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Marilia N Siebert, Jacó J Mattos, Clei E Piazza, Daína de Lima, Carlos Henrique A M Gomes, Cláudio M R de Melo, Afonso C D Bainy
Cytochrome P450 family 1 (CYP1) is involved in polycyclic aromatic hydrocarbons (PAHs) biotransformation. PAHs can induce CYP1 protein expression and enzyme activity, the latter being usually quantified as 7-ethoxyresorufin O-deethylase activity (EROD). The aim of this study was to characterize EROD activity in the bivalve mollusk Crassostrea brasiliana. EROD activity was evaluated in cytosolic and microsomal fractions of gills, digestive gland and mantle of C. brasiliana. No EROD activity was detected in mantle, but it was present in microsomal fraction of gills and digestive gland with NADPH as coenzyme...
October 18, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Kai Sheng, Jiahuan Lu
Quinones that exist in ambient particulate matter (PM) are hypothesized to be associated with adverse health effects through the generation of reactive oxygen species (ROS). However, the impacts of the quinones on the inflammatory processes have yet to be clearly understood. In this study, we examined the oxidative potentials and biological effects of typical airborne quinones in the human lung epithelial A549 cells. Significant change of redox status, loss of mitochondrial membrane potentials (△Ψ) and increase of superoxide dismutase (SOD) activity were induced by exposure to quinones...
October 21, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
Tsuyoshi Chiba, Keiko Noji, Shohei Shinozaki, Sachina Suzuki, Keizo Umegaki, Kentaro Shimokado
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is associated with impaired liver function, and resveratrol could suppress NAFLD progression. This study examined the effects of NAFLD on the expression of major cytochrome P450 (CYP) subtypes in the liver and whether the expression could be attenuated by resveratrol. METHODS: C57BL/6 mice (male, 10 weeks of age) were fed a high-fat and high-sucrose (HFHS) diet to induce NAFLD. Major Cyp subtype mRNA expression in the liver was measured by real-time RT-PCR...
October 19, 2016: Journal of Pharmacy and Pharmacology
Zoraida Verde, Catalina Santiago, Luis Miguel Chicharro, Luis Reinoso-Barbero, Alejandro Tejerina, Fernando Bandrés, Félix Gómez-Gallego
INTRODUCTION: Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1, CYP2A6) or in DNA repair (XRCC1, APEX1, XRCC3 and XPD) in breast cancer development. METHODS: We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women...
October 14, 2016: International Journal of Molecular Sciences
Sedar Karakurt
Expression of a drug and xenobiotic metabolizing enzymes, cytochrome P450s (CYPs), and antioxidant enzymes can be modulated by various factors. The flavonoid rutin was investigated for its anti-carcinogen and protective effects as well as modulatory action on CYPs and phase II enzymes in human hepatocellular carcinoma cells. Rutin inhibited proliferation of HEPG2 cells in a dose-dependent manner with the IC50 value of 52.7 μmol L-1 and invasion of HEPG2 cells (21.6 %, p = 0.0018) and colony formation of those invaded cells (57...
December 1, 2016: Acta Pharmaceutica
Zhiying Luo, Xi Li, Mingfeng Zhu, Jie Tang, Zhi Li, Xinming Zhou, Guobao Song, Zhaoqian Liu, Honghao Zhou, Wei Zhang
BACKGROUND: The variation among patients in warfarin response complicated the management of warfarin therapy, improper therapeutic dose usually result in serious adverse events. OBJECTIVE: A two-stage extreme phenotype strategy was conducted to discover novel warfarin dose associated mutations in heart valve replacement (HVR) patients. PATIENTS/METHOD: A total of 1617 warfarin stable dose (WSD) patients were enrolled and divided randomly into two cohorts...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Martina Štěpánková, Kristýna Krasulová, Aneta Dořičáková, Ondřej Kurka, Pavel Anzenbacher, Zdeněk Dvořák
Dihydropyridine calcium channel blockers (CCBs) are used as anti-hypertensives and in the treatment of angina pectoris. Structurally, CCBs have at least one chiral center in the molecule, thereby existing in two or more different enantiomers. In the current paper we examined effects of benidipine, felodipine and isradipine enantiomers on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450. All CCBs dose-dependently activated aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), as revealed by gene reporter assays...
