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Drug induced hepatitis

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https://www.readbyqxmd.com/read/29141109/hepatic-ppar%C3%AE-mediates-the-major-metabolic-effects-of-wy-14643
#1
Guolin Li, Chad N Brocker, Cen Xie, Tingting Yan, Audrey Noguchi, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez
BACKGROUND AND AIM: Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue-specific functions of PPARα remain to be elucidated. This study aimed to explore the tissue-specific functions of PPARα in response to Wy-14643. METHODS: A hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with the potent PPARα agonist Wy-14643...
November 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29140706/a-galactosylated-pro-drug-of-ursodeoxycholic-acid-design-synthesis-characterization-and-pharmacological-effects-in-a-rat-model-of-estrogen-induced-cholestasis
#2
Francesca Di Guida, Claudio Pirozzi, Salvatore Magliocca, Anna Santoro, Adriano Lama, Roberto Russo, Maria Nieddu, Lucia Burrai, Gianpiero Boatto, Maria Pina Mollica, Federica Sodano, Loretta Lazzarato, Konstantin Chegaev, Rosaria Meli, Giuseppina Mattace Raso, Maria Grazia Rimoli
Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29137114/natural-cyclopeptide-ra-xii-a-new-autophagy-inhibitor-suppresses-protective-autophagy-for-enhancing-apoptosis-through-ampk-mtor-p70s6k-pathways-in-hepg2-cells
#3
Lihua Song, Zhe Wang, Yurong Wang, Di Guo, Jianhong Yang, Lijuan Chen, Ninghua Tan
Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136753/-metabolomics-study-of-tris-2-chloroethyl-phosphate-induced-hepaotoxicity-and-nephrotoxicity-in-sprague-dawley-rats
#4
W Q Yang, F Zhao, L Li, Y J Fang
Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50±2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg·kg(-1)·d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29133031/chloroquine-upregulates-trail-trailr2-expression-and-potentiates-doxorubicin-anti-tumor-activity-in-thioacetamide-induced-hepatocellular-carcinoma-model
#5
Sahar A Helmy, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El Gayar
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29132235/a-cell-based-assay-to-investigate-hypolipidemic-effects-of-nonalcoholic-fatty-liver-disease-therapeutics
#6
Tapan Dave, Arno William Tilles, Muralikrishna Vemula
In the recent past, there has been a growing interest in developing nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) therapeutics. As a result, a need for in vitro cell models of human hepatic steatosis and high-throughput assays to measure intracellular lipid levels has arisen. To address this growing need, we optimized the conditions based on the current literature to fatten HepG2 hepatocytes by adding a mixture of saturated and unsaturated fatty acids (oleate/palmitate, 2:1 molar ratio) without inducing any overt cytotoxicity...
November 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29129847/effects-of-ketoconazole-on-cyclophosphamide-metabolism-evaluation-of-cyp3a4-inhibition-effect-using-the-in-vitro-and-in-vivo-models
#7
Le Yang, Chenyang Yan, Feng Zhang, Bo Jiang, Shouhong Gao, Youtian Liang, Lifeng Huang, Wansheng Chen
Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP...
November 13, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29129047/hepaprotective-effect-of-standardized-ecklonia-stolonifera-formulation-on-ccl%C3%A2-induced-liver-injury-in-sprague-dawley-rats
#8
Jae-Hyuk Byun, Jun Kim, Se-Young Choung
The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl₄)-induced liver injury in Sprague Dawley rat...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29127992/leishmania-infantum-exerts-immunomodulation-in-canine-kupffer-cells-reverted-by-meglumine-antimoniate
#9
A Rodrigues, D Santos-Mateus, G Alexandre-Pires, A Valério-Bolas, M Rafael-Fernandes, M A Pereira, D Ligeiro, J de Jesus, R Alves-Azevedo, S Lopes-Ventura, M Santos, A M Tomás, I Pereira da Fonseca, G Santos-Gomes
Kupffer cells (KC) are the liver macrophage population that resides in the hepatic sinusoids and efficiently phagocyte pathogens by establishing an intimate contact with circulating blood. KC constitute the liver host cells in Leishmania infection, nevertheless little is described about their role, apart from their notable contribution in granulomatous inflammation. The present study aims to investigate how canine KC sense and react to the presence of Leishmania infantum promastigotes and amastigotes by evaluating the gene expression of specific innate immune cell receptors and cytokines, as well as the induction of nitric oxide and urea production...
December 2017: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/29123032/pregnane-x-receptor-promotes-ethanol-induced-hepatosteatosis-in-mice
#10
Sora Choi, Prince Neequaye, Samuel W French, Frank J Gonzalez, Maxwell A Gyamfi
The pregnane X receptor (PXR, NR1I2) is a xenobiotic-sensing nuclear receptor that modulates the metabolic response to drugs and toxic agents. Both PXR activation and deficiency promote hepatic triglyceride accumulation, a hallmark feature of alcoholic liver disease (ALD). However, the molecular mechanism of PXR-mediated activation of ethanol (EtOH)-induced steatosis is unclear. Here, using male wild type (WT) and Pxr-null mice we examined PXR-mediated regulation of chronic EtOH-induced hepatic lipid accumulation and hepatotoxicity...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29120909/rivaroxaban-induced-hepatotoxicity-review-of-the-literature-and-report-of-new-cases
#11
Anna Licata, Fania Puccia, Vania Lombardo, Antonietta Serruto, Maria G Minissale, Ilaria Morreale, Lydia Giannitrapani, Maurizio Soresi, Giuseppe Montalto, Piero L Almasio
AIM/OBJECTIVE/BACKGROUND: Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2008-2016 was carried out...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29118984/clinical-trial-protocol-for-tardox-a-phase-i-study-to-investigate-the-feasibility-of-targeted-release-of-lyso-thermosensitive-liposomal-doxorubicin-thermodox%C3%A2-using-focused-ultrasound-in-patients-with-liver-tumours
#12
Paul C Lyon, Lucy F Griffiths, Jenni Lee, Daniel Chung, Robert Carlisle, Feng Wu, Mark R Middleton, Fergus V Gleeson, Constantin C Coussios
Background: TARDOX is a Phase I single center study of ultrasound triggered targeted drug delivery in adult oncology patients with incurable liver tumours. This proof of concept study is designed to demonstrate the safety and feasibility of targeted drug release and enhanced delivery of doxorubicin from thermally sensitive liposomes (ThermoDox®) triggered by mild hyperthermia induced by focused ultrasound in liver tumours. A key feature of the study is the direct quantification of the doxorubicin concentration before and after ultrasound exposure from tumour biopsies, using high performance liquid chromatography (HPLC)...
