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Jeong-Wook Choi, In-Hye Kim, Young-Min Kim, Min-Kyeong Lee, Youn-Hee Choi, Taek-Jeong Nam
The present study investigated the protective effect of Pyropia yezoensis glycoprotein (PYGP) against chronic ethanol consumption‑mediated hepatotoxicity in rats. Male Sprague-Dawley rats (n=20; 6 weeks old) were randomly divided into four groups. The rats in each group were treated for 30 days with the following: i) CON group, distilled water only; ii) EtOH group, 20% ethanol 3.7 g/kg/BW; iii) EtOH+150 group, 20% ethanol 3.7 g/kg/BW+PYGP 150 mg/kg/BW; iv) EtOH+300 group, 20% ethanol 3.7 g/kg/BW+PYGP 300 mg/kg/BW...
October 11, 2016: Molecular Medicine Reports
Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Murali Ganesan, Larisa Y Poluektova, Dean J Tuma, Kusum K Kharbanda, Natalia A Osna
BACKGROUND: Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and worsens disease outcomes. The exact reasons are not clear yet, but they might be partially attributed to the ability of alcohol to further suppress the innate immunity. Innate immunity is known to be already decreased by HCV in liver cells. METHODS: In this study, we aimed to explore the mechanisms of how alcohol metabolism dysregulates IFNα signaling (STAT1 phosphorylation) in HCV(+) hepatoma cells...
September 26, 2016: Alcoholism, Clinical and Experimental Research
Janneke G F Hogervorst, Piet A van den Brandt, Roger W L Godschalk, Frederik-Jan van Schooten, Leo J Schouten
It is unclear whether the association between dietary acrylamide intake and endometrial cancer risk as observed in some epidemiological studies reflects a causal relationship. We aimed at clarifying the causality by analyzing acrylamide-gene interactions for endometrial cancer risk. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was selected for a case cohort analysis approach. Acrylamide intake of subcohort members and endometrial cancer cases (n = 315) was assessed with a food frequency questionnaire...
October 7, 2016: Scientific Reports
Xianbao Shi, Brianna Mackie, Gang Zhang, Shuman Yang, Yonggui Song, Dan Su, Yali Liu, Lina Shan
Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs), rabbits (RAMs), and dogs (DLMs)...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Tadatoshi Tanino, Akira Komada, Koji Ueda, Toru Bando, Yukie Nojiri, Yukari Ueda, Eiichi Sakurai
Type 1 allergic diseases are characterized by elevated production of specific immunoglobulin E (IgE) for each antigen and have become a significant health problem worldwide. This study investigated the effect of IgE-mediated allergy on drug pharmacokinetics. To further understand differential suppression of hepatic cytochrome P450 (CYP) activity, we examined the inhibitory effect of nitric oxide (NO), a marker of allergic conditions. Seven days after primary or secondary sensitization (PS7 and SS7, respectively), hepatic CYP1A2, CYP2C, CYP2E1 and CYP3A activities were decreased to 45%-75% of the corresponding control, however, CYP2D activity was not downregulated...
September 30, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Shilong Zhong, Weichao Han, Chuqi Hou, Junjin Liu, Lili Wu, Menghua Liu, Zhi Liang, Haoming Lin, Lili Zhou, Shuwen Liu, Lan Tang
Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs...
September 28, 2016: AAPS Journal
Nobuhiro Wada, Satoru Yamanaka, Junko Shibato, Randeep Rakwal, Satoshi Hirako, Yuzuru Iizuka, Hyounju Kim, Akiyo Matsumoto, Ai Kimura, Fumiko Takenoya, Genta Yasunaga, Seiji Shioda
This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+ WME) supplemented diet for 26 weeks were subjected to four behavioral tests - open field, Y-maze, new object recognition, and water-filled multiple T-maze - to examine effects on learning and memory...
December 2016: Genomics Data
Satish Kumar Bedada, Praveen Kumar Boga
1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers. 2. An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20 mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC...
September 27, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Yuko Shimamura, Misako Iio, Tomoko Urahira, Shuichi Masuda
BACKGROUND: The recent finding of acrylamide (AA), which is formed in cooked foods, has raised human health concerns. AA is metabolized by CYP2E1 to glycidamide (GA). GA forms DNA adducts. In this study, we examined the inhibitory effects of wasabi (Japanese horseradish, Wasabia japonica) roots and leaves as well as their active component, allyl isothiocyanate (AIT), on the formation and genotoxicity of AA. RESULTS: AA formation (51.8 ± 4.2 µg/kg) was inhibited with ≥2 mg/mL of AIT...
September 27, 2016: Journal of the Science of Food and Agriculture
Wei Li, Meng-Han Yan, Ying Liu, Zhi Liu, Zi Wang, Chen Chen, Jing Zhang, Yin-Shi Sun
Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time...
