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https://www.readbyqxmd.com/read/28430162/ameliorative-effects-and-possible-molecular-mechanism-of-action-of-black-ginseng-panax-ginseng-on-acetaminophen-mediated-liver-injury
#1
Jun-Nan Hu, Zhi Liu, Zi Wang, Xin-Dian Li, Lian-Xue Zhang, Wei Li, Ying-Ping Wang
Background: Frequent overdosing of acetaminophen (APAP) has become the major cause of acute liver injury (ALI). The present study aimed to evaluate the potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice liver injuries and the underlying mechanisms of action were further investigated for the first time. Methods: Mice were treated with BG (300, 600 mg/kg) by oral gavage once a day for seven days. On the 7th day, all mice were treated with 250 mg/kg APAP which caused severe liver injury after 24 h and hepatotoxicity was assessed...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28425245/xenobiotic-drug-metabolizing-enzyme-and-tp53-polymorphisms-and-clinical-outcome-in-advanced-nonsmall-cell-lung-cancer-patients
#2
Volkan Karacaoğlan, Ahmet Oğuz Ada, Serdar Bilgen, Guzide Tuğba Çetinkaya, Emre Soydaş, Celalettin Semih Kunak, Sibel Meryem Alpar, Meral Gülhan, Mümtaz Işcan
BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP)...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28420359/saikosaponins-induced-hepatotoxicity-in-mice-via-lipid-metabolism-dysregulation-and-oxidative-stress-a-proteomic-study
#3
Xiaoyu Li, Xiaojiaoyang Li, Junxian Lu, Youyi Huang, Lili Lv, Yongfu Luan, Runping Liu, Rong Sun
BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28419832/dihydromyricetin-modulates-p62-and-autophagy-crosstalk-with-the-keap-1-nrf2-pathway-to-alleviate-ethanol-induced-hepatic-injury
#4
Ping Qiu, Yu Dong, Bo Li, Xian-Jie Kang, Chao Gu, Tao Zhu, Yun-Yun Luo, Min-Xia Pang, Wei-Feng Du, Wei-Hong Ge
Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure...
April 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28416145/the-ginkgo-biloba-extract-gbe-protects-the-kidney-from-damage-produced-by-a-single-and-low-dose-of-carbon-tetrachloride-in-adult-male-rats
#5
R M Chávez-Morales, F Jaramillo-Juárez, M L Rodríguez-Vázquez, M C Martínez-Saldaña, F A Posadas Del Río, J A Garfias-López
Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl4...
April 13, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28414290/-the-effect-of-isatin-on-protein-protein-interactions-between-cytochrome-b5-and-cytochromes-p450
#6
P V Ershov, E O Yablokov, Yu V Mezentsev, L A Kalushskiy, A V Florinskaya, A V Veselovsky, O V Gnedenko, A A Gilep, S A Usanov, A E Medvedev, A S Ivanov
Cytochromes P450 (CYP) are involved in numerous biochemical processes including metabolism of xenobiotics, biosynthesis of cholesterol, steroid hormones etc. Since some CYP catalyze indol oxidation to isatin, we have hypothesized that isatin can regulate protein-protein interactions (PPI) between components of the CYP system thus representing a (negative?) feedback mechanism. The aim of this study was to investigate a possible effect of isatin on interaction of human CYP with cytochrome b5 (CYB5A). Using the optical biosensor test system employing surface plasmon resonance (SPR) we have investigated interaction of immobilized CYB5A with various CYP in the absence and in the presence of isatin...
March 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28409533/control-of-oxygen-tension-recapitulates-zone-specific-functions-in-human-liver-microphysiology-systems
#7
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28396637/membrane-associated-progesterone-receptors-promiscuous-proteins-with-pleiotropic-functions-focus-on-interactions-with-cytochromes-p450
#8
REVIEW
Chang S Ryu, Kathrin Klein, Ulrich M Zanger
Membrane-associated progesterone receptors (MAPR) are a group of four rather small, partially homologous proteins, which share a similar non-covalent heme-binding domain that is related to cytochrome b5, a well-known functional interaction partner of microsomal cytochrome P450 (CYP) monooxygenase systems. Apart from their structural similarities the four proteins progesterone membrane component 1 (PGRMC1, also referred to as IZA, sigma-2 receptor, Dap1), PGRMC2, neudesin (NENF) and neuferricin (CYB5D2) display surprisingly divergent and multifunctional physiological properties related to cholesterol/steroid biosynthesis, drug metabolism and response, iron homeostasis, heme trafficking, energy metabolism, autophagy, apoptosis, cell cycle regulation, cell migration, neural functions, and tumorigenesis and cancer progression...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#9
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28387740/protective-effect-of-bicyclol-on-anti-tuberculosis-drug-induced-liver-injury-in-rats
#10
Xin Liu, Manman Zhao, Jiaqi Mi, Hui Chen, Li Sheng, Yan Li
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods...
