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Drug induced hepatitis

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https://www.readbyqxmd.com/read/28077314/biological-or-pharmacological-activation-of-protein-kinase-c-alpha-constrains-hepatitis-e-virus-replication
#1
Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrera Carrillo, Johannes H Brandsma, Raymond A Poot, Ben Berkhout, Johan Neyts, Maikel P Peppelenbosch, Qiuwei Pan
Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication...
January 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#2
Kyunghee Yang, Christina Battista, Jeffrey L Woodhead, Simone H Stahl, Jerome T Mettetal, Paul B Watkins, Scott Q Siler, Brett A Howell
Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Using physiologically-based pharmacokinetic model-predicted drug exposure and enzyme/transporter inhibition constants determined in vitro, our model correctly predicted indinavir-mediated hyperbilirubinemia in humans and rats...
January 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28070697/development-of-a-dsred-expressing-heparg-cell-line-for-real-time-monitoring-of-hepatocyte-like-cell-differentiation-by-fluorescence-imaging-with-application-in-screening-of-novel-geometric-microstructured-cell-growth-substrates
#3
Mihaela Uta, Livia E Sima, Patrik Hoffmann, Valentina Dinca, Norica Branza-Nichita
The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cells. Cell treatment with specific differentiation inducers results in a mixture of hepatocyte- and biliary-like cells, accompanied by upregulation of liver-specific proteins, drug metabolizing enzymes, transcription regulators, membrane receptors or innate immune response effectors. These features make the HepaRG cells a suitable and handy replacement for primary hepatocytes, to study hepatic functions in vitro. However, cell differentiation is a long, variable process, requiring special culture conditions, while the resulting mixed cell populations is usually a major drawback...
March 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28068634/virgin-coconut-oil-supplementation-attenuates-acute-chemotherapy-hepatotoxicity-induced-by-anticancer-drug-methotrexate-via-inhibition-of-oxidative-stress-in-rats
#4
Ademola C Famurewa, Odomero G Ufebe, Chima A Egedigwe, Onyebuchi E Nwankwo, Godwin S Obaje
BACKGROUND: The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. METHODS: Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28064130/a-new-endoplasmic-reticulum-targeted-two-photon-fluorescent-probe-for-imaging-of-superoxide-anion-in-diabetic-mice
#5
Haibin Xiao, Xiao Liu, Chuanchen Wu, Yaohuan Wu, Ping Li, Xiaomeng Guo, Bo Tang
Excessive or unfolded proteins accumulation in endoplasmic reticulum (ER) will cause ER stress, which has evolved to involve in various metabolic diseases. In particular, ER stress plays an important role in the pathogenesis of diabetes. Both ER stress and course of diabetes accompany oxidative stress and production of reactive oxygen species (ROS), among which superoxide anion (O2(•-)) is the first produced ROS and has been recognized as cell signaling mediator involved in the physiological and pathological process of diabetes...
December 31, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28062541/evaluation-of-a-novel-renewable-hepatic-cell-model-for-prediction-of-clinical-cyp3a4-induction-using-a-correlation-based-ris-approach
#6
Rongjun Zuo, Feng Li, Sweta Parikh, Li Cao, Kirsten L Cooper, Yulong Hong, Jin Liu, Ronald A Faris, Daochuan Li, Hongbing Wang
Metabolism enzyme induction-mediated drug-drug interactions need to be carefully characterized in vitro for drug candidates in order to predict in vivo outcomes of safety risk and therapeutic efficiency. Currently, both the FDA and EMA recommend using primary human hepatocytes as the "Gold Standard" in vitro test system for studying the induction potential of candidate drugs on cytochrome P450 (CYP), CYP3A4, CYP1A2, and CYP2B6. However, primary human hepatocytes are known to bear inherent limitations such as limited supply and large lot-to-lot variations which result in an experimental burden to qualify new lots...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28058783/characterization-of-phase-i-and-phase-ii-hepatic-metabolism-and-reactive-intermediates-of-larrea-nitida-cav-and-its-lignan-compounds
#7
Hyesoo Jeong, Soolin Kim, Jimin Lee, Jin Young Park, Wenmei Zhou, Xiyuan Liu, So Dam Kim, Yun Seon Song, Chang-Young Jang, Sei-Ryang Oh, Sangho Choi, Minsun Chang
Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America to treat various pathological conditions. It contains the antioxidant and antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well as O-methylated metabolite of NDGA (MNDGA) as bioactive compounds. The hepatic metabolism-based toxicological potential of extracts of LNC (LNE), NDGA, and MNDGA has not previously been reported. The present study aimed to characterize the phase I and phase II hepatic metabolism and reactive intermediates of LNE, NDGA, and MNDGA and their effects on the major drug-metabolizing enzymes in vitro and ex vivo...