2016: Nutrients
Kenichi Kakino, Chikako Kiyohara, Takahiko Horiuchi, Yoichi Nakanishi
BACKGROUND: Cytochrome P450 2E1 (CYP2E1) and catechol-O-methyltransferase (COMT) genes may contribute to susceptibility to lung cancer because of their critical involvement in mechanisms of carcinogenesis. MATERIALS AND METHODS: We evaluated the role of CYP2E1 rs2031920 and COMT rs4680 in a case-control study involving 462 lung cancer cases and 379 controls in Japanese. Logistic regression was used to assess adjusted odds ratios (OR) and 95% confidence intervals (CI)...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Hansi Jia, Chiteng Zhang, Hansruedi Glatt, Yungang Liu
The standard procedure for the micronucleus test in cell lines requires a short exposure (≤0.5 cell cycle) to the test compounds followed by a long recovery (≥1.5 cell cycle), and in case of negative or equivocal results, a second test with extended exposure (≥2 cell cycles) without or with a recovery time. In general the two procedures are advantageous for detecting clastogens and aneugens, respectively. However, whether the recommended procedures apply to micronucleus tests with promutagens in cell lines genetically engineered for expressing biotransformation enzymes has not been identified...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Peiyao Fu, Fan Yang, Bo Li, Biao Zhang, Lianyue Guan, Jiyao Sheng, Yanshuo Ye, Zhanpeng Wang, Peidong Li, Li Xu, Liangjian Zou, Wei Li
BACKGROUND: The CYP2E1 protein is a monooxygenase with certain polymorphisms linked to liver cancer. However, results from individual studies remain controversial. AIMS: To evaluate CYP2E1 polymorphisms in liver carcinogenesis through meta-analysis. METHODS: All studies about CYP2E1 polymorphisms and liver cancer were retrieved from seven major databases. Original data from each study were pooled and re-analyzed. RESULTS: Total of 16 articles with 4862 cases were selected, including 1820 cases of liver cancer and 3042 cases of controls...
August 18, 2016: Digestive and Liver Disease
Zhi-Hui Zhang, Xiao-Qian Liu, Cheng Zhang, Wei He, Hua Wang, Yuan-Hua Chen, Xiao-Jing Liu, Xi Chen, De-Xiang Xu
Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice...
2016: Scientific Reports
Chao-Feng Hu, Li-Ping Sun, Qin-He Yang, Da-Xiang Lu, Sen Luo
OBJECTIVE: To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanolinduced lipid deposition in human L02 hepatocytes. METHODS: L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyltetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry...
September 10, 2016: Chinese Journal of Integrative Medicine
Ayse S Karadag, Tuğba K Uzunçakmak, Seyma Ozkanli, Serpil Oguztuzun, Busra Moran, Ozge Akbulak, Emin Ozlu, Itir E Zemheri, Serap G Bilgili, Necmettin Akdeniz
Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining...
September 9, 2016: International Journal of Dermatology
Suraphan Panyod, Wei-Kai Wu, Chi-Tang Ho, Kuan-Hung Lu, Chun-Ting Liu, Yung-Lin Chu, Yi-Syuan Lai, Wei-Cheng Chen, Yu-En Lin, Shih-Hang Lin, Lee-Yan Sheen
This study investigated the liver-protective effects of allicin, an active compound in fresh garlic, against alcoholic fatty liver disease (AFLD) and liver inflammation. Its effects were investigated in an AFLD model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Allicin (5 and 20 mg/kg bw/day) was orally administered daily in the AFLD mice for 4 weeks. The results indicate that allicin promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels (p < 0...
September 28, 2016: Journal of Agricultural and Food Chemistry
Bruno Christian Koehler, Tatjana Arslic-Schmitt, Theresa Peccerella, Anna-Lena Scherr, Henning Schulze-Bergkamen, Thomas Bruckner, Georg Gdynia, Dirk Jäger, Sebastian Mueller, Helmut Bartsch, Helmut K Seitz
BACKGROUND: Chronic alcohol consumption is a risk factor for colorectal cancer. The mechanisms by which ethanol (EtOH) exerts its carcinogenic effect on the colorectal mucosa are not clear and may include oxidative stress with the action of reactive oxygen species (ROS) generated through EtOH metabolism via cytochrome P4502E1 (CYP2E1) leading to carcinogenic etheno-DNA adducts. ROS may also induce apoptosis. However, the effect of chronic EtOH consumption on CYP2E1, etheno-DNA adducts as well as anti-apoptotic proteins in the colorectal mucosa of heavy drinkers without colorectal inflammation is still not known...
October 2016: Alcoholism, Clinical and Experimental Research
Aimee L Katen, Caitlin G Chambers, Brett Nixon, Shaun D Roman
Acute acrylamide exposure in male rodents results in reduced reproductive performance and dominant lethality. However, the reproductive effects of low dose chronic exposure, which better reflects the nature of human exposure, remain far less certain. Human dietary consumption of acrylamide has been estimated at an average of 1-4 µg/kg bw/day. In order to simulate this exposure, male mice were provided with acrylamide (1 µg/ml) via their drinking water continuously for six months, which was equivalent to a human dose of 10...
August 31, 2016: Biology of Reproduction
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