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https://www.readbyqxmd.com/read/28728133/zebrafish-have-an-ethanol-inducible-hepatic-4-nitrophenol-hydroxylase-that-is-not-cyp2e1-like
#1
Jessica H Hartman, Jordan S Kozal, Richard T Di Giulio, Joel N Meyer
Zebrafish are an attractive model organism for toxicology; however, an important consideration in translating between species is xenobiotic metabolism/bioactivation. CYP2E1 metabolizes small hydrophobic molecules, e.g. ethanol, cigarette smoke, and diesel exhaust components. CYP2E1 is thought to only be conserved in mammals, but recent reports identified homologous zebrafish cytochrome P450s. Herein, ex vivo biochemical measurements show that unlike mammals, zebrafish possess a low-affinity 4-nitrophenol hydroxylase (Km ∼0...
July 10, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28718679/salvia-fruticosa-modulates-mrna-expressions-and-activity-levels-of-xenobiotic-metabolizing-cyp1a2-cyp2e1-nqo1-gpx-and-gst-enzymes-in-human-colorectal-adenocarcinoma-ht-29-cells
#2
Ahmet Altay, Faruk Bozoğlu
Natural products have gained considerable interests because of their use in some industrial areas including nutrition, cosmetic, pharmacy, and medicine. Salvia fruticosa M. (Lamiaceae) is known for its antioxidant, antimicrobial, and antiproliferative activities. Phase I xenobiotic metabolizing enzymes, CYP1A2 and CYP2E1, produce reactive metabolites which are eliminated by the action of phase II enzymes, NQO1, GPx, and glutathione S-transferases (GSTs). In this study, in vitro modulatory effects of S. fruticosa and its major phenolic compound rosmarinic acid (RA) on CYP1A2, CYP2E1, NQO1, GPx, and GSTm1 mRNA expressions and enzyme activities of GPx and GSTs were investigated in HT-29 cells...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28713991/pien-tze-huang-gan-bao-attenuates-carbon-tetrachloride%C3%A2-induced-hepatocyte-apoptosis-in-rats-associated-with-suppression-of-p53-activation-and-oxidative-stress
#3
Jinyan Zhao, Yuchen Zhang, Yun Wan, Haixia Hu, Zhenfeng Hong
Pien Tze Huang Gan Bao (PZH‑GB), a traditional Chinese medicine, has been used for thousands of years as a protective remedy effective against liver injury induced by excessive alcohol and smoking. The present study aimed to evaluate the protective effects and potential mechanisms of PZH‑GB against carbon tetrachloride (CCl4)‑induced hepatic injury. Rats were pre‑treated with silymarin (50 mg/kg) or different doses of PZH‑GB (150, 300 or 600 mg/kg) orally administered for 7 days. At the end of treatment, the rats were intraperitoneally injected with CCl4, or control rats received a corn oil injection...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28701180/influence-of-genetic-variants-on-toxicity-to-anti-tubercular-agents-a-systematic-review-and-meta-analysis-protocol
#4
Marty Richardson, Jamie Kirkham, Kerry Dwan, Derek Sloan, Geraint Davies, Andrea Jorgensen
BACKGROUND: Tuberculosis patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase the risk of experiencing such toxicity events. Many pharmacogenetic studies have investigated the association between genetic variants and anti-tuberculosis drug-related toxicity events, and several meta-analyses have synthesised data from these studies, although conclusions from these meta-analyses are conflicting...
July 13, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28688179/resveratrol-attenuates-excessive-ethanol-exposure-induced-insulin-resistance-in-rats-via-improving-nad-nadh-ratio
#5
Gang Luo, Bingqing Huang, Xiang Qiu, Lin Xiao, Ning Wang, Qin Gao, Wei Yang, Liping Hao
SCOPE: Resveratrol has been shown to improve insulin resistance via activating the NAD(+) -dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD(+) /NADH and SIRT1 expression. METHODS AND RESULTS: Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 0...
July 8, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28681206/protective-effect-of-ganoderma-lucidum-polysaccharide-against-carbon-tetrachloride-induced-hepatic-damage-in-precision-cut-carp-liver-slices
#6
Yingjuan Liu, Chunyun Zhang, Jinliang Du, Rui Jia, Liping Cao, Galina Jeney, Hiroki Teraoka, Pao Xu, Guojun Yin
The aim of the present study was to investigate the protective effects of Ganoderma lucidum polysaccharide (GLPS) against carbon tetrachloride (CCl4)-induced hepatotoxicity in vitro in common carp. Precision-cut liver slices (PCLSs), which closely resemble the organ from which they are derived, were employed as an in vitro model system. GLPS (0.1, 0.3, and 0.6 mg/ml) was added to PCLS culture system before the exposure to 12 mM CCl4. The supernatants and slices were collected to detect molecular and biochemical responses to CCl4 and PCLS treatments...
