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Drug-induced liver disease

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https://www.readbyqxmd.com/read/28649126/cis-stilbene-glucoside-in-polygonum-multiflorum-induces-immunological-idiosyncratic-hepatotoxicity-in-lps-treated-rats-by-suppressing-ppar-%C3%AE
#1
Ya-Kun Meng, Chun-Yu Li, Rui-Yu Li, Lan-Zhi He, He-Rong Cui, Ping Yin, Cong-En Zhang, Peng-Yan Li, Xiu-Xiu Sang, Ya Wang, Ming Niu, Ya-Ming Zhang, Yu-Ming Guo, Rong Sun, Jia-Bo Wang, Zhao-Fang Bai, Xiao-He Xiao
The root of Polygonum multiflorum Thunb (PM) has been used in China to treat a variety of diseases, such as constipation, early graying of the hair and hyperlipemia. Recent evidence shows that PM causes idiosyncratic drug-induced liver injury (IDILI) in humans. In this study, we investigated the molecular basis of PM-induced liver injury in a rat model of IDILI based on a non-hepatotoxic dose of LPS. SD rats were orally administered 3 potentially hepatotoxic compounds of PM: cis-stilbene glucoside (cis-SG, 50 mg/kg), trans-SG (50 mg/kg) or emodin (5 mg/kg), followed by injection of LPS (2...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28649077/hepatoprotective-evaluation-of-aqueous-ethanolic-extract-of-capparis-decidua-stems-in-paracetamol-induced-hepatotoxicity-in-experimental-rabbits
#2
Jalilur Rehman, Naveed Akhtar, Hafiz Muhammad Asif, Sabira Sultana, Mukhtiar Ahmad
Liver diseases are the most common ailment all over the world mostly caused by viruses, toxic chemicals, excessive intake of alcohol, high doses of paracetamol, carbon tetrachloride, chemotherapeutic agents and peroxides oil, etc. There is a great need to assess the scientific basis for the medicinal plants that are claimed to have hepatoprotective activity. We investigate the hepatoprotective effects of aqueous-ethanolic extract of Capparis decidua (Stems) against paracetamol induced liver injury in experimental animals...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28647568/hepatocyte-derived-macrophage-migration-inhibitory-factor-mediates-alcohol-induced-liver-injury-in-mice-and-patients
#3
Veronica Marin, Kyle Poulsen, Gemma Odena, Megan R McMullen, Jose Altamirano, Pau Sancho-Bru, Claudio Tiribelli, Juan Caballeria, Natalia Rosso, Ramon Bataller, Laura E Nagy
BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) is a multi-potent cytokine that contributes to the inflammatory response to injury. MIF is expressed by multiple cell types; however, the cellular source and actions of MIF in alcoholic liver disease (ALD) are not well known. Here we tested the hypothesis that non-myeloid cells, specifically hepatocytes, are an important cellular source of MIF in ALD. METHODS: MIF expression was measured in HuH7 and differentiated THP-1 cells in response to ethanol...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#4
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28646549/inhibition-of-jnk-signaling-mediates-ppar%C3%AE-dependent-protection-against-intrahepatic-cholestasis-by-fenofibrate
#5
Manyun Dai, Julin Yang, Minzhu Xie, Jiao Lin, Min Luo, Huiying Hua, Gangming Xu, Hante Lin, Danjun Song, Yuqing Cheng, Bin Guo, Jinshun Zhao, Frank J Gonzalez, Aiming Liu
BACKGROUND AND PURPOSE: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for the treatment of hyperlipidemia. Although fibrate drugs were reported to be beneficial for cholestasis, the underlying mechanism has not been determined. EXPERIMENTAL APPROACH: Wild-type mice and Pparα-null mice were orally pretreated with fenofibrate for three days, following which ANIT was administered to induce cholestasis. The potent experimental PPARα agonist WY14643 was used to validate the role of PPARα, and the JNK inhibitor SP600125 was employed to explore the role of the JNK pathway in cholestatic liver injury...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#6
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#7
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28640507/a-liver-specific-gene-expression-panel-predicts-the-differentiation-status-of-in-vitro-hepatocyte-models
#8
Dae-Soo Kim, Jea-Woon Ryu, Mi-Young Son, Jung-Hwa Oh, Kyung-Sook Chung, Sugi Lee, Jeong-Ju Lee, Jun-Ho Ahn, Ju-Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho-Rok Jung, Nam-Soon Kim, Hyun-Soo Cho
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies...
