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https://www.readbyqxmd.com/read/27823623/the-water-extract-of-veratrilla-baillonii-could-attenuate-the-subacute-toxicity-induced-by-aconitum-brachypodum
#1
You Yu, Xue-Jia Yi, Zhi-Yi Mei, Jun Li, Xian-Ju Huang, Guang-Zhong Yang, Li-Qun Ma, Yue Gao
BACKGROUND: Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27488982/effects-of-acute-exposure-to-sublethal-waterborne-cadmium-on-energy-homeostasis-in-silver-carp-hypophthalmichthys-molitrix
#2
Jie Pi, Xuelin Li, Ting Zhang, Deliang Li
Effects of acute exposure to sublethal waterborne cadmium (Cd) on energy homeostasis in filter-feeding fishes have rarely been studied. The response patterns of energy substances were investigated in juvenile silver carp (Hypophthalmichthys molitrix) exposed to sublethal waterborne Cd for 96 h. The results showed the 96hLC50 of Cd on juvenile silver carp was 1.723 mg/L. Sublethal acute exposure of Cd significantly affected the energy homeostasis of juvenile silver carp, including increase in plasma glucose and lactate, and decrease in plasma triglyceride, muscle glycogen and triglyceride and liver glycogen...
October 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27465948/-role-of-farnesoid-x-receptor-in-rats-with-acute-cholestatic-hepatitis
#3
Y Ding, X L Xiong, L Zhao, H R Li
OBJECTIVE: To investigate the role of farnesoid X receptor (FXR) and its downstream molecules small heterodimer partner (SHP), UDP-glucuronosyltransferase 2B4 (UGT2B4), and bile salt export pump (BSEP) in rats with acute cholestatic hepatitis. METHODS: A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group, with 10 rats in each group. The rats in the model group were given a single dose (50 mg/kg) ofα-naphthyl isothiocyanate by gavage to establish the animal model of acute cholestatic hepatitis...
June 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27452039/mechanisms-of-ccl4-induced-liver-fibrosis-with-combined-transcriptomic-and-proteomic-analysis
#4
Shu Dong, Qi-Long Chen, Ya-Nan Song, Yang Sun, Bin Wei, Xiao-Yan Li, Yi-Yang Hu, Ping Liu, Shi-Bing Su
The classic toxicity of carbon tetrachloride (CCl4) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl4-induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl4 in liver fibrosis. Wistar rats were treated with CCl4 for 9 weeks...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27156792/do-managed-alcohol-programs-change-patterns-of-alcohol-consumption-and-reduce-related-harm-a-pilot-study
#5
Kate Vallance, Tim Stockwell, Bernie Pauly, Clifton Chow, Erin Gray, Bonnie Krysowaty, Kathleen Perkin, Jinhui Zhao
BACKGROUND: Managed alcohol programs (MAPs) are a harm reduction strategy for people with severe alcohol dependence and unstable housing. MAPs provide controlled access to alcohol usually alongside accommodation, meals, and other supports. Patterns of alcohol consumption and related harms among MAP participants and controls from a homeless shelter in Thunder Bay, Ontario, were investigated in 2013. METHODS: Structured interviews were conducted with 18 MAP and 20 control participants assessed as alcohol dependent with most using non-beverage alcohol (NBA)...
2016: Harm Reduction Journal
https://www.readbyqxmd.com/read/27132127/esterase-detoxication-of-acetylcholinesterase-inhibitors-using-human-liver-samples-in-vitro
#6
Virginia C Moser, Stephanie Padilla
Organophosphorus (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxication can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON1) are considered factors underlying age-related sensitivity differences. We used an in vitro system to measure detoxication of AChE-inhibiting pesticides mediated via these esterases. Recombinant human AChE was used as a bioassay of inhibitor concentration following incubation with detoxifying tissue: liver plus Ca(+2) (to stimulate PON1s, measuring activity of both esterases) or EGTA (to inhibit PON1s, thereby measuring CaE activity)...
