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Hepatotoxicity

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https://www.readbyqxmd.com/read/28636348/the-development-of-an-aryloxazole-class-of-hepatitis-c-virus-inhibitors-targeting-the-entry-stage-of-the-viral-replication-cycle
#1
Shanshan He, Kelin Li, Billy Lin, Zonyi Hu, Jingbo Xiao, Xin Hu, Amy Q Wang, Xin Xu, Marc Ferrer, Noel Southall, Wei Zheng, Jeffrey Aubé, Frank J Schoenen, Juan J Marugan, T Jake Liang, Kevin J Frankowski
Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps, such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#2
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28631137/assessment-of-titanium-dioxide-nanoparticles-tio2-nps-induced-hepatotoxicity-and-ameliorative-effects-of-cinnamomum-cassia-in-sprague-dawley-rats
#3
Muhammad Shakeel, Farhat Jabeen, Rehana Iqbal, Abdul Shakoor Chaudhry, Sadia Zafar, Muhammad Ali, Muhammad Saleem Khan, Adeel Khalid, Samina Shabbir, Muhammad Saleem Asghar
This study assessed the protective effects of Cinnamomum cassia (cinnamon) bark extract in rats exposed to titanium dioxide nanoparticles or titanium dioxide bulk salt. For in vivo evaluation of the ameliorative role of the cinnamon extract, the experimental groups were orally administered with the cinnamon extract at different dose levels (50 or 100 or 150 mg/kg bodyweight) along with the subcutaneous injections of 150 mg/kg bodyweight titanium dioxide nanoparticles or titanium dioxide bulk salt. The extract showed significant ameliorative role on the antioxidant system in response to elevated levels of titanium dioxide nanoparticles or titanium dioxide bulk salt-induced oxidative stress...
June 19, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28630394/moringa-oleifera-based-diet-protects-against-nickel-induced-hepatotoxicity-in-rats
#4
Stephen Adeyemi Oluyomi, Sokolayemji Aroge Cincin, Adewumi Akanji Musbau
Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet or M. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment...
June 20, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28629535/enhanced-absorption-and-inhibited-metabolism-of-emodin-by-2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucopyranoside-possible-mechanisms-for-polygoni-multiflori-radix-induced-liver-injury
#5
Qiong Yu, Li-Long Jiang, Na Luo, Ya-Xi Fan, Jiang Ma, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) on the cellular absorption and human liver microsome metabolism of emodin...
June 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28628040/lipogenic-transcription-factor-chrebp-mediates-fructose-induced-metabolic-adaptations-to-prevent-hepatotoxicity
#6
Deqiang Q Zhang, Xin Tong, Kyle VanDommelen, Neil Gupta, Kenneth Stamper, Graham F Brady, Zhuoxian Meng, Jiandie D Lin, Liangyou Y Rui, M Bishr Omary, Lei Yin
Epidemiologic and animal studies implicate overconsumption of fructose in the development of nonalcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remain largely unknown. Here, we have presented evidence supporting the essential function of the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) in mediating adaptive responses to fructose and protecting against fructose-induced hepatotoxicity. In WT mice, a high-fructose diet (HFrD) activated hepatic lipogenesis in a ChREBP-dependent manner; however, in Chrebp-KO mice, a HFrD induced steatohepatitis...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#7
Dan Cheng, Wang Xu, Lin Yuan, Xiao-Bing 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 -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 nano-molar sensitivity of 43 nM...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28627253/protective-effects-of-quercetin-on-nicotine-induced-oxidative-stress-in-hepg2-cells
#8
Amir Yarahmadi, Fatemeh Zal, Ayeh Bolouki
Nicotine is a natural component of tobacco plants and is responsible for the addictive properties of tobacco. Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS). The purpose of this work was to estimate the hepatotoxicity effect of nicotine on viability and on antioxidant defense system in cultures of HepG2 cell line and the other hand, ameliorative effect of querctin (Q) as an antioxidant was analyzed. Nicotine induced concentration dependent loss in HepG2 cell line viability...
June 19, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28626497/hepatoprotective-effect-of-polyphenol-enriched-fraction-from-folium-microcos-on-oxidative-stress-and-apoptosis-in-acetaminophen-induced-liver-injury-in-mice
#9
Hongtan Wu, Gang Zhang, Lisen Huang, Haiyue Pang, Na Zhang, Yupei Chen, Gueyhorng Wang
Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α-glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol-enriched fraction (FMF) from Folium Microcos. FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1-6 cells from hydrogen peroxide- (H2O2-) induced ROS production and apoptosis in vitro...
2017: Oxidative Medicine and Cellular Longevity
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
#10
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/28624886/pharmacokinetic-modelling-of-modified-acetylcysteine-infusion-regimens-used-in-the-treatment-of-paracetamol-poisoning
#11
Anselm Wong, Cornelia Landersdorfer, Andis Graudins
PURPOSE: Paracetamol overdose is common and is treated with acetylcysteine to prevent the development of hepatotoxicity. N-acetyl-p-benzoquinone imine (NAPQI) is the toxic metabolite of paracetamol overdose. We aimed to assess the expected acetylcysteine concentration time profiles following delivery of modified acetylcysteine regimens proposed for those at high and low risk of hepatotoxicity. In addition, we will determine acetylcysteine concentrations post-cessation of abbreviated infusions...
