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CYP2E1

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https://www.readbyqxmd.com/read/27910729/identification-of-cytochrome-p450s-involved-in-the-metabolism-of-6-benzyl-1-benzyloxymethyl-5-iodouracil-w-1-using-human-recombinant-enzymes-and-rat-liver-microsomes-in-vitro
#1
Ying-Yuan Lu, Hai-Xu Cheng, Xin Wang, Xiao-Wei Wang, Jun-Yi Liu, Pu Li, Ya-Qing Lou, Jun Li, Chuang Lu, Guo-Liang Zhang
1. The aim of this study was to identify the hepatic metabolic enzymes, which involved in the biotransformation of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor (NNRTIs) in rat and human in vitro. 2. The parent drug of W-1 was incubated with RLMs or recombinant CYPs (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, respectively) in the presence or absence of NADPH regenerating system. The metabolites of W-1 were analyzed with liquid chromatography-ion trap-time of flight-mass spectrometry (LC-IT-TOF-MS)...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27896817/lack-of-in-vivo-mutagenicity-of-1-2-dichloropropane-and-dichloromethane-in-the-livers-of-gpt-delta-rats-administered-singly-or-in-combination
#2
Tadashi Hirata, Young-Man Cho, Takeshi Toyoda, Jun-Ichi Akagi, Isamu Suzuki, Akiyoshi Nishikawa, Kumiko Ogawa
1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative agents associated with the development of cholangiocarcinoma in employees working in printing plant in Osaka, Japan. However, few reports have demonstrated an association between these agents and cholangiocarcinoma in rodent carcinogenicity studies. Moreover, the combined effects of these compounds have not been fully elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2-DCP and DCM, alone or combined, in the livers of gpt delta rats...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896399/cytochrome-p450-mediated-metabolism-of-triclosan-attenuates-its-cytotoxicity-in-hepatic-cells
#3
Yuanfeng Wu, Priyanka Chitranshi, Lucie Loukotková, Gonçalo Gamboa da Costa, Frederick A Beland, Jie Zhang, Jia-Long Fang
Triclosan is a widely used broad-spectrum anti-bacterial agent. The objectives of this study were to identify which cytochrome P450 (CYP) isoforms metabolize triclosan and to examine the effects of CYP-mediated metabolism on triclosan-induced cytotoxicity. A panel of HepG2-derived cell lines was established, each of which overexpressed a single CYP isoform, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1...
November 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27890642/protective-effect-of-quercetin-on-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-in-mice-is-mediated-by-modulating-intestinal-microbiota-imbalance-and-related-gut-liver-axis-activation
#4
David Porras, Esther Nistal, Susana Martínez-Flórez, Sandra Pisonero-Vaquero, José Luis Olcoz, Ramiro Jover, Javier González-Gallego, María Victoria García-Mediavilla, Sonia Sánchez-Campos
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27883018/cytotoxic-and-genotoxic-potential-of-food-borne-nitriles-in-a-liver-in-vitro-model
#5
Franziska Kupke, Corinna Herz, Franziska S Hanschen, Stefanie Platz, Grace A Odongo, Simone Helmig, María M Bartolomé Rodríguez, Monika Schreiner, Sascha Rohn, Evelyn Lamy
Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27877172/regulated-inflammation-and-lipid-metabolism-in-colon-mrna-expressions-of-obese-germfree-mice-responding-to-enterobacter-cloacae-b29-combined-with-the-high-fat-diet
#6
Huiying Yan, Na Fei, Guojun Wu, Chenhong Zhang, Liping Zhao, Menghui Zhang
Increased evidences have demonstrated that gut microbiota targeted diet intervention can alleviate obesity and related metabolic disorders. The underlying mechanism of interactions among diet, microbiota, and host still remains unclear. Enterobacter cloacae B29, an endotoxin-producing strain dominated in the gut of a morbidly obese volunteer (weight 174.8 kg, BMI 58.8 kg m(-2)) was isolated and transplanted to germfree mice (inoculated 10(10) cells of B29 per day for 1 week). Using deep mRNA sequencing technology, we compared different gene expression profiles in the colon samples of the germfree mice treated with/without B29 and/or high fat diet (HFD) for 16 weeks and identified 279 differential expressed genes in total, including up-regulated genes Apoa4 (fold change, 2...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27872699/the-effects-of-fenvalerate-on-hepatic-and-cerebral-xenobiotic-metabolizing-enzymes-in-selenium-and-or-iodine-deficient-rats