October 9, 2016: Toxicology Letters
Sreekanth C Narayanapillai, Shang-Hsuan Lin, Pablo Leitzman, Pramod Upadhyaya, Carolyn J Baglole, Chengguo Xing
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key carcinogen responsible for tobacco smoke-induced lung carcinogenesis. Among DNA damages caused by NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), O6-methylguanine (O6-mG) is likely the most carcinogenic in A/J mice. Results of our previous studies showed that O6-mG and other NNAL-derived DNA damages were preferentially reduced in the lung of female A/J mice upon the dietary treatment with dihydromethysticin (DHM), a promising lung cancer chemopreventive agent from kava...
October 11, 2016: Chemical Research in Toxicology
Mohd Usman Mohd Siddique, Glen J P McCann, Vinay Sonawane, Neill Horley, Ibidapo Steven Williams, Prashant Joshi, Sandip B Bharate, Venkatesan Jayaprakash, Barij N Sinha, Bhabatosh Chaudhuri
Highly selective CYP1B1 inhibitors have potential in the treatment of hormone-induced breast and prostate cancers. Mimicry of potent and selective CYP1B1 inhibitors, α-naphthoflavone and stilbenes, revealed that two sets of hydrophobic clusters suitably linked via a polar linker could be implanted into a new scaffold 'biphenyl ureas' to create potentially a new class of CYP1B1 inhibitors. A series of sixteen biphenyl ureas were synthesized and screened for CYP1B1 and CYP1A1 inhibition in Sacchrosomes™, yeast-derived recombinant microsomal enzymes...
September 26, 2016: Organic & Biomolecular Chemistry
Hesbon Z Amenya, Chiharu Tohyama, Seiichiroh Ohsako
The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1)...
October 7, 2016: Scientific Reports
A M Barbosa, S R de Souza, A B Frare, R C Costa E Silva, I R da Costa, K S Freitas E Silva, C L Ribeiro Júnior, B M Bordin, K K V O Moura
Endometriosis is a disease that affects 10 to 15% of the women of reproductive age. It is characterized by the presence of endometrial-like tissues outside of the uterus. Some definitions claim that the functional ectopic tissue is sensitive to the action of hormones. Severity of endometriosis is defined according to a system proposed by the American Society for Reproductive Medicine, which is based on laparoscopic findings. A large number of genetic polymorphisms has been reported for CYP1A1, the gene that is responsible for enzymes involved in stage I detoxification of xenobiotics; this gene is located at 15q22-24, and encodes an isoenzyme that catalyzes the oxidation of polycyclic aromatic hydrocarbons present in phenolic compounds and epoxides...
August 26, 2016: Genetics and Molecular Research: GMR
Sabina Ranjit, Narasimha M Midde, Namita Sinha, Benjamin J Patters, Mohammad A Rahman, Theodore J Cory, P S S Rao, Santosh Kumar
BACKGROUND: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. METHODS: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity...
2016: PloS One
Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Atanas Georgiev Atanasov, Verena Maria Dirsch, Waranya Chatuphonprasert, Sivio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Rainer de Martin, Zsuzsanna Bago-Horvath, Georg Krupitza, Walter Jäger
A causal link between overexpression of aryl hydrocarbon receptor (AHR) and its target cytochrome P450 1A1 (CYP1A1) and metastatic outgrowth of various cancer entities has been established. Nevertheless, the mechanism how AHR/CYP1A1 support metastasis formation is still little understood. In vitro we discovered a potential mechanism facilitating tumour dissemination based on the production of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Utilising a three-dimensional lymph endothelial cell (LEC) monolayer & MDA-MB231 breast cancer cell spheroid co-culture model in combination with knock-down approach allowed elucidation of the molecular/biochemical basis of AHR/CYP1A1-induced tumour breaching through the LEC barrier...
September 27, 2016: Human Molecular Genetics
Shi-Yuan Wang, Qi Zhang, Xiang Zhang, Pei-Quan Zhao
AIM: To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis (LCA) in Chinese. METHODS: LCA subjects and their families were retrospectively collected from 2013 to 2015. Firstly, whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found, and then homozygous sites was selected, candidate sites were annotated, and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant (SIFT), Polyphen-2, Mutation assessor, Condel, and Functional Analysis through Hidden Markov Models (FATHMM)...