January 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28056551/hepatitis-b-x-interacting-protein-promotes-cisplatin-resistance-and-regulates-cd147-via-sp1-in-ovarian-cancer
#8
Wei Zou, Xiangdong Ma, Hong Yang, Wei Hua, Biliang Chen, Guoqing Cai
Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28051995/in-vitro-modelling-of-familial-amyloidotic-polyneuropathy-allows-quantitative-detection-of-transthyretin-amyloid-fibril-like-structures-in-hepatic-derivatives-of-patient-specific-induced-pluripotent-stem-cells
#9
Jeannine Hoepfner, Mandy Kleinsorge, Oliver Papp, Susanne Alfken, Robin Heiringhoff, Andreas Pich, Vanessa Sauer, Andree Zibert, Gudrun Göhring, Hartmut Schmidt, Malte Sgodda, Tobias Cantz
The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related Familial Amyloidotic Polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies...
January 4, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28051834/interferon-%C3%AE-induced-protein-10-in-dengue-virus-infection
#10
P Fallahi, G Elia
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Interferons (IFNs), and IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ-induced protein 10 (IP-10), CXCL9/MIG and CXCL11/I-TAC, and their common receptor chemokine (C-X-C motif) receptor (CXCR)3 are induced by DENV infection; however it has been shown that the latter two could not compensate for the absence of IP-10. This paper reviews studies about DENV and IP-10. Evidences show the importance of IP-10 induction during DENV infection, in macrophages, lymphocytes, hepatic cells, denritic cells, in skin and in the brain...
November 2016: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28044452/nitric-oxide-mediates-effects-of-acute-not-chronic-naltrexone-on-lps-induced-hepatic-encephalopathy-in-cirrhotic-rats
#11
Bentolhoda Ghiassy, Nastaran Rahimi, Mehrak Javadi-Paydar, Mohammad Hadi Gharedaghi, Abbas Norouzi-Javidan, Ahmad R Dehpour
Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i...
January 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28042884/pharmacokinetics-of-the-antimicrobial-drug-sulfanilamide-is-altered-in-a-preclinical-model-of-vascular-calcification
#12
Anabel Brandoni, Adriana Mónica Torres
In vascular smooth muscle, calcium overload is linked to advancing age. The pharmacokinetics of sulfanilamide (SA), a compound with antibacterial properties, was evaluated in a preclinical model of vascular calcification. SA was used since it is useful to study possible modifications in the renal and hepatic management of drugs. Vascular calcification was induced by administration of a single high dose of vitamin D3 to rats (treated group) 10 days before the experiments. A parallel control group was processed...
January 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28042834/phlorotannins-towards-new-pharmacological-interventions-for-diabetes-mellitus-type-2
#13
REVIEW
Graciliana Lopes, Paula B Andrade, Patrícia Valentão
Diabetes mellitus is a group of metabolic disorders characterized by hyperglycaemia, and predicted by the World Health Organization as the expected 7th leading cause of death in 2030. Diabetes mellitus type 2 (DMT2) comprises the majority of diabetic individuals around the world (90%-95%). Pathophysiologically, this disorder results from a deregulation of glucose homeostasis, worsened by overweight and by a sedentary lifestyle, culminating in life-threatening cardiovascular events. The currently available anti-diabetic drugs are not devoid of undesirable side effects, sometimes responsible for poor therapeutic compliance...