April 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28385522/transcriptome-analysis-of-the-effects-of-chitosan-on-the-hyperlipidemia-and-oxidative-stress-in-high-fat-diet-fed-mice
#11
Bin Wang, Sicong Zhang, Xiaoya Wang, Shuo Yang, Qixing Jiang, Yanshun Xu, Wenshui Xia
Transcriptome analysis was performed to investigate the alterations in gene expression after chitosan (CS) treatment on the liver of mice fed with high-fat diet (HFD). The results showed that the body weight, the liver weight and the epididymal fat mass of HFD mice, which were 62.98%, 46.51% and 239.37%, respectively, higher than those of control mice, could be significantly decreased by chitosan supplementation. Also, high-fat diet increased both plasma lipid and liver lipid as compared with the control mice...
April 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28385499/the-induction-of-cytochrome-p450-2e1-by-ethanol-leads-to-the-loss-of-synaptic-proteins-via-ppar%C3%AE-down-regulation
#12
Shufang Na, Jie Li, Huibo Zhang, Yueran Li, Zheqiong Yang, Yanjun Zhong, Guicheng Dong, Jing Yang, Jiang Yue
Ethanol, one of the most commonly abused substances throughout history, is a substrate and potent inducer of cytochrome P450 2E1 (CYP2E1). Our previous study showed that brain CYP2E1 was induced by chronic ethanol treatment and was associated with ethanol-induced neurotoxicity in rats. We therefore investigated the possible mechanism of brain CYP2E1 involvement in ethanol-induced neurodegeneration. Compared with the controls, chronic ethanol treatment (3.0g/kg, i.g., 160 days) significantly increased CYP2E1 mRNA levels in the rat cortex, but the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and the pre- and post-synaptic proteins (synaptophysin, SYP, and drebrin1, DBN1) were decreased...
April 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28380415/anti-steatotic-and-anti-inflammatory-effects-of-hovenia-dulcis-thunb-extracts-in-chronic-alcohol-fed-rats
#13
Ra-Yeong Choi, Moon-Jae Woo, Ju Ri Ham, Mi-Kyung Lee
The anti-steatotic and anti-inflammatory effects of fruit water extract (FW) and seed ethanol extract (SE) of Hovenia dulcis Thunb. in chronic alcohol-fed rats were investigated. Rats were fed a liquid diet containing 36% calories from alcohol and orally administered FW or SE (300 and 500mg/kg/day). Both FW and SE reduced hepatic lipid contents and droplets, serum lipid concentration and inflammatory markers (hs-CRP, TNF-α and IL-6) levels compared with the alcohol control group. Alcohol led to significant decreases in the hepatic fatty acid oxidative gene (Ppargc1a, Cpt1a and Acsl1) levels, while it significantly increased the Myd88 and Tnfa gene levels...
April 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28379345/epididymal-cyp2e1-plays-a-critical-role-in-acrylamide-induced-dna-damage-in-spermatozoa-and-paternally-mediated-embryonic-resorptions
#14
A L Katen, P Sipila, L A Mitchell, S J Stanger, B Nixon, S D Roman
Acrylamide is a ubiquitous toxicant in human lives, due to its formation in many food products. Acrylamide induces dominant lethal mutations with administration of 25 mg/kg bw/day for 5 days in male mice. Cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) is responsible for this dominant lethality. CYP2E1 is the only enzyme responsible for the conversion of acrylamide to the highly reactive metabolite glycidamide, which forms adduct with DNA. CYP2E1 is present predominantly in the liver, as well as the brain, kidney, intestines and spleen...