#7
Aydan Caglayan, Belma Kocer-Gumusel, Pinar Erkekoglu, Filiz Hincal
OBJECTIVES: Particularly in developing countries, selenium and/or iodine deficiencies are encountered and use of pesticides in agriculture are not well-controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has applications against a wide range of pests. This study was designed to evaluate the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme activities in the presence of iodine and/or selenium deficiency on a rat model. MATERIALS AND METHODS: Iodine and/or selenium deficiency was induced by feeding three-week-old Wistar rats with a diet containing <0...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27867264/traditional-herbal-formulas-to-as-treatments-for-musculoskeletal-disorders-their-inhibitory-effects-on-the-activities-of-human-microsomal-cytochrome-p450s-and-udp-glucuronosyltransferases
#8
Seong Eun Jin, Chang-Seob Seo, Hyeun-Kyoo Shin, Hyekyung Ha
OBJECTIVE: The aim of this study was to assess the influence of traditional herbal formulas, including Bangpungtongseong-san (BPTSS; Fangfengtongsheng-san, Bofu-tsusho-san), Ojeok-san (OJS; Wuji-san, Goshaku-san), and Oyaksungi-san (OYSGS; Wuyaoshungi-san, Uyakujyunki-san), on the activities of the human cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs), which are drug-metabolizing enzymes. MATERIALS AND METHODS: The activities of the major human CYP450 isozymes (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were investigated using in vitro fluorescence-based and luminescence-based enzyme assays, respectively...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27865386/factors-associated-with-anti-tb-drug-induced-hepatotoxicity-and-genetic-polymorphisms-in-indigenous-and-non-indigenous-populations-in-brazil
#9
Melissa M Heinrich, Verônica M Zembrzuski, Marcos M Ota, Flavia P Sacchi, Raquel L F Teixeira, Pedro H Cabello Acero, Geraldo Marcelo Cunha, Reinaldo Souza-Santos, Julio Croda, Paulo C Basta
Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865233/cyp2e1-polymorphism-acetylator-profiles-and-drug-induced-liver-injury-incidence-of-indonesian-tuberculosis-patients
#10
Dyah A Perwitasari, Lalu M Irham, Endang Darmawan, Ully A Mulyani, J Atthobari
OBJECTIVE: A polymorphism of CYP2E1 may be directly associated with the development of INH hepatotoxicity. We conducted this study to evaluate the association between polymorphisms of CYP2E1, Isoniazid (INH) concentration and the acetylator status of INH in cases of Indonesian tuberculosis patients with drug-induced liver disease (DILI). METHODS: We conducted our study with a cohort design consisting of 55 Indonesian adult tuberculosis (TB) patients. Acetylating phenotypes were studied in using the metabolic ratio of plasma AcHZ/HZ...
July 2016: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/27830004/ferulic-acid-attenuated-acetaminophen-induced-hepatotoxicity-though-down-regulating-the-cytochrome-p-2e1-and-inhibiting-toll-like-receptor-4-signaling-mediated-inflammation-in-mice
#11
Junhui Yuan, Kuang Ge, Junhuan Mu, Jiang Rong, Li Zhang, Bin Wang, Jingyuan Wan, Gong Xia
Ferulic acid (FA), a phenolic acid which is abundant in vegetables and fruits, has been reported to exert anti-oxidative and anti-inflammatory activities. In the present study, the pharmacological effects and the underlying mechanisms of FA in mice with acetaminophen-induced hepatotoxicity were investigated. Our results revealed that FA pretreatment inhibited the augments of serum aminotransferases in a dose-dependent manner and attenuated the hepatic histopathological abnormalities and hepatocellular apoptosis in acetaminophen (APAP) exposed mice...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27828666/maternal-protein-restriction-during-lactation-modulated-the-expression-and-activity-of-rat-offspring-hepatic-cyp1a1-cyp1a2-cyp2b1-cyp2b2-and-cyp2e1-during-development
#12
N Meireles Da Costa, S B C Visoni, I L Dos Santos, T C Barja-Fidalgo, L F Ribeiro-Pinto
Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation...