June 17, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28624627/histopathological-and-proteomic-responses-in-male-chinese-rare-minnow-gobiocypris-rarus-indicate-hepatotoxicity-following-benzotriazole-exposure
#12
Xuefang Liang, Jinmiao Zha, Christopher J Martyniuk, Zijian Wang, Ji Zhao
Benzotriazole (BT) and its associated derivatives are used ubiquitously in industrial processes, and can be detected in indoor temperature coolants and in chemicals designed to inhibit corrosion. This chemical has been widely detected in aquatic environments and shows some degree of environmental persistence. Evidence has shown that BT exposure can negatively affect endocrine systems and can result in neurotoxicity in fish. However, no study has examined whether this chemical exhibits hepatotoxicity in fish, and if so, what are the underlying mechanism associated with the damage...
June 15, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28624597/suppressive-effect-of-kamebakaurin-on-acetaminophen-induced-hepatotoxicity-by-inhibiting-lipid-peroxidation-and-inflammatory-response-in-mice
#13
Hiroki Yoshioka, Yutaka Aoyagi, Nobuyuki Fukuishi, Ming-Yu Gui, Yong-Ri Jin, Xu-Wen Li, Yoshiyuki Adachi, Naohito Ohno, Koichi Takeya, Yukio Hitotsuyanagi, Nobuhiko Miura, Tsunemasa Nonogaki
BACKGROUND: Kamebakaurin (KA) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. In the current study, we investigated whether pretreatment with KA could ameliorate acetaminophen (APAP)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice. METHODS: Seven-week-old C57BL/6J mice were orally administered KA or olive oil emulsion for seven days. Twenty-four hours after the last KA or olive oil administration, the mice were intraperitoneally injected with 400mg/kg APAP or saline under feed deprived condition...
April 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28623112/protective-and-prophylactic-effects-of-chlorogenic-acid-on-aluminum-induced-acute-hepatotoxicity-and-hematotoxicity-in-mice
#14
Dai Cheng, Xinyu Zhang, Lihan Xu, Xiang Li, Lihua Hou, Chunling Wang
The possible health impact of the exposures to Al from environment would be inevitable for humans. Using chelating agents and natural antioxidants against Al-induced biotoxicity become a natural and modern way to prevent the adverse effects of Al in people. This study was undertaken to determine the effectiveness of chlorogenic acid (CGA, 5-O-caffeoylquinic acid) in preventing aluminum chloride (AlCl3) induced hepatotoxicity and hematotoxicity in mice. Control, Al-treated (a single injection of 25 mg Al(3+)/kg, i...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28621747/novel-tacrine-scutellarin-hybrids-as-multipotent-anti-alzheimer-s-agents-design-synthesis-and-biological-evaluation
#15
Katarina Spilovska, Jan Korabecny, Vendula Sepsova, Daniel Jun, Martina Hrabinova, Petr Jost, Lubica Muckova, Ondrej Soukup, Jana Janockova, Tomas Kucera, Rafael Dolezal, Eva Mezeiova, Daniel Kaping, Kamil Kuca
A novel series of 6-chlorotacrine-scutellarin hybrids was designed, synthesized and the biological activity as potential anti-Alzheimer's agents was assessed. Their inhibitory activity towards human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), antioxidant activity, ability to cross the blood-brain barrier (BBB) and hepatotoxic profile were evaluated in vitro. Among these compounds, hybrid K1383, bearing two methylene tether between two basic scaffolds, was found to be very potent hAChE inhibitor (IC50 = 1...
June 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28621023/pediatric-liver-transplantation-for-fulminant-hepatic-failure-secondary-to-intentional-iron-overdose
#16
Joanne Lai, Jaime Chu, Ronen Arnon
Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation.
June 15, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28620673/first-evidence-of-pyrrolizidine-alkaloid-n-oxide-induced-hepatic-sinusoidal-obstruction-syndrome-in-humans
#17
Mengbi Yang, Jianqing Ruan, Hong Gao, Na Li, Jiang Ma, Junyi Xue, Yang Ye, Peter Pi-Cheng Fu, Jiyao Wang, Ge Lin
Pyrrolizidine alkaloids (PAs) are among the most potent phytotoxins widely distributed in plant species around the world. PA is one of the major causes responsible for the development of hepatic sinusoidal obstruction syndrome (HSOS) and exerts hepatotoxicity via metabolic activation to form the reactive metabolites, which bind with cellular proteins to generate pyrrole-protein adducts, leading to hepatotoxicity. PA N-oxides coexist with their corresponding PAs in plants with varied quantities, sometimes even higher than that of PAs, but the toxicity of PA N-oxides remains unclear...
June 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#18
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28619287/the-impact-of-black-seed-oil-on-tramadol-induced-hepatotoxicity-immunohistochemical-and-ultrastructural-study
#19
Nesreen Moustafa Omar, Mohammed Amin Mohammed
The natural herb, black seed (Nigella Sativa; NS) is one of the most important elements of folk medicine. The aim was to evaluate the impact of Nigella Sativa Oil (NSO) on the changes induced by tramadol in rat liver. Twenty four albino rats were used. CONTROL GROUP: given intraperitoneal and oral saline for 30days. TR-group: given intraperitoneal tramadol (20, 40, 80mg/kg/day) in the first, middle and last 10days of the experiment, respectively. TR+NS group: administered intraperitoneal tramadol in similar doses to TR-group plus oral NSO (4ml/kg/day) for 30days...
June 12, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28618413/induction-of-apoptosis-in-heparg-cell-line-by-aloe-emodin-through-generation-of-reactive-oxygen-species-and-the-mitochondrial-pathway
#20
Xiaoxv Dong, Jing Fu, Xingbin Yin, Changhai Qu, Chunjing Yang, Huyiligeqi He, Jian Ni
BACKGROUND/AIMS: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. METHODS: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining...
June 15, 2017: Cellular Physiology and Biochemistry
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