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Drug induced hepatitis

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https://www.readbyqxmd.com/read/29331278/impact-of-treatment-with-a-protein-tyrosine-kinase-inhibitor-genistein-on-acute-and-chronic-experimental-schistosoma-mansoni-infection
#1
Maysa Mohamed Kamel Sobhy, Soheir Sayed Mahmoud, Shaimaa Helmy El-Sayed, Enas Mohamed Ali Rizk, Amira Raafat, Mohamed Sherif Ismail Negm
Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease...
January 10, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29330220/regulation-of-drug-metabolism-by-the-interplay-of-inflammatory-signaling-steatosis-and-xeno-sensing-receptors-in-heparg-cells
#2
Norman Tanner, Lisa Kubik, Claudia Luckert, Maria Thomas, Ute Hofmann, Ulrich M Zanger, Linda Bohmert, Alfonso Lampen, Albert Braeuning
Non-alcoholic fatty liver disease (NAFLD), characterized by triglyceride deposition in hepatocytes due to imbalanced lipid homeostasis, is of increasing concern in Western countries, with progression to non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a complex, mutual influence of hepatic fat accumulation, NASH-related inflammatory mediators, and drug-sensing receptors regulating xenobiotic metabolism. Here, we investigated the suitability of human HepaRG hepatocarcinoma cells as a model for NAFLD and NASH...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29329425/comparison-of-hepatic-2d-sandwich-cultures-and-3d-spheroids-for-long-term-toxicity-applications-a-multi-center-study
#3
Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris Goldring, Kevin Park, Sophie Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Primary human hepatocytes (PHH) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHH are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the six participating laboratories evaluated the robustness of these two model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-lab variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms...
January 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29328380/role-of-the-pi3k%C3%A2-akt%C3%A2-mtor-pathway-in-hepatitis-b-virus-infection-and-replication
#4
Kunlun Xiang, Bin Wang
The replication of hepatitis B virus (HBV) may be modulated by a variety of cell signaling pathways, including the phosphatidylinositol 3‑kinase (PI3K)‑RAC‑α serine/threonine‑protein kinase (AKT)‑serine/threonine‑protein kinase mTOR (mTOR) pathway. The aim of the present study was to determine the regulatory effects of this pathway on the infection and replication of HBV. The results indicated that the HBV entry process may activate the AKT pathway, as demonstrated by AKT phosphorylation in HBV natural infection...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321828/exendin-4-protects-mice-from-d-galactose-induced-hepatic-and-pancreatic-dysfunction
#5
Akram Ahangarpour, Ali Akbar Oroojan, Mohammad Badavi
Investigations into pharmaceutical intervention of pancreatic and hepatic dysfunction associated with metabolic disturbances have received relatively little attention. The aim of this study was to investigate the protective effects of exendin-4 in mice receiving D-galactose, a reducing sugar that triggers ROS production and inflammatory mediators affecting the pancreas and liver. Exendin-4 is an United States Food and Drug Administration (FDA) approved glucagon-like peptide that increases insulin dependent glycogen synthesis and glucose uptake...
2018: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/29316579/-management-of-compensated-liver-cirrhosis-2018-evidence-based-prophylactic-measures
#6
Kathrin Karkmann, Felix Piecha, Anna Caterina Rünzi, Lisa Schulz, Moritz von Wulffen, Daniel Benten, Johannes Kluwe, Henning Wege
In 2015, more than 13 000 people died due to the consequences of liver cirrhosis in Germany. Frequently, relevant liver fibrosis is diagnosed by non-invasive methods (e. g., ultrasound-based measurement of liver stiffness) already in the compensated stage. Following diagnosis of liver fibrosis, a thorough investigation of the underlying chronic liver disease and effective treatment are important to prevent progression to decompensated cirrhosis. Since morbidity and mortality dramatically increase in the decompensated stage (patients may present with jaundice, ascites, hepatic encephalopathy, gastrointestinal bleeding) with an upsurge in 1-year-mortality from 1 - 3...
January 2018: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29313295/radiation-preparation-of-l-arginine-acrylic-acid-hydrogel-matrix-patch-for-transdermal-delivery-of-propranolol-hcl-in-hypertensive-rats
#7
Rasha R Radwan, Heba A Mohamed, H E Ali, Ghada A Mahmoud
In the present study, L-arginine/acrylic acid (Arg/AAc) batch hydrogel was successfully prepared by gamma irradiation for transdermal delivery of propranolol HCl in hypertensive rats. The resulted system has been characterized by FTIR to confirm the hydrogel formation. The swelling behavior of the prepared hydrogels was investigated as a function of time and pH. The kinetics of swelling has been investigated. In vivo pharmacokinetics evaluation, skin irritation test, and histopathological studies were investigated...