2017: Journal of Therapeutic Ultrasound
https://www.readbyqxmd.com/read/29116160/ilex-latifolia-thunb-protects-mice-from-hfd-induced-body-weight-gain
#13
Hailan Wu, Yue-Lei Chen, Yueyuan Yu, Jin Zang, Yikuan Wu, Zhao He
Kuding tea is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Ilex latifolia Thunb (kuding tea), one of the large leaf kuding tea species, in the prevention of the development of obesity remains to be determined. We show here that 7-week-old male mice treated with an Ilex latifolia Thunb supplement for 14 weeks were resistant to HFD-induced body weight gain and hepatic steatosis, accompanied by improved insulin sensitivity. Ilex latifolia Thunb supplementation dramatically reduced the systemic and tissue inflammation levels of mice via reducing pro-inflammatory cytokine levels, increasing anti-inflammatory cytokine levels in the circulation and inhibiting p38 MAPK and p65 NF-κB signaling in adipose tissue...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29112010/potential-visualization-of-sorafenib-induced-acidosis-using-11c-acetate-pet-ct-in-patients-with-hepatocellular-carcinoma
#14
Seong Young Kwon, Dong-Yeon Kim, Jung-Joon Min, Woo Kyun Bae
C-acetate uptake could be increased in physiologic or inflammatory conditions without evidence of cancer. We report a hepatocellular carcinoma patient with sorafenib-induced metabolic acidosis, who showed increased hepatic uptake of C-acetate. C-acetate PET/CT might be a potentially useful surrogate marker to monitor these adverse effects via the changes in C-acetate uptake patterns from before to after drug withdrawal.
November 3, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29108197/-advances-in-clinical-differentiation-between-immunological-and-drug-induced-liver-injury
#15
Y Wang, Y N Li, J Zhang, B M Wang, L Zhou
The differentiation between autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) is a difficult task in clinical practice. Some AIH patients had a medication history before disease onset, and some DILI patients may have positive serum antibody. In addition, these two groups of patients have similar clinical symptoms, serological examination results, and liver histopathology, which lead to the difficulties in differentiation. However, correct differential diagnosis is of great significance in making clinical treatment decisions and preventing liver cirrhosis...
September 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29108136/application-and-optimisation-of-the-comparison-on-extreme-laboratory-tests-cert-algorithm-for-detection-of-adverse-drug-reactions-transferability-across-national-boundaries
#16
Mun Yee Tham, Qing Ye, Pei San Ang, Liza Y Fan, Dukyong Yoon, Rae Woong Park, Zheng Jye Ling, James W Yip, Bee Choo Tai, Stephen Jw Evans, Cynthia Sung
PURPOSE: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system...
November 6, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29107284/superior-reductions-in-hepatic-steatosis-and-fibrosis-with-co-administration-of-a-glucagon-like-peptide-1-receptor-agonist-and-obeticholic-acid-in-mice
#17
Hani Jouihan, Sarah Will, Silvia Guionaud, Michelle L Boland, Stephanie Oldham, Peter Ravn, Anthony Celeste, James L Trevaskis
OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is an unmet need associated with metabolic syndrome. There are no approved therapies for NASH; however, glucagon-like peptide-1 receptor (GLP-1R) and farnesoid-X receptor (FXR) agonists are promising drug targets. We investigated the therapeutic effects of co-administration of a GLP-1R agonist, IP118, with FXR agonist obeticholic acid (OCA) in mice. METHODS: OCA and IP118 alone and in combination were sub-chronically administered to Lep(ob)/Lep(ob) mice with diet-induced NASH or diet-induced obese (DIO) mice...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#18
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#19
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29103340/immunogenicity-of-branched-polyethylene-glycol-modified-interferon-alpha
#20
Weidong Zhou, Daru Lu, Xiaojin Liao, Lu Zhuang, Li Sun
AIM: To assess the immunogenicity of Peginterferon alpha-2 b(Pegberon) and its effect on the efficacy and safety in phase III clinical trial, by comparing it with the control drug Pegasys. METHODS: 770 patients were recruited in total. 509 were treated with Pegberon plus ribavirin and 261 were treated with Pegasys plus ribavirin. After treatment of 12 and 24 weeks, plasma samples were collected from individual patients for detecting the anti-therapeutic antibodies (ATA) and hepatitis C RNA(HCV RNA), to evaluate the production of antibodies and their adverse effect on the efficacy and safety of the treatments...
November 6, 2017: Immunopharmacology and Immunotoxicology
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