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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#1
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890005/mechanism-based-inhibitors-from-phytomedicine-risks-of-hepatotoxicity-and-their-potential-hepatotoxic-substructures
#2
Lili Wang, Xin He, Chunhuan Jin, Gregory Ondieki
The adverse reactions and side effects associated with use of herbal medicines, especially their damaging effects on the liver have increasingly been reported worldwide. Some of the herbal ingredients have the potential risk of herb-induced liver injury but their hepatotoxicity mechanisms and associated risk factors are not well characterized until now. Xenobiotics are catalyzed by cytochrome P450 enzymes into highly reactive metabolites, which can covalently bind to the enzyme itself and subsequently cause mechanism-based inhibition (MBI)...
November 23, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27861792/drug-induced-liver-injury-advances-in-mechanistic-understanding-that-will-inform-risk-management
#3
Merrie Mosedale, Paul B Watkins
Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie the hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27847209/in-vivo-study-for-anti-hyperglycemic-potential-of-aqueous-extract-of-basil-seeds-ocimum-basilicum-linn-and-its-influence-on-biochemical-parameters-serum-electrolytes-and-haematological-indices
#4
Sachin Chaudhary, Amit Semwal, Hitesh Kumar, Harish Chandra Verma, Amit Kumar
The study introduced anti-hyperglycemic influence of aqueous extract of Ocimum basilicum seeds (AEOBS) in Streptozotocin (STZ) induced diabetic rats and estimating its potential to ameliorate altered level of biochemical parameters, serum electrolytes level and haematological indices along with its effect on body weight of treated rats. The albino rats were selected to observe oral glucose tolerance test by oral intake of aq. glucose solution (4g/kg, body weight) in normal rats and estimation of blood glucose level after administration of AEOBS at 250mg/kg, 500mg/kg and standard drug glibenclamide at 0...
November 12, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27843779/the-role-of-non-steroidal-anti-inflammatory-drugs-nsaids-in-the-treatment-of-patients-with-hepatic-disease-a-review-article
#5
REVIEW
Maryam Soleimanpour, Farnad Imani, Saeid Safari, Sarvin Sanaie, Hassan Soleimanpour, Hoorolnesa Ameli, Seyed Moayed Alavian
CONTEXT: Patients with hepatic dysfunction suffer from many problems and associated complications in organs other than the liver. Therefore, it is very important to investigate the effects of different drugs in the treatment of these patients. Due to the high consumption of non-steroidal anti-inflammatory drugs (NSAIDs), studying the effects of these drugs in patients with hepatic dysfunction is particularly important. EVIDENCE ACQUISITION: Research studies published from 1958 to 2014 were investigated in the present study...
August 2016: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/27842774/mechanisms-of-drug-induced-hepatotoxicity
#6
REVIEW
Amina Ibrahim Shehu, Xiaochao Ma, Raman Venkataramanan
Drug-induced hepatotoxicity (DIH) is a significant cause of acute liver failure and liver transplantation. Diagnosis is challenging due to the idiosyncratic nature, its presentation in the form of other liver disease, and the lack of a definite diagnostic criteria. Generation of reactive metabolites, oxidative stress, and mitochondrial dysfunction are common mechanisms involved in DIH. Certain risk factors associated with a drug and within an individual further predispose patients to DIH.
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27842769/drug-induced-acute-liver-failure
#7
REVIEW
Shahid Habib, Obaid S Shaikh
Drug-induced acute liver failure (ALF) disproportionately affects women and nonwhites. It is most frequently caused by antimicrobials and to a lesser extent by complementary and alternative medications, antiepileptics, antimetabolites, nonsteroidals, and statins. Most drug-induced liver injury ALF patients have hepatocellular injury pattern. Cerebral edema and intracranial hypertension are the most serious complications of ALF. Other complications include coagulopathy, sepsis, metabolic derangements, and renal, circulatory, and respiratory dysfunction...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27832041/investigation-of-liver-dysfunction-who-should-we-test-for-hepatitis-e
#8
Sebastian J Wallace, Glynn W Webb, Richie G Madden, Hugh C Dalton, Joanne Palmer, Richard T Dalton, Adam Pollard, Rhys Martin, Vasilis Panayi, Gwyn Bennett, Richard P Bendall, Harry R Dalton
AIM: Hepatitis E virus (HEV) is endemic in developed countries, but unrecognized infection is common. Many national guidelines now recommend HEV testing in patients with acute hepatitis irrespective of travel history. The biochemical definition of 'hepatitis' that best predicts HEV infection has not been established. This study aimed to determine parameters of liver biochemistry that should prompt testing for acute HEV. METHODS: This was a retrospective study of serial liver function tests (LFTs) in cases of acute HEV (n=74) and three comparator groups: common bile duct stones (CBD, n=87), drug-induced liver injury (DILI, n=69) and patients testing negative for HEV (n=530)...