April 15, 2016: Toxicology
https://www.readbyqxmd.com/read/27071940/generation-of-a-new-model-rat-nrf2-knockout-rats-are-sensitive-to-aflatoxin-b1-toxicity
#7
Keiko Taguchi, Misaki Takaku, Patricia A Egner, Masanobu Morita, Takehito Kaneko, Tomoji Mashimo, Thomas W Kensler, Masayuki Yamamoto
THE TRANSCRIPTION FACTOR NRF2: (NF-E2-related-factor 2) REGULATES A BATTERY OF ANTIOXIDATIVE STRESS-RESPONSE GENES AND DETOXICATION GENES, AND NRF2 KNOCKOUT LINES OF MICE HAVE BEEN CONTRIBUTING CRITICALLY TO THE CLARIFICATION OF ROLES THAT NRF2 PLAYS FOR CELL PROTECTION HOWEVER, THERE ARE APPARENT LIMITATIONS IN USE OF THE MOUSE MODELS FOR INSTANCE, RATS EXHIBIT MORE SUITABLE FEATURES FOR TOXICOLOGICAL OR PHYSIOLOGICAL EXAMINATIONS THAN MICE IN THIS STUDY, WE GENERATED 2 LINES OF NRF2 KNOCKOUT RATS BY USING A GENOME EDITING TECHNOLOGY; 1 LINE HARBORS A 7-BP DELETION Δ7 AND THE OTHER LINE HARBORS A 1-BP INSERTION +1 IN THE NRF2 GENE IN THE LIVERS OF RATS HOMOZYGOUSLY DELETING THE NRF2 GENE, AN ACTIVATOR OF NRF2 SIGNALING, CDDO-IM, COULD NOT INDUCE EXPRESSION OF REPRESENTATIVE NRF2 TARGET GENES TO EXAMINE ALTERED TOXICOLOGICAL RESPONSE, WE TREATED THE NRF2 KNOCKOUT RATS WITH AFLATOXIN B1 AFB1, A CARCINOGENIC MYCOTOXIN THAT ELICITS GENE MUTATIONS THROUGH BINDING OF ITS METABOLITES TO DNA AND FOR WHICH THE RAT HAS BEEN PROPOSED AS A REASONABLE SURROGATE FOR HUMAN TOXICITY INDEED, IN THE NRF2 KNOCKOUT RAT LIVERS THE ENZYMES OF THE AFB1 DETOXICATION PATHWAY WERE SIGNIFICANTLY DOWNREGULATED SINGLE DOSE ADMINISTRATION OF AFB1 INCREASED HEPATOTOXICITY AND BINDING OF AFB1-N7-GUANINE TO HEPATIC DNA IN NRF2 KNOCKOUT RATS COMPARED WITH WILD-TYPE NRF2 KNOCKOUT RATS REPEATEDLY TREATED WITH AFB1 WERE PRONE TO LETHALITY AND CDDO-IM WAS NO LONGER PROTECTIVE THESE RESULTS DEMONSTRATE THAT NRF2 KNOCKOUT RATS ARE QUITE SENSITIVE TO AFB1 TOXICITIES AND THIS RAT GENOTYPE EMERGES AS A NEW MODEL ANIMAL IN TOXICOLOGY...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/26757129/the-effects-of-heavy-metal-ions-phthalates-and-ochratoxin-a-on-oxidation-of-carcinogenic-aristolochic-acid-i-causing-balkan-endemic-nephropathy
#8
Frantisek Barta, Katerina Levova, Petr Hodek, Heinz H Schmeiser, Volker M Arlt, Marie Stiborova
OBJECTIVES: Balkan endemic nephropathy (BEN) is a chronic progressive fibrosis associated with upper urothelial carcinoma (UUC). Aetiology of BEN is still not fully explained. Although carcinogenic aristolochic acid I (AAI) was proven as the major cause of BEN/UUC, this nephropathy is considered to be multifactorial. Hence, we investigated whether other factors considered as potential causes of BEN [a mycotoxin ochratoxin A (OTA), Cd, Pb, Se and As ions and organic compounds (i.e. phthalates) released from lignite deposits in BEN areas] can influence detoxication of AAI, whose concentrations are crucial for BEN development...
2015: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/26719282/antitoxic-effect-of-veratrilla-baillonii-on-the-acute-toxicity-in-mice-induced-by-aconitum-brachypodum-one-of-the-genus-aconitum
#9
Yue-Bin Ge, Yi Jiang, Huan Zhou, Mi Zheng, Jun Li, Xian-Ju Huang, Yue Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum brachypodum Diels (Family Ranunculaceae) is well known for both its good therapy and high toxicity in Yunnan and Sichuan provinces in China. Noticeably, Veratrilla baillonii Franch (Family Gentianaceae), an ethnodrug used by Naxi and Lisu nationalities in Yunnan Province, has been widely considered to possess antitoxic effects on Aconitum plants in herbal therapy and folklore medicines. MATERIALS AND METHODS: The present study was conducted to determine the detoxic activities of the water decoction of Veratrilla baillonii Franch (WVBF) on the the chloroform fraction of Aconitum brachypodum Diels (CFA) induced acute toxicity in mice...
February 17, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/26697674/progress-on-mechanism-of-tripterygium-wilfordii-induced-liver-injury-and-detoxification-mechanism-of-licorice
#10
Ling-juan Cao, Miao Yan, Huan-de Li, Bi-kui Zhang, Ping-fei Fang
Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems...