December 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28039473/nanometronomic-treatment-of-4t1-breast-cancer-with-nanocaged-doxorubicin-prevents-drug-resistance-and-circumvents-cardiotoxicity
#14
Serena Mazzucchelli, Michela Bellini, Luisa Fiandra, Marta Truffi, Maria A Rizzuto, Luca Sorrentino, Erika Longhi, Manuela Nebuloni, Davide Prosperi, Fabio Corsi
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, "metronomic" chemotherapy is based on frequent drug administrations at lower doses, resulting in neovascularization inhibition and induction of tumor dormancy. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035999/spectroscopic-studies-on-the-molecular-ageing-of-serum-albumin
#15
Mariola Chudzik, Małgorzata Maciążek-Jurczyk, Bartosz Pawełczak, Anna Sułkowska
Pathological states in the organism, e.g., renal or hepatic diseases, cataract, dysfunction of coronary artery, diabetes mellitus, and also intensive workout, induce the structural modification of proteins called molecular ageing or N-A isomerization. The aim of this study was to analyze the structural changes of serum albumin caused by alkaline ageing using absorption, spectrofluorescence, and circular dichroism spectroscopy. The N-A isomerization generates significant changes in bovine (BSA) and human (HSA) serum albumin subdomains-the greatest changes were observed close to the tryptophanyl (Trp) and tyrosyl (Tyr) residue regions while a smaller change was observed in phenyloalanine (Phe) environment...
December 27, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28035197/evolving-new-strategies-for-the-medical-management-of-chronic-hepatitis-b-virus-infection
#16
Timothy M Block, Tianlun Zhou, Nikhil Anbarasan, Robert Gish
Is a cure for chronic hepatitis B virus (HBV) infection possible? Hepatitis C virus infection is now routinely cured medically. There is a growing expectation that new drugs for the management of chronic HBV infection should provide substantial benefit over and above that of current chronic HBV medications, if not be curative. Although the definition of medically induced cure for chronic HBV infection varies, most include sustained off-drug absence of viremia and negativity for other virologic markers. There are currently more than 29 drugs in the pipeline being tested for the management of chronic HBV infection...
November 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28031524/adenosine-5-monophosphate-blocks-acetaminophen-toxicity-by-increasing-ubiquitination-mediated-ask1-degradation
#17
Xiao Yang, Yibei Zhan, Qi Sun, Xi Xu, Yi Kong, Jianfa Zhang
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the world. Hepatic c-jun NH2-terminal protein kinase (JNK) activation is thought to be a consequence of oxidative stress produced during APAP metabolism. Activation of JNK signals causes hepatocellular damage with necrotic and apoptotic cell death. Here we found that APAP caused a feedback increase in plasma adenosine 5'-monophsphate (5'-AMP). We demonstrated that co-administration of APAP and 5'-AMP significantly ameliorated APAP-induced hepatotoxicity in mice, without influences on APAP metabolism and its analgesic function...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031486/structural-basis-for-regiospecific-midazolam-oxidation-by-human-cytochrome-p450-3a4
#18
Irina F Sevrioukova, Thomas L Poulos
Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzyme that oxidizes more than 60% of administered therapeutics. Knowledge of how CYP3A4 adjusts and reshapes the active site to regioselectively oxidize chemically diverse compounds is critical for better understanding structure-function relations in this important enzyme, improving the outcomes for drug metabolism predictions, and developing pharmaceuticals that have a decreased ability to undergo metabolism and cause detrimental drug-drug interactions...
December 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28029729/combination-treatment-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-nondiabetic-rat-model-of-steatohepatitis
#19
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Saikawa Soichiro, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we demonstrated that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (ARB: losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of nondiabetic nonalcoholic steatohepatitis (NASH) in a rat model...
December 28, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28029125/ameliorative-effect-of-curcumin-encapsulated-hyaluronic-acid-pla-nanoparticles-on-thioacetamide-induced-murine-hepatic-fibrosis
#20
Yu-Nong Chen, Shih-Lan Hsu, Ming-Yuan Liao, Yi-Ting Liu, Chien-Hung Lai, Ji-Feng Chen, Mai-Huong Thi Nguyen, Yung-Hsiang Su, Shang-Ting Chen, Li-Chen Wu
In this study, we developed curcumin-encapsulated hyaluronic acid-polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs...
December 24, 2016: International Journal of Environmental Research and Public Health
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