November 9, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27825165/lignans-extracted-from-eucommia-ulmoides-oliv-protects-against-ages-induced-retinal-endothelial-cell-injury
#9
Ban Liu, Chao-Peng Li, Wen-Qi Wang, Shu-Guang Song, Xiu-Ming Liu
BACKGROUND/AIMS: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27800121/erectile-dysfunction-drugs-changed-the-protein-expressions-and-activities-of-drug-metabolising-enzymes-in-the-liver-of-male-rats
#10
Salah A Sheweita, Mona Wally, Mostafa Hassan
Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27783862/adipose-tissue-derived-plasminogen-activator-inhibitor-1-function-and-regulation
#11
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27782940/effects-of-obesity-and-leptin-deficiency-on-morphine-pharmacokinetics-in-a-mouse-model
#12
Nicholas M Dalesio, Craig W Hendrix, Douglas Hale McMichael, Carol B Thompson, Carlton K K Lee, Huy Pho, Rafael S Arias, Rachael Rzasa Lynn, Jeffrey Galinkin, Myron Yaster, Robert H Brown, Alan R Schwartz
BACKGROUND: Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. METHODS: Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy...
December 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27765658/occupational-exposures-at-a-polyvinyl-chloride-production-facility-are-associated-with-significant-changes-to-the-plasma-metabolome
#13
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27720992/an-antigen-encapsulating-nanoparticle-platform-for-th1-17-immune-tolerance-therapy
#14
Derrick P McCarthy, Jonathan Woon-Teck Yap, Christopher T Harp, W Kelsey Song, Jeane Chen, Ryan M Pearson, Stephen D Miller, Lonnie D Shea
Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE)...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27712010/hepatic-manifestations-of-inflammatory-bowel-diseases
#15
Sophie Restellini, Olivier Chazouillères, Jean-Louis Frossard
Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders, reported both in Crohn's disease (CD) and ulcerative colitis (UC). They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions. Fatty liver is considered as the most common hepatobiliary complication in IBD whilst primary sclerosing cholangitis (PSC) the most specific one. Less frequently, IBD-associated hepatobiliary disorders include: autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis (PBC), hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, and liver abscess...
October 6, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27703513/clinical-characteristics-of-drug-induced-liver-injury-and-related-risk-factors
#16
Ren-Jie Lu, Yan Zhang, Feng-Lei Tang, Zhong-Wei Zheng, Zheng-Da Fan, Shan-Mei Zhu, Xian-Feng Qian, Na-Na Liu
Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory-specific serological markers. In this study, we comprehensively assessed the clinical characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes concerning DILI, and explored the similarities in mechanisms between Chinese and Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for systematic retrospective study...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27665770/usefulness-of-in-vitro-combination-assays-of-mitochondrial-dysfunction-and-apoptosis-for-the-estimation-of-potential-risk-of-idiosyncratic-drug-induced-liver-injury
#17
Keisuke Goda, Tadakazu Takahashi, Akio Kobayashi, Toshiyuki Shoda, Hideyuki Kuno, Shoichiro Sugai
Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27665478/protective-and-curative-effects-of-bacillus-subtilis-spb1-biosurfactant-on-high-fat-high-fructose-diet-induced-hyperlipidemia-hypertriglyceridemia-and-deterioration-of-liver-function-in-rats
#18
Raida Zouari, Khaled Hamden, Abdelfattah El Feki, Khansa Chaabouni, Fatma Makni-Ayadi, Choumous Kallel, Fahima Sallemi, Semia Ellouze-Chaabouni, Dhouha Ghribi-Aydi
This study was aimed to assess the plausible anti-obesity effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant on high fat high fructose diet-fed rats (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet (CD), HFFD, HFFD supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD+Bios1, 10mg/kg/day), HFFD receiving standard drug (HFFD+Torva, 10mg/kg/day) or SPB1 biosurfactant (HFFD+Bios2, 10mg/kg/day) during the last 4 weeks of the study...
September 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27651591/study-of-abnormal-liver-function-test-during-pregnancy-in-a-tertiary-care-hospital-in-chhattisgarh
#19
Nalini Mishra, V N Mishra, Parineeta Thakur
INTRODUCTION: Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. MATERIAL AND METHOD: Eighty pregnant women with abnormal liver dysfunction were studied prospectively...
October 2016: Journal of Obstetrics and Gynaecology of India
https://www.readbyqxmd.com/read/27637870/-quetiapine-and-anticholinergic-drugs-induced-ischaemic-colitis-a-case-study
#20
P Cuny, M Houot, S Ginisty, S Horowicz, F Plassart, H Mentec, P Eftekhari
INTRODUCTION: The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects. CASE REPORT: A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction...
September 13, 2016: L'Encéphale
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