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Drug induced hepatitis

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https://www.readbyqxmd.com/read/28440736/levistilide-a-inhibits-angiogenesis-in-liver-fibrosis-via-vascular-endothelial-growth-factor-signaling-pathway
#1
Zhi-Min Zhao, Hong-Liang Liu, Xin Sun, Tao Guo, Li Shen, Yan-Yan Tao, Cheng-Hai Liu
Levistilide A (C24H28O4, molecular weight = 380.48) derived from Angelica sinensis (Danggui) has been reported to inhibit hepatic stellate cell proliferation. This study investigated the effects of levistilide A on liver fibrosis relating to angiogenesis, particularly on the characteristic change in liver sinusoidal endothelial cells. LX-2 cells were activated by TGF-β1, and the human hepatic sinusoidal endothelial cells (HHSECs) were induced by endothelial cell growth supplement. Cell viability was detected using a methylthiazoldiphenyl-tetrazolium bromide assay; F-actin was visualized through the fluorescence probe method; cell proliferation was examined using the EdU kit; antiangiogenesis activity was assessed using the tube formation assay and transgenic zebrafish model...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28438781/transporter-mediated-disposition-clinical-pharmacokinetics-and-cholestatic-potential-of-glyburide-and-its-primary-active-metabolites
#2
Rui Li, Yi-An Bi, Anna Vildhede, Renato J Scialis, Sumathy Mathialagan, Xin Yang, Lisa D Marroquin, Jian Lin, Manthena V S Varma
Glyburide is widely used for the treatment of type 2 diabetes mellitus. We studied the mechanisms involved in the disposition of glyburide and its pharmacologically active hydroxy metabolites, M1 and M2b; and evaluated their clinical pharmacokinetics and the potential role in glyburide-induced cholestasis employing physiologically based pharmacokinetic (PBPK) modeling. Transport studies of parent and metabolites in human hepatocytes and transfected cell systems imply hepatic uptake mediated by organic anion transporting polypeptides...
April 24, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28438569/methylprednisolone-liver-toxicity-a-new-case-and-a-french-regional-pharmacovigilance-survey
#3
Jérôme Dumortier, Judith Cottin, Caroline Lavie, Olivier Guillaud, Valérie Hervieu, Christine Chambon-Augoyard, Jean-Yves Scoazec, Sandra Vukusic, Thierry Vial
Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug...
April 21, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28438436/effects-of-dextran-sulfate-sodium-induced-experimental-colitis-on-cytochrome-p450-activity-in-rat-liver-kidney-and-intestine
#4
Nan Hu, Yanjuan Huang, Xuejiao Gao, Sai Li, Zhixiang Yan, Bin Wei, Ru Yan
Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs) have been reported in this model and patients with UC. In this study, six CYPs activities were quantitatively determined in microsomes of liver (RLMs), kidney (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days, UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases and compared with normal rats. Generally, CYPs activities varied with isoform, organ, and disease status...
April 21, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28437842/autoimmune-like-chronic-hepatitis-induced-by-olmesartan
#5
Sandrine Barge, Marianne Ziol, Jean-Charles Nault
Drug liver-induced injury (DILI) due to minocyclin, alpha methyldopa or nitrofurantoin may be responsible for chronic liver damage that mimic the biological and/or histological features of chronic autoimmune hepatitis and, in rare cases, progresses to cirrhosis(1). Olmesartan medoxomil is an antihypertensive drug that acts by blocking the angiotensin II receptor and is metabolized into its pharmacologically active form, olmesartan, in the intestine and in the liver before being released into the systemic circulation...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28434905/using-quantitative-intravital-multiphoton-microscopy-to-dissect-hepatic-transport-in-rats
#6
Kenneth W Dunn, Jennifer C Ryan
Hepatic solute transport is a complex process whose disruption is associated with liver disease and drug-induced liver injury. Intravital multiphoton fluorescence excitation microscopy provides the spatial and temporal resolution necessary to characterize hepatic transport at the level of individual hepatocytes in vivo and thus to identify the mechanisms and cellular consequences of cholestasis. Here we present an overview of the use of fluorescence microscopy for studies of hepatic transport in living animals, and describe how we have combined methods of intravital microscopy and digital image analysis to dissect the effects of drugs and pathological conditions on the function of hepatic transporters in vivo...
April 20, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28434881/muramyl-dipeptide-based-postbiotics-mitigate-obesity-induced-insulin-resistance-via-irf4
#7
Joseph F Cavallari, Morgan D Fullerton, Brittany M Duggan, Kevin P Foley, Emmanuel Denou, Brennan K Smith, Eric M Desjardins, Brandyn D Henriksbo, Kalvin J Kim, Brian R Tuinema, Jennifer C Stearns, David Prescott, Philip Rosenstiel, Brian K Coombes, Gregory R Steinberg, Jonathan D Schertzer
Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome...
April 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28433925/low-dose-pollutant-mixture-triggers-metabolic-disturbances-in-female-mice-leading-to-common-and-specific-features-as-compared-to-a-high-fat-diet
#8
Emmanuel Labaronne, Claudie Pinteur, Nathalie Vega, Sandra Pesenti, Benoit Julien, Emmanuelle Meugnier-Fouilloux, Hubert Vidal, Danielle Naville, Brigitte Le Magueresse-Battistoni
Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic disturbances triggered in nonobese mice lifelong exposed to a mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine, polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were compared with changes provoked by a high-fat high-sucrose (HFHS) diet not containing the pollutant mixture...
