Furue
The Japanese mugwort, Artemisia princeps (yomogi in Japanese), has anti-inflammatory and antioxidant effects. Skin care products containing Artemisia princeps extract (APE) are known to improve dry skin symptoms in atopic dermatitis. Atopic dry skin is associated with a marked reduction of skin barrier proteins, such as filaggrin (FLG) and loricrin (LOR). Recently, aryl hydrocarbon receptor (AHR), and its downstream transcription factor OVO-like 1 (OVOL1), have been shown to regulate the gene expression of FLG and LOR...
September 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28887105/the-significance-of-polymorphism-and-expression-of-oestrogen-metabolism-related-genes-in-chinese-women-with-premature-ovarian-insufficiency
#7
Chunrong Qin, Yong Chen, Qing Lin, Jilong Yao, Weiqing Wu, Jiansheng Xie
The aim of this study was to investigate whether polymorphism and expression of CYP17, CYP1A1, COMT and SULT1A1 affected the risk of idiopathic primary ovarian insufficiency (POI) in Chinese women. DNA sequencing and real-time PCR were used to detect these genes in 132 cases of idiopathic POI and 132 normal women. A significant increase in the C allele of CYP17 (rs743572) polymorphism was observed in women with POI compared with controls (PFDR = 0.046). A significant decrease was observed in the C allele of CYP1A1 (rs4646903) in women with POI compared with controls (PFDR = 0...
July 18, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28882992/novel-pathways-of-ponatinib-disposition-catalyzed-by-cyp1a1-involving-generation-of-potentially-toxic-metabolites
#8
De Lin, Rumen Kostov, Jeffrey T-J Huang, Colin J Henderson, C Roland Wolf
Ponatinib, a pan-BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML), causes severe side effects including vascular occlusions, pancreatitis, and liver toxicity, although the underlying mechanisms remain unclear. Modifications of critical proteins through reactive metabolites are thought to be responsible for a number of adverse drug reactions. In vitro metabolite screening of ponatinib with human liver microsomes and glutathione revealed unambiguous signals of ponatinib-glutathione (P-GSH) adducts...
October 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28882640/toxicity-of-the-main-electronic-cigarette-components-propylene-glycol-glycerin-and-nicotine-in-sprague-dawley-rats-in-a-90-day-oecd-inhalation-study-complemented-by-molecular-endpoints
#9
Blaine Phillips, Bjoern Titz, Ulrike Kogel, Danilal Sharma, Patrice Leroy, Yang Xiang, Grégory Vuillaume, Stefan Lebrun, Davide Sciuscio, Jenny Ho, Catherine Nury, Emmanuel Guedj, Ashraf Elamin, Marco Esposito, Subash Krishnan, Walter K Schlage, Emilija Veljkovic, Nikolai V Ivanov, Florian Martin, Manuel C Peitsch, Julia Hoeng, Patrick Vanscheeuwijck
While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics...
September 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28882572/identification-of-essential-transcription-factors-for-adequate-dna-damage-response-after-benzo-a-pyrene-and-aflatoxin-b1-exposure-by-combining-transcriptomics-with-functional-genomics
#10
Evelyn Smit, Terezinha Souza, Danyel G J Jennen, Jos C S Kleinjans, Twan van den Beucken
DNA damage mediates widespread changes in transcription through activation or repression of transcription factors (TFs). However, the consequences of regulating specific TFs for the outcome of the DNA repair process remain incompletely understood. Here, we combined transcriptomics and TF binding prediction with functional genomics to identify TFs essential for adequate DNA repair in HepG2 liver cells after a non-cytotoxic dose of carcinogens benzo(a)pyrene (BaP) (2μM) and aflatoxin B1 (AFB1) (5μM). BaP and AFB1 induced a largely common transcriptional response, mediated by similar TFs...
September 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28882023/apex1-polymorphism-and-mercaptopurine-related-early-onset-neutropenia-in-pediatric-acute-lymphoblastic-leukemia
#11
Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang
Purpose: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. Materials and Methods: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients...
September 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28879796/assessment-of-the-pulmonary-cyp1a1-metabolism-of-mavoglurant-afq056-in-rat
#12
Yildiz Yilmaz, Kenichi Umehara, Gareth Williams, Thomas Faller, Hilmar Schiller, Markus Walles, Stephan Kraehenbuehl, Gian Camenisch, Nenad Manevski
1. AFQ056 phenotyping results indicate that CYP1A1 is responsible for the formation of the oxidative metabolite, M3. In line with the predominant assumption that CYP1A1 is mainly expressed in extrahepatic tissues, only traces of M3 were detected in hepatic systems. The aim of this study was to investigate the pulmonary CYP1A1 mediated metabolism of AFQ056 in rat. 2. Western blot analysis confirmed that CYP1A1 is expressed in rat lung albeit at low levels. M3 formation was clearly observed in recombinant rat CYP1A1, lung microsomes and lung tissue slices and was strongly inhibited by ketoconazole in the incubations...
September 7, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28868835/association-of-cyp1a1-2a-polymorphism-with-idiopathic-non-obstructive-azoospermia-in-a-south-indian-cohort
#13
Shalaka S Ramgir, Nishu Sekar, Divya Jindam, Abilash V G
Background: Infertility is the inability of a couple to conceive after one and a half years of unprotected sex. Male infertility, which accounts for almost half of infertility cases, is considered as a major problem all over the world. The aim of this study was to investigate the association of CYP1A1 polymorphisms with idiopathic non-obstructive azoospermia in a South Indian cohort. MATERIALS AND METHODS: An experimental study was conducted with idiopathic nonobstructive azoospermia...