July 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/26583703/effect-of-cytochrome-p450-reductase-deficiency-on-2-amino-9h-pyrido-2-3-b-indole-metabolism-and-dna-adduct-formation-in-liver-and-extrahepatic-tissues-of-mice
#11
Robert J Turesky, Dmitri Konorev, Xiaoyu Fan, Yijin Tang, Lihua Yao, Xinxin Ding, Fang Xie, Yi Zhu, Qing-Yu Zhang
2-Amino-9H-pyrido[2,3-b]indole (AαC), a carcinogen formed during the combustion of tobacco and cooking of meat, undergoes cytochrome P450 (P450) metabolism to form the DNA adduct N-(deoxyguanosin-8-yl)-2-amino-9H-pyrido[2,3-b]indole (dG-C8-AαC). We evaluated the roles of P450 expressed in the liver and intestine to bioactivate AαC by employing male B6 wild-type (WT) mice, liver-specific P450 reductase (Cpr)-null (LCN) mice, and intestinal epithelium-specific Cpr-null (IECN) mice. Pharmacokinetic parameters were determined for AαC, 2-amino-9H-pyrido[2,3-b]indol-3-yl sulfate (AαC-3-OSO3H), and N(2)-(β-1-glucosidurony1)-2-amino-9H-pyrido[2,3-b]indole (AαC-N(2)-Glu) with animals dosed by gavage with AαC (13...
December 21, 2015: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/26523953/what-are-the-potential-sites-of-protein-arylation-by-n-acetyl-p-benzoquinone-imine-napqi
#12
Michael G Leeming, Luke F Gamon, Uta Wille, William A Donald, Richard A J O'Hair
Acetaminophen (paracetamol, APAP) is a safe and widely used analgesic medication when taken at therapeutic doses. However, APAP can cause potentially fatal hepatotoxicity when taken in overdose or in patients with metabolic irregularities. The production of the electrophilic and putatively toxic compound N-acetyl-p-benzoquinone imine (NAPQI), which cannot be efficiently detoxicated at high doses, is implicated in APAP toxicity. Numerous studies have identified that excess NAPQI can form covalent linkages to the thiol side chains of cysteine residues in proteins; however, the reactivity of NAPQI toward other amino acid side chains is largely unexplored...
November 16, 2015: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/26212543/metabolomics-reveals-the-formation-of-aldehydes-and-iminium-in-gefitinib-metabolism
#13
Xing Liu, Yuanfu Lu, Xinfu Guan, Bingning Dong, Hemantkumar Chavan, Jin Wang, Yiqing Zhang, Partha Krishnamurthy, Feng Li
Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is widely used for the treatment of cancers, particularly non-small cell lung cancer. However, its clinical use is limited by multiple adverse effects associated with GEF, such as liver and lung injuries, severe nausea, and diarrhea. Although, the exact mechanism of GEF adverse effects are still unknown, xenobiotic-induced bioactivation is thought to play a significant role in GEF induced toxicity. Using a metabolomic approach, we investigated the metabolic pathways of GEF in human and mouse liver microsomes...
September 1, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26160117/comparative-proteomic-characterization-of-4-human-liver-derived-single-cell-culture-models-reveals-significant-variation-in-the-capacity-for-drug-disposition-bioactivation-and-detoxication
#14
COMPARATIVE STUDY
Rowena L C Sison-Young, Dimitra Mitsa, Rosalind E Jenkins, David Mottram, Eliane Alexandre, Lysiane Richert, Hélène Aerts, Richard J Weaver, Robert P Jones, Esther Johann, Philip G Hewitt, Magnus Ingelman-Sundberg, Christopher E P Goldring, Neil R Kitteringham, B Kevin Park
In vitro preclinical models for the assessment of drug-induced liver injury (DILI) are usually based on cryopreserved primary human hepatocytes (cPHH) or human hepatic tumor-derived cell lines; however, it is unclear how well such cell models reflect the normal function of liver cells. The physiological, pharmacological, and toxicological phenotyping of available cell-based systems is necessary in order to decide the testing purpose for which they are fit. We have therefore undertaken a global proteomic analysis of 3 human-derived hepatic cell lines (HepG2, Upcyte, and HepaRG) in comparison with cPHH with a focus on drug metabolizing enzymes and transport proteins (DMETs), as well as Nrf2-regulated proteins...
October 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/26026145/nutritional-aspects-of-detoxification-in-clinical-practice
#15
REVIEW
John C Cline
Detoxification is a vital cellular task that, if lacking, can lead to early morbidity and mortality. The process of detoxification involves the mobilization, biotransformation, and elimination of toxicants of exogenous and endogenous origin. This article discusses the phase I and phase II detoxification and biotransformation pathways and promotes using food to support these highly complex processes. The author identifies the comprehensive elimination diet as a useful therapeutic tool for clinicians and patients to use to achieve detoxification...