July 5, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28677809/inhibition-of-aldose-reductase-ameliorates-alcoholic-liver-disease-by-activating-ampk-and-modulating-oxidative-stress-and-inflammatory-cytokines
#7
Changxuan Shi, Yuanfang Wang, Jing Gao, Si Chen, Xiangqian Zhao, Chengchao Cai, Chang Guo, Longxin Qiu
Aldose reductase (AR) expression is elevated in the livers of patients with alcoholic liver diseases. However, the role of AR in the development of alcoholic liver diseases remains unclear. The aim of the present study was to determine the effect of AR inhibition on ethanol‑induced hepatosteatosis in vivo and in vitro, and to identify possible underlying molecular mechanisms. Alcoholic fatty livers were induced in C57BL/6 mice by feeding the mice with Lieber‑DeCarli liquid diets. The expression of AR protein was elevated in the liver tissue of C57BL/6 mice fed with an ethanol diet and in mouse AML12 liver cells exposed to ethanol...
June 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28673560/down-regulation-of-the-expression-of-alcohol-dehydrogenase-4-and-cyp2e1-by-the-combination-of-%C3%AE-endosulfan-and-dioxin-in-heparg-human-cells
#8
Eléonore A Attignon, Emilie Distel, Béatrice Le-Grand, Alix F Leblanc, Robert Barouki, Eliandre de Oliveira, Martine Aggerbeck, Etienne B Blanc
Pesticides and other persistent organic pollutants are considered as risk factors for liver diseases. We treated the human hepatic cell line HepaRG with both 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and the organochlorine pesticide, α-endosulfan, to evaluate their combined impact on the expression of hepatic genes involved in alcohol metabolism. We show that the combination of the two pollutants (25nM TCDD and 10μM α-endosulfan) led to marked decreases in the amounts of both the mRNA (up to 90%) and protein (up to 60%) of ADH4 and CYP2E1...
June 30, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28670854/honokiol-attenuates-diet-induced-nonalcoholic-steatohepatitis-by-regulating-macrophage-polarization-through-activating-ppar%C3%AE
#9
Xueqing Zhong, Hailin Liu
BACKGROUND AND AIM: Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. This study aimed to investigate whether honokiol could prevent NASH induced by high cholesterol and high fat (CL) diet in mice and the possible mechanism involved. METHODS: Mice were fed with CL diet for 12 weeks to establish a NASH model, honokiol (0.02% w/w in diet) was added to evaluate its effect on NASH. Murine peritoneal macrophages, RAW264.7 and ANA-1 cells were used to explore the possible mechanisms of honokiol on macrophage polarization...
July 2, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28668488/glycyrrhetinic-acid-prevents-acetaminophen-induced-acute-liver-injury-via-the-inhibition-of-cyp2e1-expression-and-hmgb1-tlr4-signal-activation-in-mice
#10
Genling Yang, Li Zhang, Li Ma, Rong Jiang, Ge Kuang, Ke Li, Hongtao Tie, Bin Wang, Xinyu Chen, Tianjun Xie, Xia Gong, Jingyuan Wan
Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored...
June 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28667748/combined-catalase-and-adh-inhibition-ameliorates-ethanol-induced-myocardial-dysfunction-despite-causing-oxidative-stress-in-conscious-female-rats
#11
Fanrong Yao, Abdel A Abdel-Rahman
BACKGROUND: Ethanol-evoked oxidative stress, which contributes to myocardial dysfunction in proestrus rats, is mediated by increases in NADPH oxidase activity, malondialdehyde (MDA) and ERK1/2 phosphorylation. Whether these biochemical responses, which are triggered by alcohol-derived acetaldehyde in non-cardiac tissues, occur in proestrus rats' hearts remains unknown. Therefore, we elucidated the roles of alcohol dehydrogenase (ADH), cytochrome P4502E1 (CYP2E1) and catalase, which catalyze alcohol oxidation to acetaldehyde, in these alcohol-evoked biochemical and hemodynamic responses in proestrus rats...
July 1, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28663312/race-gender-and-genetic-polymorphism-contribute-to-variability-in-acetaminophen-pharmacokinetics-metabolism-and-protein-adduct-concentrations-in-healthy-african-american-and-european-american-volunteers
#12
Michael H Court, Zhaohui Zhu, Gina Masse, Su X Duan, Laura P James, Jerold S Harmatz, David J Greenblatt
Over 30 years ago, black Africans from Kenya and Ghana were shown to metabolize acetaminophen faster by glucuronidation and slower by oxidation compared with white Scottish Europeans. The objectives of this study were to determine whether similar differences exist between African-Americans and European-Americans, and to identify genetic polymorphisms that could explain these potential differences. Acetaminophen plasma pharmacokinetics and partial urinary metabolite clearances via glucuronidation, sulfation, and oxidation were determined in healthy African-Americans (18 men, 23 women) and European-Americans (34 men, 20 women) following a one-gram oral dose...