2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27825756/carvacrol-attenuates-acute-kidney-injury-induced-by-cisplatin-through-suppression-of-erk-and-pi3k-akt-activation
#13
Iva Potočnjak, Robert Domitrović
We investigated the mechanisms of renoprotective effects of carvacrol, a monoterpenoid compound, against cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 1, 3, and 10 mg carvacrol/kg body weight for two days, 48 h after intraperitoneal injection of CP (13 mg/kg). Four days after CP administration, renal oxidative stress was evidenced by increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1), and heme oxygenase-1 (HO-1). CP treatment increased the expression of phosphorylated nuclear factor-kappaB (p-NF-κB) p65 and tumor necrosis factor-alpha (TNF-α) in kidneys, suggesting inflammatory response...
November 4, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27816004/diazepam-influences-urinary-bioindicator-of-occupational-toluene-exposure
#14
Alberto Thalison Silveira, Ana Carolina Campos Albuquerque, José Salvador Lepera, Isarita Martins
In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0...
December 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27812602/a-non-hepatotropic-parasite-infection-increases-mortality-in-the-acetaminophen-induced-acute-liver-failure-murine-model-possible-roles-for-il-5-and-il-6
#15
Marco A De León-Nava, Carolina Álvarez-Delgado, Luis Donis-Maturano, Joselin Hernández-Ruiz, Aaron N Manjarrez-Reyna, Edgar Cruz-Avilés, Sonia Leon-Cabrera, Jorge Morales-Montor, José M Fragoso, Galileo Escobedo
We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died...
October 31, 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/27806083/integrated-multiple-omics-data-reveal-subtypes-of-hepatocellular-carcinoma
#16
Gang Liu, Chuanpeng Dong, Lei Liu
Hepatocellular carcinoma is one of the most heterogeneous cancers, as reflected by its multiple grades and difficulty to subtype. In this study, we integrated copy number variation, DNA methylation, mRNA, and miRNA data with the developed "cluster of cluster" method and classified 256 HCC samples from TCGA (The Cancer Genome Atlas) into five major subgroups (S1-S5). We observed that this classification was associated with specific mutations and protein expression, and we detected that each subgroup had distinct molecular signatures...
2016: PloS One
https://www.readbyqxmd.com/read/27800121/erectile-dysfunction-drugs-changed-the-protein-expressions-and-activities-of-drug-metabolising-enzymes-in-the-liver-of-male-rats
#17
Salah A Sheweita, Mona Wally, Mostafa Hassan
Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27795667/chronic-ethanol-exposure-effects-on-vitamin-d-levels-among-subjects-with-alcohol-use-disorder
#18
Olalekan Ogunsakin, Tete Hottor, Ashish Mehta, Maureen Lichtveld, Michael McCaskill
Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37...
2016: Environmental Health Insights
https://www.readbyqxmd.com/read/27793734/reversal-of-ethanol-induced-hepatotoxicity-by-cinnamic-and-syringic-acids-in-mice
#19
Sheng-Lei Yan, Zhi-Hong Wang, Hsiu-Fang Yen, Yi-Ju Lee, Mei-Chin Yin
Ethanol was used to induce acute hepatotoxicity in mice. Effects of cinnamic acid (CA) and syringic acid (SA) post-intake for hepatic recovery from alcoholic injury was investigated. Ethanol treated mice were supplied by CA or SA at 40 or 80 mg/kg BW/day for 5 days. Results showed that ethanol stimulated protein expression of CYP2E1, p47(phox), gp91(phox), cyclooxygenase-2 and nuclear factor kappa B in liver. CA or SA post-intake restricted hepatic expression of these molecules. Ethanol suppressed nuclear factor erythroid 2-related factor (Nrf2) expression, and CA or SA enhanced Nrf2 expression in cytosolic and nuclear fractions...
October 25, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27787372/does-cyp2e1-rsai-psti-polymorphism-confer-head-and-neck-carcinoma-susceptibility-a-meta-analysis-based-on-43-studies
#20
Xianlu Zhuo, Jue Song, Jian Liao, Wei Zhou, Huiping Ye, Qi Li, Zhaolan Xiang, Xueyuan Zhang
BACKGROUND: Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result. METHODS: Eligible studies up to Nov 2015 were retrieved and screened...
October 2016: Medicine (Baltimore)
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