May 2015: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/25860621/prediction-of-drug-induced-liver-injury-in-hepg2-cells-cultured-with-human-liver-microsomes
#16
Jong Min Choi, Soo Jin Oh, Ji-Yoon Lee, Jang Su Jeon, Chang Seon Ryu, Young-Mi Kim, Kiho Lee, Sang Kyum Kim
Drug-induced liver injury (DILI) via metabolic activation by drug-metabolizing enzymes, especially cytochrome P450 (CYP), is a major cause of drug failure and drug withdrawal. In this study, an in vitro model using HepG2 cells in combination with human liver microsomes was developed for the prediction of DILI. The cytotoxicity of cyclophosphamide, a model drug for bioactivation, was augmented in HepG2 cells cultured with microsomes in a manner dependent on exposure time, microsomal protein concentration, and NADPH...
May 18, 2015: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/25834030/targeted-screen-for-human-udp-glucuronosyltransferases-inhibitors-and-the-evaluation-of-potential-drug-drug-interactions-with-zafirlukast
#17
Shingo Oda, Ryoichi Fujiwara, Yuki Kutsuno, Tatsuki Fukami, Tomoo Itoh, Tsuyoshi Yokoi, Miki Nakajima
Inhibition of drug metabolizing enzymes is a major mechanism in drug-drug interactions (DDIs). A number of cases of DDIs via inhibition of UDP-glucuronosyltranseferases (UGTs) have been reported, although the changes in pharmacokinetics are relatively small in comparison with drugs that are metabolized by cytochrome P450s. Most of the past studies have investigated hepatic UGTs, although recent studies have revealed a significant contribution of UGTs in the small intestine to drug clearance. To evaluate potential DDIs caused by inhibition of intestinal UGTs, we assessed inhibitory effects of 578 compounds, including drugs, xenobiotics, and endobiotics, on human UGT1A8 and UGT1A10, which are major contributors to intestinal glucuronidation...
June 2015: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/25738501/intake-of-hydrolyzed-casein-is-associated-with-reduced-body-fat-accretion-and-enhanced-phase-ii-metabolism-in-obesity-prone-c57bl-6j-mice
#18
Morten Rahr Clausen, Xumin Zhang, Christian C Yde, Ditte B Ditlev, Haldis H Lillefosse, Lise Madsen, Karsten Kristiansen, Bjørn Liaset, Hanne C Bertram
The amount and form of dietary casein have been shown to affect energy metabolism and lipid accumulation in mice, but the underlying mechanisms are not fully understood. We investigated 48 hrs urinary metabolome, hepatic lipid composition and gene expression in male C57BL/6J mice fed Western diets with 16 or 32 energy% protein in the form of extensively hydrolyzed or intact casein. LC-MS based metabolomics revealed a very strong impact of casein form on the urinary metabolome. Evaluation of the discriminatory metabolites using tandem mass spectrometry indicated that intake of extensively hydrolyzed casein modulated Phase II metabolism associated with an elevated urinary excretion of glucuronic acid- and sulphate conjugated molecules, whereas glycine conjugated molecules were more abundant in urine from mice fed the intact casein diets...
2015: PloS One
https://www.readbyqxmd.com/read/25702432/-clinical-efficacy-of-reamberin-in-drug-addicts-with-hepatic-lesions
#19
V A Isakov, G S Arkhipov, V V Turkin, I V Aleksandrov
Infusion of 1.5% reamberin solution was shown to be a safe tool for combined therapy of severe viral hepatitis in drug addicts with signs of polyorganic lesions. Reamberin had detoxicating, antioxidative, hepato- and nephroprotective effects associated with clinical improvement, reduced hospital stay and normalized biochemical characteristics. Moreover, it increased the serum antioxidative potential and non-specific resistance of the patients.
2013: Klinicheskaia Meditsina
https://www.readbyqxmd.com/read/25633841/identification-of-glutathione-conjugates-of-acetylene-containing-positive-allosteric-modulators-of-metabotropic-glutamate-receptor-subtype-5
#20
Xiaoliang Zhuo, Xiaohua Stella Huang, Andrew P Degnan, Lawrence B Snyder, Fukang Yang, Hong Huang, Yue-Zhong Shu, Benjamin M Johnson
A recent medicinal chemistry campaign to identify positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) led to the discovery of potent compounds featuring an oxazolidinone structural core flanked by biaryl acetylene and haloaryl moieties. However, biotransformation studies of some of these mGluR5 PAMs demonstrated the formation of glutathione (GSH) conjugates. The conjugates in question were formed independently of NADPH as the main products in liver microsomes and liver cytosol (rat and human) and exhibited masses that were 307 u greater than their respective substrates, indicating the involvement of a reductive step in the formation of these metabolites...
April 2015: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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