2016: International Journal of Ophthalmology
B J Hughes, J Thomas, A M Lynch, S J Borghoff, S Green, T Mensing, S S Sarang, M J LeBaron
In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F1 mice at 1800 ppm. A DNA reactive Mode-of-Action (MOA) for this liver tumor response is not supported by the evidence as MIBK and its major metabolites lack genotoxicity in both in vitro and in vivo studies. Constitutive androstane receptor (CAR) nuclear receptor-mediated activation has been hypothesized as the MOA for MIBK-induced mouse liver tumorigenesis...
September 21, 2016: Regulatory Toxicology and Pharmacology: RTP
Masashi Sekimoto, Haruna Sumi, Takuomi Hosaka, Takashi Umemura, Akiyoshi Nishikawa, Masakuni Degawa
The ability of nine cooked food-derived heterocyclic aromatic amines (HCAs), such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methylpyrido[12-a:3',2'-d]imidazole (Glu-P-1), 2-amino-pyrido[12-a:3',2'-d]imidazole hydrochloride (Glu-P-2), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP), to activate human aryl hydrocarbon receptor (hAhR) was examined using a HepG2-A10 cell line, which has previously established from human hepatocarcinoma-derived HepG2 cells for use in hAhR-based luciferase reporter gene assays...
September 16, 2016: Food and Chemical Toxicology
Li Lei, Xinqiang Shen, Mei Jiang
We studied the effect of water accommodated fractions (WAF) of 0# diesel and crude oil on ethoxy resorufin o-deethylase (EROD) activity and CYP1A1 mRNA expression quantity in the liver of Sparus macrocephlus. We found that there were some differences in the EROD activity and CYP1A1 mRNA induction between these two petroleum hydrocarbons. Both the EROD activity and CYP1A1 mRNA expression of fish exposed to 0# diesel WAF were higher than those of crude oil WAF fish. The EROD activities and CYP1A1 mRNA expressions in the livers 0# diesel WAF exposed group declined faster than those of crude oil WAF and the recovery of EROD activity and CYP1A1 mRNA expression in the crude oil group was higher than that of 0# diesel group...
September 15, 2016: Ecotoxicology and Environmental Safety
Ume-Kulsoom Shah, Anna L Seager, Paul Fowler, Shareen H Doak, George E Johnson, Sharon J Scott, Andrew D Scott, Gareth J S Jenkins
Benzo[a]pyrene (B[a]P) is a known genotoxin and carcinogen, yet its genotoxic response at low level exposure has not been determined. This study was conducted to examine the interplay of dose and metabolic capacity on genotoxicity of B[a]P. Investigating and better understanding the biological significance of low level chemical exposures will help improve human health risk assessments. The genotoxic and mutagenic effects of B[a]P were investigated using human cell lines (AHH-1, MCL-5, TK6 and HepG2) with differential expression of the CYP450 enzymes CYP1A1, 1B1 and1A2 involved in B[a]P metabolism...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Yunxia Zhao, Ye Hou, Fei Liu, An Liu, Lu Jing, Changzhi Zhao, Yu Luan, Yuanxin Miao, Shuhong Zhao, Xinyun Li
Feed efficiency (FE) is essential for pig production. In this study, 300 significantly differentially expressed (DE) transcripts, including 232 annotated genes, 28 cis- natural antisense transcripts (cis-NATs), and 40 lncRNAs, were identified between the liver of Yorkshire pigs with extremely high and low FE. Among these transcripts, 25 DE lncRNAs were significantly correlated with 125 DE annotated genes at a transcriptional level. These DE genes were primarily enriched in Vitamin A (VA), fatty acid, and steroid hormone metabolism...
September 15, 2016: G3: Genes—Genomes—Genetics
Weiru Jiang, Xiangge Tian, Yan Wang, Zheng Sun, Peipei Dong, Chao Wang, Xiaokui Huo, Baojing Zhang, Shanshan Huang, Sa Deng, Xiaobo Wang, Xiaochi Ma
Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism...
September 12, 2016: Toxicology Letters
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