October 2017: International Journal of Fertility & Sterility
https://www.readbyqxmd.com/read/28866654/hydroxylation-and-sulfation-of-sex-steroid-hormones-in-inflammatory-liver
#14
Sang R Lee, Seung-Yeon Lee, Sang-Yun Kim, Si-Yun Ryu, Bae-Kuen Park, Eui-Ju Hong
Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450, glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, and O-methylation by catechol O-methyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic inflammatory response in vivo to study their biochemical properties in liver diseases...
September 3, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28865089/impact-of-enzalutamide-and-its-main-metabolite-n-desmethyl-enzalutamide-on-pharmacokinetically-important-drug-metabolizing-enzymes-and-drug-transporters
#15
Johanna Weiss, Jutta Kocher, Corina Mueller, Stephanie Rosenzweig, Dirk Theile
Enzalutamide is a new drug against castration-resistant prostate cancer. Recent data indicate profound induction of drug metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro data on other CYP enzymes, drug conjugating enzymes or drug transporters is scarce. Moreover, mechanisms of induction are poorly investigated and the effects of the active metabolite N-desmethyl enzalutamide are unknown. Using LS180 cells as an induction model and quantitative real-time reverse transcription polymerase chain reaction, our study demonstrated a concentration-dependent induction of CYP1A1, CYP1A2, CYP3A5, CYP3A4, UGT1A3, UGT1A9, ABCB1, ABCC2, and ABCG2 mRNA...
September 1, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28860561/short-chain-fatty-acids-enhance-aryl-hydrocarbon-ah-responsiveness-in-mouse-colonocytes-and-caco-2-human-colon-cancer-cells
#16
Un-Ho Jin, Yating Cheng, Hyejin Park, Laurie A Davidson, Evelyn S Callaway, Robert S Chapkin, Arul Jayaraman, Andrew Asante, Clinton Allred, Evelyn A Weaver, Stephen Safe
Aryl hydrocarbon receptor (AhR) ligands are important for gastrointestinal health and play a role in gut inflammation and the induction of T regulatory cells, and the short chain fatty acids (SCFAs) butyrate, propionate and acetate also induce similar protective responses. Initial studies with butyrate demonstrated that this compound significantly increased expression of Ah-responsive genes such as Cyp1a1/CYP1A1 in YAMC mouse colonocytes and Caco-2 human colon cancer cell lines. Butyrate synergistically enhanced AhR ligand-induced Cyp1a1/CYP1A1 in these cells with comparable enhancement being observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and also microbiota-derived AhR ligands tryptamine, indole and 1,4-dihydroxy-2-naphthoic acid (DHNA)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844589/impact-of-cyp1a1-gstp1-and-xrcc1-genes-polymorphisms-on-toxicity-and-response-to-chemotherapy-in-childhood-acute-lymphoblastic-leukemia
#17
Asmaa Abo-Bakr, Ghada Mossallam, Nevin El Azhary, Hanafy Hafez, Ragia Badawy
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. AIM OF THE WORK: The aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL...
August 22, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/28839203/fine-particulate-matter-2-5-exerted-its-toxicological-effect-by-regulating-a-new-layer-long-non-coding-rna
#18
Qiansheng Huang, Yulang Chi, Junjun Deng, Yiyao Liu, Yanyang Lu, Jinsheng Chen, Sijun Dong
Fine particulate matter (PM2.5) exposure, especially to its organic components, induces adverse health effects on the respiratory system. However, the molecular mechanisms have still not been fully elucidated. Long non-coding RNA (lncRNA) is involved in various physio-pathological processes. In this study, the roles of lncRNA were investigated to reveal the toxicology of PM2.5. Organic extracts of PM2.5 from Nanjing and Shanghai cities were adopted to treat human bronchial epithelial cell lines (BEAS-2B and A549)...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834568/methylated-pahs-and-or-their-metabolites-are-important-contributors-to-the-overall-estrogenic-activity-of-pah-contaminated-soils
#19
Monika M Lam, Magnus Engwall, Michael S Denison, Maria Larsson
In this study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay (VM7Luc4E2-TA). Relative potencies (REPs) were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist ICI182,780 (ICI) and the Ah receptor (AhR) antagonist/CYP1A1 inhibitor α-naphthoflavone (α-NF). Luciferase induction and CYP1A1-dependent EROD-activity were measured to assess if the estrogenic activity was elicited by the compound itself and/or by its metabolites...
August 23, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28827732/genetic-predisposition-to-lung-cancer-comprehensive-literature-integration-meta-analysis-and-multiple-evidence-assessment-of-candidate-gene-association-studies
#20
Junjun Wang, Qingyun Liu, Shuai Yuan, Weijia Xie, Yuan Liu, Ying Xiang, Na Wu, Long Wu, Xiangyu Ma, Tongjian Cai, Yao Zhang, Zhifu Sun, Yafei Li
More than 1000 candidate-gene association studies on genetic susceptibility to lung cancer have been published over the last two decades but with few consensuses for the likely culprits. We conducted a comprehensive review, meta-analysis and evidence strength evaluation of published candidate-gene association studies in lung cancer up to November 1, 2015. The epidemiological credibility of cumulative evidence was assessed using the Venice criteria. A total of 1018 publications with 2910 genetic variants in 754 different genes or chromosomal loci were eligible for inclusion...
August 21, 2017: Scientific Reports
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