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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/28100990/drug-induced-liver-injury-associated-with-complementary-and-alternative-medicines
#1
Koji Takahashi, Tatsuo Kanda, Shin Yasui, Yuki Haga, Junichiro Kumagai, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Masato Nakamura, Makoto Arai, Osamu Yokosuka
A 24-year-old man was admitted due to acute hepatitis with unknown etiology. After his condition and laboratory data gradually improved with conservative therapy, he was discharged 1 month later. Two months after his discharge, however, liver dysfunction reappeared. After his mother accidentally revealed that he took complementary and alternative medicine, discontinuation of the therapy caused his condition to improve. Finally, he was diagnosed with a recurrent drug-induced liver injury associated with Japanese complementary and alternative medicine...
September 2016: Case Reports in Gastroenterology
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/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#3
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28024294/celecoxib-administration-reduced-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-injury-in-septic-rats
#4
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP)...
December 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28000142/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-with-teicoplanin-a-case-report
#5
Sholeh Ebrahimpour, Mehdi Mohammadi, Kheirollah Gholami
Intramuscular teicoplanin (400 mg every 12 h for three doses, then 400 mg daily, intramuscularly) was prescribed for a 37-year-old woman with presumptive diagnosis of cellulitis. On the 14th day of treatment, she developed generalized maculopapular rash, accompanied by fever, wheezing, shortening of breath, and lymphadenopathy. Lab tests revealed abnormal liver enzymes, leukocytosis, and eosinophilia. The treatment was interrupted with suspicion of drug reaction. Fever subsided after 48 h. Skin eruption and respiratory symptoms began to resolve within 2 weeks...
December 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27995280/dietary-fructose-as-a-risk-factor-for-non-alcoholic-fatty-liver-disease-nafld
#6
REVIEW
Salamah Mohammad Alwahsh, Rolf Gebhardt
Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD...
December 19, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27993716/the-fxr-agonist-px20606-ameliorates-portal-hypertension-by-targeting-vascular-remodelling-and-sinusoidal-dysfunction
#7
Philipp Schwabl, Eva Hambruch, Berit A Seeland, Hubert Hayden, Michael Wagner, Lukas Garnys, Bastian Strobel, Tim-Lukas Schubert, Florian Riedl, Dieter Mittereger, Michael Burnet, Patrick Starlinger, Georg Oberhuber, Ulrich Deuschle, Nataliya Rohr-Udilova, Bruno K Podesser, Markus Peck-Radosavljevic, Thomas Reiberger, Claus Kremoser, Michael Trauner
BACKGROUND & AIMS: Steroidal FXR agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. METHODS: In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7 days) and cirrhotic (carbon-tetrachloride, CCl4, 14 weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged...
December 16, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#8
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, P Darwin 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...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890005/mechanism-based-inhibitors-from-phytomedicine-risks-of-hepatotoxicity-and-their-potential-hepatotoxic-substructures
#9
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
#10
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
#11
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...
December 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
#12
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
#13
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
#14
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
#15
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)...
February 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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