June 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28657402/in-vitro-evaluation-of-the-inhibition-and-induction-potential-of-olaparib-a-potent-poly-adp-ribose-polymerase-inhibitor-on-cytochrome-p450
#13
Alex McCormick, Helen Swaisland, Venkatesh Pilla Reddy, Maria Learoyd, Graeme Scarfe
1. In vitro studies were conducted to evaluate potential inhibitory and inductive effects of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, on cytochrome P450 (CYP) enzymes. Inhibitory effects were determined in human liver microsomes (HLM); inductive effects were evaluated in cultured human hepatocytes. 2. Olaparib did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2D6 or CYP2E1 and caused slight inhibition of CYP2C9, CYP2C19 and CYP3A4/5 in HLM up to a concentration of 100 µM. However, olaparib (17‒500 µM) inhibited CYP3A4/5 with an IC50 of 119 µM...
June 28, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28650933/cyp2e1-gene-polymorphisms-related-to-the-formation-of-coronary-artery-lesions-in-kawasaki-disease
#14
Ling-Sai Chang, Yu-Wen Hsu, Chien-Chang Lu, Mao-Hung Lo, Kai-Sheng Hsieh, Sung-Chou Li, Wei-Chiao Chang, Ho-Chang Kuo
BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between Cytochrome P450, Family 2, Subfamily E, and Polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected six tag single-nucleotide polymorphisms (tSNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CAL)...
June 23, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28633598/metabolism-of-inhaled-methylethylketone-in-rats
#15
Frédéric Cosnier, Stéphane Grossmann, Hervé Nunge, Céline Brochard, Samuel Muller, Anne-Marie Lambert-Xolin, Sylvie Sebillaud, Benoît Rieger, Aurélie Thomas, Marie-Josèphe Décret, Manuella Burgart, Laurent Gaté, Benoît Cossec, Pierre Campo
Methylethylketone (MEK) is widely used in industry, often in combination with other compounds. Although nontoxic, it can make other chemicals harmful. This study investigates the fate of MEK in rat blood, brain and urine as well as its hepatic metabolism following inhalation over 1 month (at 20, 200 or 1400 ppm). MEK did not significantly accumulate in the organism: blood concentrations were similar after six-hour or 1-month inhalation periods, and brain concentrations only increased slightly after 1 month's exposure...
February 28, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#16
Dan Cheng, Wang Xu, Lin Yuan, Xiaobing Zhang
Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction-based fluorescent probes (Naph-ONOO(-) and Rhod-ONOO(-)) for ONOO(-) through a novel and universally applicable mechanism: ONOO(-)-mediated deprotection of α-keto caged fluorophores. Among them, Rhod-ONOO(-) can selectively accumulate and react in mitochondria, one of the main sources of ONOO(-), with a substantial lower nanomolar sensitivity of 43 nM...
July 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28626488/hepatotoxicity-in-rats-induced-by-aqueous-extract-of-polygoni-multiflori-radix-root-of-polygonum-multiflorum-related-to-the-activity-inhibition-of-cyp1a2-or-cyp2e1
#17
Deng-Ke Li, Jing Chen, Zhen-Zhen Ge, Zhen-Xiao Sun
The objective of this study is to investigate the relationship between the hepatotoxicity induced by Polygoni Multiflori Radix (PMR, root of Polygonum multiflorum Thunb., He Shou Wu) and the activity of CYP1A2 or CYP2E1 in the rat liver. Levels of rat serum transaminases ALT and AST were not altered but the activity of CYP1A2 or CYP2E1 in the rat liver was significantly inhibited after oral administration of aqueous extract of PMR under the experimental dosage. However, levels of ALT and AST were significantly increased and the activity of CYP1A2 or CYP2E1 was significantly decreased after injection of specific inhibitor for CYP1A2 or CYP2E1 combined with oral administration of aqueous extract of PMR, especially under the repeated treatment over interval times...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28614988/in-vitro-inhibitory-effects-of-dihydromyricetin-on-human-liver-cytochrome-p450-enzymes
#18
Lu Liu, Sen Sun, Hongbing Rui, Xiaohua Li
CONTEXT: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. MATERIALS AND METHODS: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28612092/involvement-of-cytochrome-p450-in-cisplatin-treatment-implications-for-toxicity
#19
REVIEW
Júlia Coelho França Quintanilha, Vanessa Marcilio de Sousa, Marília Berlofa Visacri, Laís Sampaio Amaral, Roseane Maria Maia Santos, Tomás Zambrano, Luis Antonio Salazar, Patricia Moriel
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28606510/in-vitro-inhibitory-mechanisms-and-molecular-docking-of-1-s-1-acetoxychavicol-acetate-on-human-cytochrome-p450-enzymes
#20
A K M Mahmudul Haque, Kok Hoong Leong, Yoke Lin Lo, Khalijah Awang, Noor Hasima Nagoor
BACKGROUND: The compound, 1'-S-1'-acetoxychavicol acetate (ACA), isolated from the rhizomes of a Malaysian ethno-medicinal plant, Alpinia conchigera Griff. (Zingiberaceae), was previously shown to have potential in vivo antitumour activities. In the development of a new drug entity, potential interactions of the compound with the cytochrome P450 superfamily metabolizing enzymes need to be ascertain. PURPOSE: The concomitant use of therapeutic drugs may cause potential drug-drug interactions by decreasing or increasing plasma levels of the administered drugs, leading to a suboptimal clinical efficacy or a higher risk of toxicity...
July 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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