January 8, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29313261/enhancement-of-in-vivo-efficacy-and-oral-bioavailability-of-aripiprazole-with-solid-lipid-nanoparticles
#8
Silki, Vivek Ranjan Sinha
Aripiprazole (ARP), a second-generation or atypical antipsychotic, is poorly soluble and undergoes extensive hepatic metabolism and P-glycoprotein efflux which lead to reduced in vivo efficacy and increased dose-related side effects. To enhance in vivo efficacy and oral bioavailability of aripiprazole, aripiprazole-loaded solid lipid nanoparticles (SLNs) were developed using tristearin as solid lipid. Tween 80 and sodium taurocholate were used as surfactants to prepare SLNs using microemulsification method...
January 8, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29310474/low-prevalence-of-hepatitis-e-in-iceland-a-seroepidemiological-study
#9
Arthur Löve, Thora B Björnsdottir, Sigurdur Olafsson, Einar S Björnsson
OBJECTIVE: Hepatitis E virus (HEV) infection has been reported to be more prevalent in the developed countries than previously thought. HEV infection is an important differential diagnosis in patients with drug-induced liver injury (DILI). The prevalence of hepatitis E was investigated in the general population of Iceland, among pig farmers and patients with DILI. MATERIALS AND METHODS: Serum samples were tested for hepatitis E IgG, with two commercial ELISA tests: Diagnostic Bioprobes Srl...
January 8, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29310059/human-induced-pluripotent-stem-cell-line-with-cytochrome-p450-enzyme-polymorphism-cyp2c19-2-cyp3a5-3c-generated-from-lymphoblastoid-cells
#10
Jaehun Lee, Dong-Hun Woo, Han-Jin Park, Kijung Park, Duck Sung Ko, Jong-Hoon Kim
Cytochrome P450 (CYP) comprises a superfamily of monooxygenase responsible for the metabolism of xenobiotics and approximately 75% of drugs in use today. Thus, genetic polymorphisms in CYP genes contribute to interindividual differences in hepatic metabolism of drugs, affecting on individual drug efficacy and may cause adverse effects. Here, we generated a human induced pluripotent stem cell (hiPSC) line with pharmacologically important traits (CYP2C19*2/CYP3A5*3C), which are highly polymorphic in Asian from lymphoblastoid cells...
December 23, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29309877/development-of-a-mechanistic-biokinetic-model-for-hepatic-bile-acid-handling-to-predict-possible-cholestatic-effects-of-drugs
#11
Sylvia Notenboom, Karl M Weigand, Johannes H Proost, Marola M van Lipzig, Evita van de Steeg, Petra H H van den Broek, Rick Greupink, Frans G M Russel, Geny M M Groothuis
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic) intrahepatic concentrations of bile acids with subsequent cell injury. In order to investigate the possibilities for in silico prediction of cholestatic effects of drugs, we developed a mechanistic biokinetic model for human liver bile acid handling populated with human in vitro data...
January 5, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29309148/identification-of-factors-promoting-hbv-capsid-self-assembly-by-assembly-promoting-antivirals
#12
Soumya Lipsa Rath, Huihui Liu, Susumu Okazaki, Wataru Shinoda
Around 270 million individuals currently live with Hepatitis B Virus (HBV) infection. Heteroaryldihydropyrimidines (HAPs) are a family of antivirals that target the HBV capsid protein and induce aberrant self-assembly. The capsids formed resemble the native capsid structure, but are unable to propagate the virus progeny due to lack of RNA/DNA. Under normal conditions, self-assembly is initiated by the viral genome. The mode of action of HAPs, however, remains largely unknown. Here, using molecular dynamics simulations, we attempted to understand HAP action by comparing the dynamics of capsid proteins with and without HAPs...
January 8, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29301090/evaluation-of-therapeutic-effect-of-rice-husk-silica-combined-with-platelets-derived-growth-factor-in-hepatic-veno-occlusive-disease
#13
Eithar K Al Adham, Amal I Hassan, M M Hazem, Ahmed Shebl
Veno- occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study aimed to investigate the possible therapeutic impact of rice husk silica (RHS) nanoparticles combined with a platelet-derived growth factor (PDGF) on the Veno-occlusive disease in liver (VOD) elicited by dactinomycin (DAC) in rats. Forty-eight male Sprague-Dawely rats were classified into six groups, 8 rats each. The first group served as control, the second, animals were infused by intraperitoneal injection with DAC (0...