March 31, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28376352/metabolic-profiling-of-five-flavonoids-from-dragon-s-blood-in-human-liver-microsomes-using-high-performance-liquid-chromatography-coupled-with-high-resolution-mass-spectrometry
#15
Yujuan Li, Yushi Zhang, Rui Wang, Lizhong Wei, Yulin Deng, Wei Ren
Although much is known about the pharmacological activities of Dragon's Blood (DB, a traditional Chinese herb), its metabolism in human liver microsomes (HLMs) and the cytochrome P450 (CYP) enzymes has not been studied. This study aims to identify the metabolic profile of five flavonoids (loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone) from DB in HLMs as well as the CYP enzymes that are involved in the metabolism of them. High-resolution mass spectrometry was used to characterize the structures of their metabolites and 10 cDNA-expressed CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) were used to verify which isozymes mediate in the metabolism of the metabolites...
March 27, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28360860/acanthoic-acid-can-partially-prevent-alcohol-exposure-induced-liver-lipid-deposition-and-inflammation
#16
You-Li Yao, Xin Han, Zhi-Man Li, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu
Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28360859/dexamethasone-pretreatment-alleviates-isoniazid-lipopolysaccharide-hepatotoxicity-inhibition-of-inflammatory-and-oxidative-stress
#17
Hozeifa M Hassan, Hongli Guo, Bashir A Yousef, Ding Ping-Ping, Luyong Zhang, Zhenzhou Jiang
Isoniazid (INH) remains a cornerstone key constitute of the current tuberculosis management strategy, but its hepatotoxic potentiality remains a significant clinical problem. Our previous findings succeed to establish a rat model of INH hepatotoxicity employing the inflammatory stress theory in which non-injurious doses of inflammatory-mediating agent bacterial lipopolysaccharides (LPS) augmented the toxicity of INH that assist to uncover the mechanisms behind INH hepatotoxicity. Following LPS exposure, several inflammatory cells are activated and it is likely that the consequences of this activation rather than direct hepatocellular effects of LPS underlie the ability of LPS to augment toxic responses...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28357584/association-of-cytochrome-p4502e1-and-nad-p-h-quinone-oxidoreductase-1-genetic-polymorphisms-with-susceptibility-to-large-artery-atherosclerotic-ischemic-stroke-a-case-control-study-in-the-turkish-population
#18
Aysun Türkanoğlu Özçelik, Birsen Can Demirdöğen, Şeref Demirkaya, Orhan Adalı
Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP...
March 29, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28344482/the-genetic-profiles-of-cyp1a1-cyp1a2-and-cyp2e1-enzymes-as-susceptibility-factor-in-xenobiotic-toxicity-in-turkish-population
#19
Merve Arici, Gül Özhan
Evaluation and sequencing of heritable alterations in the human genome and the large-scale identification of gene polymorphism for understanding the genetic background of individuals in response to potential toxicants are provided by toxicogenetics. Cytochrome P450 (CYP) enzymes play role not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds. CYP1A1, CYP1A2 and CYP2E1 enzymes, which are in phase I enzymes, are responsible for metabolic activation and detoxification of several chemical compounds...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28341391/mice-lacking-liver-specific-%C3%AE-catenin-develop-steatohepatitis-and-fibrosis-after-iron-overload
#20
Morgan E Preziosi, Sucha Singh, Erika V Valore, Chun-Ling Jung, Branimir Popovic, Minakshi Poddar, Shanmugam Nagarajan, Tomas Ganz, Satdarshan P Monga
BACKGROUND & AIMS: Iron overload disorders such as hereditary hemochromatosis and iron-loading anemias are a common cause of morbidity from liver diseases and increase risk of hepatic fibrosis and hepatocellular carcinoma (HCC). Once iron-induced damage occurs, treatment options are limited partly because of the lack of animal models recapitulating human disease, which do not exhibit relevant sequelae after chronic iron overload. METHODS: Since liver-specific β-catenin knockout mice (KO) are susceptible to injury, fibrosis and tumorigenesis following chemical carcinogen exposure, iron-overload diet was administered to KO and littermate control (CON) mice for various times...
March 21, 2017: Journal of Hepatology
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