June 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28638862/raw-rehmannia-radix-polysaccharide-can-effectively-release-peroxidative-injury-induced-by-duck-hepatitis-a-virus
#9
Meiyun Song, Yun Chen, Hongxu Du, Shuaibing Zhang, Yixuan Wang, Ling Zeng, Jingjing Yang, Jintong Shi, Yi Wu, Deyun Wang, Yuanliang Hu, Jiaguo Liu
BACKGROUND: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH. MATERIALS AND METHODS: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#10
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#11
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28624425/antiobesity-antioxidant-and-hepatoprotective-effects-of-diallyl-trisulphide-dats-alone-or-in-combination-with-orlistat-on-hfd-induced-obese-rats
#12
Sivakumar Annamalai, Lavanya Mohanam, Veena Raja, Alwin Dev, Venkataraman Prabhu
The increasing rate of obesity in the past years has become a worldwide concern and it causes many diseases. Even though, Orlistat, a synthetic anti-obesity drug approved by FDA, it causes severe side effects. DATS, a natural product from garlic have gained attention in many biological activities. The aim of the study is to determine the impact of Dially trisulpide (DATS) and its combination with Orlistat therapy on obese animals. 30 male Wistar rats (150-180g) were assigned into 5 groups (n=6). Group 1 rats received normal diet and Group 2 fed with high fat diet (HFD) for 14 weeks...
June 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28617435/interaction-between-autophagy-and-senescence-is-required-for-dihydroartemisinin-to-alleviate-liver-fibrosis
#13
Zili Zhang, Zhen Yao, Shifeng Zhao, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Autophagy and cellular senescence are stress responses essential for homeostasis. Therefore, they may represent new pharmacologic targets for drug development to treat diseases. In this study, we sought to evaluate the effect of dihydroartemisinin (DHA) on senescence of activated hepatic stellate cells (HSCs), and to further elucidate the underlying mechanisms. We found that DHA treatment induced the accumulation of senescent activated HSCs in rat fibrotic liver, and promoted the expression of senescence markers p53, p16, p21 and Hmga1 in cell model...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28612667/all-that-glitters-yellow-is-not-gold-presentation-and-pathophysiology-of-bile-cast-nephropathy
#14
Mitchell Pitlick, Prerna Rastogi
BACKGROUND: Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28612634/lysosomal-acid-lipase-deficiency-a-form-of-non-obese-fatty-liver-disease-nofld
#15
H H A-Kader
With the growing obesity epidemic, nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the leading causes of liver disease worldwide. Although obesity is a main risk factor for the development of NAFLD, it can also develop in lean subjects and can be encountered in different clinical setting and in association with an array of genetic, metabolic, nutritional, infectious and drug-induced disorders. Areas covered: This article discusses causes of fatty liver in non-obese subjects focusing on Lysosomal acid lipase deficiency (LAL-D), a commonly overlooked disorder reviewing its prevalence, genetics, pathogenesis, clinical features, diagnosis and treatment...
June 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#16
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16(Ink4a)-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#17
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#18
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28602867/effect-of-gangjihwan-on-hepatic-steatosis-and-inflammation-in-high-fat-diet-fed-mice
#19
Jong Seong Roh, Haerim Lee, Jonghoon Lim, Jeongjun Kim, Heejung Yang, Yooshik Yoon, Soon Shik Shin, Michung Yoon
ETHNOPHARMACOLOGICAL RELEVANCE: Gangjihwan (DF), a polyherbal drug composed of Ephedra intermedia Schrenk et C. A. Mayer (Ephedraceae), Lithospermum erythrorhizon Siebold et Zuccarini (Borraginaceae), and Rheum palmatum L. (Polygonaceae), is used to treat obesity in local Korean clinics. The constituents of DF have traditionally been reported to exert anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) effects. Thus, we investigated the effects of DF on obesity and NAFLD and the underlying mechanisms...
June 8, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28596111/high-fat-diet-disrupts-endoplasmic-reticulum-calcium-homeostasis-in-the-rat-liver
#20
Emily S Wires, Kathleen A Trychta, Susanne Bäck, Agnieszka Sulima, Kenner C Rice, Brandon K Harvey
BACKGROUND & AIMS: Disruption to endoplasmic reticulum (ER) calcium homeostasis has been implicated in obesity, however, the ability to longitudinally monitor ER calcium fluctuations has been challenging with prior methodologies. We recently described the development of a Gaussia luciferase (GLuc)- based reporter protein responsive to ER calcium depletion (GLuc-SERCaMP) and investigated the effect of a high fat diet on ER calcium homeostasis. METHODS: A GLuc-based reporter cell line was treated with palmitate, a free fatty acid (FFA)...
June 5, 2017: Journal of Hepatology
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