January 4, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29300159/self-association-and-conformational-variation-of-ns5a-domain-1-of-hepatitis-c-virus
#14
Serap Beldar, Malathy Sony Subramanian Manimekalai, Nam-Joon Cho, Kwanghee Baek, Gerhard Grüber, Ho Sup Yoon
Direct-acting antivirals (DAAs) targeting the non-structural 5A (NS5A) protein of the hepatitis C virus (HCV) are crucial drugs that have shown exceptional clinical success in patients. However, their mode of action (MoA) remains unclear, and drug-resistant HCV strains are rapidly emerging. It is critical to characterize the behaviour of the NS5A protein in solution, which can facilitate the development of new classes of inhibitors or improve the efficacy of the currently available DAAs. Using biophysical methods, including dynamic light scattering, size exclusion chromatography and chemical cross-linking experiments, we showed that the NS5A domain 1 from genotypes 1b and 1a of the HCV intrinsically self-associated and existed as a heterogeneous mixture in solution...
January 4, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29299156/inhibition-of-pi4k-iii%C3%AE-radiosensitizes-in-human-tumor-xenograft-and-immune-competent-syngeneic-murine-tumor-model
#15
Younghee Park, Ji Min Park, Dan Hyo Kim, Jeanny Kwon, In Ah Kim
Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296203/the-pathogenesis-of-diclofenac-induced-immunoallergic-hepatitis-in-a-canine-model-of-liver-injury
#16
Saravanakumar Selvaraj, Jung-Hwa Oh, Reinhard Spanel, Florian Länger, Hyoung-Yun Han, Eun-Hee Lee, Seokjoo Yoon, Jürgen Borlak
Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290620/pharmacological-stimulation-of-p53-with-low-dose-doxorubicin-ameliorates-diet-induced-nonalcoholic-steatosis-and-steatohepatitis
#17
Begoña Porteiro, Marcos F Fondevila, Xabier Buque, Maria J Gonzalez-Rellan, Uxia Fernandez, Alfonso Mora, Daniel Beiroa, Ana Senra, Rosalia Gallego, Johan Fernø, Miguel López, Guadalupe Sabio, Carlos Dieguez, Patricia Aspichueta, Rubén Nogueiras
OBJECTIVE: Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: We used long-term pharmacological activation of p53 by i.p. or oral administration of low-dose doxorubicin in different animal models of NAFLD (high fat diet containing 45% and 60% kcal fat) and NASH (methionine- and choline-deficient diet and choline deficiency combined with high fat diet)...
December 15, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#18
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29289533/ldl-receptor-gene-ablated-hamsters-a-rodent-model-of-familial-hypercholesterolemia-with-dominant-inheritance-and-diet-induced-coronary-atherosclerosis
#19
Xin Guo, Mingming Gao, Yunan Wang, Xiao Lin, Liu Yang, Nathan Cong, Xiangbo An, Feng Wang, Kai Qu, Liqing Yu, Yuhui Wang, Jinjie Wang, Haibo Zhu, Xunde Xian, George Liu
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease caused mainly by LDL receptor (Ldlr) gene mutations. Unlike FH patients, heterozygous Ldlr knockout (KO) mice do not show a dominant FH trait. Hamsters, like humans, have the cholesteryl ester transfer protein, intestine-only ApoB editing and low hepatic cholesterol synthesis. Here, we generated Ldlr-ablated hamsters using CRISPR/Cas9 technology. Homozygous Ldlr KO hamsters on a chow diet developed hypercholesterolemia with LDL as the dominant lipoprotein and spontaneous atherosclerosis...
December 15, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29281794/reduction-and-scavenging-of-chemically-reactive-drug-metabolites-by-nad-p-h-quinone-oxidoreductase-1-and-nrh-quinone-oxidoreductase-2-and-variability-in-hepatic-concentrations
#20
Shalenie P den Braver-Sewradj, Michiel W den Braver, Robin M Toorneman, Stephanie van Leeuwen, Yongjie Zhang, Stefan J Dekker, Nico P E Vermeulen, Jan N M Commandeur, J Chris Vos
Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug bioactivation to chemically reactive drug metabolites. In the current study, we quantified the concentrations of NQO1 and NQO2 in 20 human liver donors and NQO1 and NQO2 activities with quinone-like drug metabolites. Hepatic NQO1 concentrations ranged from 8 to 213 nM...
December 27, 2017: Chemical Research in Toxicology
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