April 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#9
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28430612/diosmetin-exerts-anti-oxidative-anti-inflammatory-and-anti-apoptotic-effects-to-protect-against-endotoxin-induced-acute-hepatic-failure-in-mice
#10
You Yang, Xiao-Bao Gong, Li-Gua Huang, Zhen-Xu Wang, Rong-Zhen Wan, Peng Zhang, Qing-Yan Zhang, Zhu Chen, Bao-Shun Zhang
To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged free radicals. In vivo, diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#11
Caroline E Geisler, Benjamin Jennings Renquist
Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28428116/cycloastragenol-improves-hepatic-steatosis-by-activating-farnesoid-x-receptor-signalling
#12
Ming Gu, Shiying Zhang, Yuanyuan Zhao, Jinwen Huang, Yahui Wang, Yin Li, Shengjie Fan, Li Yang, Guang Ji, Qingchun Tong, Cheng Huang
Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28427912/hepataprotective-effects-of-ginsenoside-rg1-a-review
#13
REVIEW
Yan Gao, Shifeng Chu, Zhao Zhang, Naihong Chen
BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng has been used as efficient tonic and for the treatment of various diseases including hepatic disorders. Ginseng saponins, also known as ginsenosides, are principal constituents and have been treated to be responsible for disparate ginseng health benefits. The current review mainly focuses on ginsenoside Rg1, a compound isolated from traditional Chinese herbal medicine Panax ginseng Meyer. AIMS: To summary the hepataprotective effects and related mechanisms of ginsenoside Rg1, we conclude this review by combining the literature and our own researches...
April 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28426815/using-controlled-attenuation-parameter-combined-with-ultrasound-to-survey-non-alcoholic-fatty-liver-disease-in-hemodialysis-patients-a-prospective-cohort-study
#14
Yi-Hao Yen, Jin-Bor Chen, Ben-Chung Cheng, Jung-Fu Chen, Kuo-Chin Chang, Po-Lin Tseng, Cheng-Kun Wu, Ming-Chao Tsai, Ming-Tsung Lin, Tsung-Hui Hu
BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the leading cause of morbidity and mortality in hemodialysis patients. The aim of this study was to investigate the prevalence of NAFLD in hemodialysis patients. METHOD: We prospectively enrolled patients undergoing chronic hemodialysis, as well as patients with normal renal function who served as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28425858/nano-encapsulation-of-dietary-phytoconstituent-capsaicin-on-emulsome-evaluation-of-anticancer-activity-through-the-measurement-of-liver-oxidative-stress-in-rats
#15
Tapan Kumar Giri, Kaustav Pramanik, Tapan Kumar Barman, Subhasis Maity
Protective effects of capsaicin (CAP) loaded nano-emulsomes (EML) was evaluated against the oxidative stress of rat livers induced through sodium fluoride (NaF). EML was prepared by thin film hydration method that is development of thin lipid film followed by hydration and sonication. EML was characterized by Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) techniques. In vitro drug release study of optimized formulation showed that 50% of CAP was released within 50.21 min while 85% CAP was released in 227...
April 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28423574/synergistic-anti-tumor-efficacy-of-sorafenib-and-fluvastatin-in-hepatocellular-carcinoma
#16
Yang Cheng, RongCheng Luo, Hang Zheng, Biao Wang, YaHui Liu, DingLi Liu, JinZhang Chen, WanFu Xu, AiMin Li, Yun Zhu
Drug resistance to sorafenib is common in patients with hepatocellular carcinoma(HCC). We examined the effects of a combination of sorafenib and fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced apoptosis and reduced cellular viability in HCC more effectively than either drug alone. The combination treatment also inhibited activation of hepatic stellate cells, whereas single drug treatments did not. On a molecular level, combined treatment inhibited activation of the MAPK and NF-κB pathways via Toll-like receptor 4 in HCC cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422962/docosahexaenoic-acid-blocks-progression-of-western-diet-induced-nonalcoholic-steatohepatitis-in-obese-ldlr-mice
#17
Kelli A Lytle, Carmen P Wong, Donald B Jump
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28419467/refining-liver-safety-risk-assessment-application-of-mechanistic-modeling-and-serum-biomarkers-to-cimaglermin-alfa-ggf2-clinical-trials
#18
Diane M Longo, Grant T Generaux, Brett A Howell, Scott Q Siler, Daniel J Antoine, Donald Button, Anthony Caggiano, Andrew Eisen, Jennifer Iaci, Ric Stanulis, Tom Parry, Merrie Mosedale, Paul B Watkins
Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in development for heart failure. Phase 1 trials were suspended when 2 cimaglermin alfa-treated subjects experienced concomitant elevations in serum aminotransferases and total bilirubin meeting current FDA criteria for a serious liver safety signal (i.e. "Hy's Law"). We assayed mechanistic biomarkers in archived clinical trial serum samples which confirmed the hepatic origin of the aminotransferase elevations in these two subjects and identified apoptosis as the major mode of hepatocyte death...
April 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28417920/evaluation-of-the-potential-risk-of-drugs-to-induce-hepatotoxicity-in-human-relationships-between-hepatic-steatosis-observed-in-non-clinical-toxicity-study-and-hepatotoxicity-in-humans
#19
Keisuke Goda, Akio Kobayashi, Akemi Takahashi, Tadakazu Takahashi, Kosuke Saito, Keiko Maekawa, Yoshiro Saito, Shoichiro Sugai
In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#20
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
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