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Drug-induced hepatotoxicity

B Vincenzi, A Russo, A Terenzio, A Galvano, D Santini, F Vorini, R Antonelli-Incalzi, U Vespasiani-Gentilucci, G Tonini
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC)...
October 2018: Critical Reviews in Oncology/hematology
Fernando Bessone, Melisa Dirchwolf, María Agustina Rodil, María Valeria Razori, Marcelo G Roma
BACKGROUND: Nonalcoholic fatty disease (NAFLD) is the most common liver disease, since it is strongly associated with obesity and metabolic syndrome pandemics. NAFLD may affect drug disposal and has common pathophysiological mechanisms with drug-induced liver injury (DILI); this may predispose to hepatoxicity induced by certain drugs that share these pathophysiological mechanisms. In addition, drugs may trigger fatty liver and inflammation per se by mimicking NAFLD pathophysiological mechanisms...
September 7, 2018: Alimentary Pharmacology & Therapeutics
Shweta Pandey, Vijay Kumar, Ankita Leekha, Nishant Rai, Farhan Jalees Ahmad, Anita Kamra Verma, Sushama Talegaonkar
PURPOSE: The present investigation was aimed at developing Teriflunomide (TEF) and Methotrexate (MTX) loaded hydroxyapatite nanoparticles and increasing tolerability towards combination therapy against rheumatoid arthritis by reducing hepatotoxicity. METHODS: Drug-loaded HAp-NPs were synthesized by wet-chemical precipitation method and optimized by Box-Behnken experimental design. The developed NPs were subjected to in vitro and in vivo characterization. In-vivo pharmacodynamics and biochemical studies were performed on adjuvant- induced arthritis model treated with different formulations; MTX-TEF-SOL, TEF-HAp-NP, MTX-HAp-NP, TEF-MTX-HAp-NP, FOLITRAX-10 and AUBAGIO...
September 5, 2018: Pharmaceutical Research
Weijia Han, Qiao Wu, Xiaohui Zhang, Zhongping Duan
Many categories of drugs can induce hepatotoxicity, so improving the prediction of toxic drugs is important. In vitro models using human hepatocytes are more accurate than in vivo animal models. Good in vitro models require an abundance of metabolic enzyme activities and normal cellular polarity. However, none of the in vitro models can completely simulate hepatocytes in the human body. There are two ways to overcome this limitation: enhancing the metabolic function of hepatocytes and changing the cultural environment...
September 5, 2018: Journal of Applied Toxicology: JAT
Humberto de Moura Barbosa, Dionísio Amaral, Jailson Nunes do Nascimento, Dijanah Cota Machado, Thiago Antônio de Sousa Araújo, Ulysses Paulino de Albuquerque, Jackson Roberto Guedes da Silva Almeida, Larissa Araújo Rolim, Norberto Peporine Lopes, Dayane Aparecida Gomes, Eduardo Carvalho Lira
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM) is one of the most important medical emergencies of the 21st century. However, commercially available oral drugs with antidiabetic properties have been limited because of potential side effects, such as: hypoglycemia, weight gain, hepatic dysfunction and abdominal discomfort. As well as antidiabetic drugs, many types of medicinal herbal supplements are utilized as alternative treatments for DM and related comorbidities. Spondias tuberosa Arruda (Anacardiaceae), popularly known as "umbu", has been used in traditional medicine to treat a vast range of diseases, including DM, infections, digestive disorders, diarrhea and menstrual abnormalities...
September 1, 2018: Journal of Ethnopharmacology
Amani S Awaad, Ahmed M Alafeefy, Fatmah A S Alasmary, Reham M El-Meligy, Saleh I Alqasoumi
The Novel target compounds (CP-1-7) were synthesized and tested at doses up to 1000 mg/kg for their entitled activities. They exerted promising results without any behavioral changes and mortality in mice. Therefore, according to the results obtained in our study, it could be categorized as highly safe agents for treating UC since substances possessing LD50 higher than 50 mg/kg are considered nontoxic. They also possessed a potent anti-ulcerogenic activity with different potentials. The most effective compound was CP-4, it produced 97...
December 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Chunmin Li, Yanan Ming, Zhengyang Wang, Qingling Xu, Lvfeng Yao, Dongke Xu, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao
As an analgesic and antipyretic drug, acetaminophen (APAP) is commonly used and known to be safe at therapeutic doses. In many countries, the overuse of APAP provokes acute liver injury and even liver failure. APAP-induced liver injury (AILI) is the most used experimental model of drug-induced liver injury (DILI). Here, we have demonstrated elevated levels of growth arrest and DNA damage-inducible 45α (GADD45α) in the livers of patients with DILI/AILI, in APAP-injured mouse livers and in APAP-treated hepatocytes...
August 27, 2018: Cellular and Molecular Life Sciences: CMLS
Hanvit Cha, Seoyoon Lee, Jin Hyup Lee, Jeen-Woo Park
Acetaminophen (N-acetyl-p-aminophenol, AAP) is an effective analgesic and antipyretic drug with minimal toxicity when used at therapeutic doses. However, AAP overdose is the most common cause of drug-induced acute liver failure and one of the main causes of morbidity and mortality. p-Coumaric acid (PCA) is the most abundant isomer of hydroxycinnamic acid in nature, and it can be widely found in fruits, vegetables, and plants products. PCA has strong antioxidant activity and exhibits protective effects in numerous disease models associated with reactive oxygen species (ROS) generation...
August 24, 2018: Food and Chemical Toxicology
Akshay Sharma, Elisa Akagi, Aji Njie, Sachin Goyal, Camelia Arsene, Geetha Krishnamoorthy, Murray Ehrinpreis
The Drug Induced Liver Injury Network reports dietary supplements as one of the most important causes of drug induced hepatotoxicity, yet millions of people use these supplements without being aware of their potential life-threatening side effects. Garcinia cambogia (GC) extract is an herbal weight loss supplement, reported to cause fulminant hepatic failure. We present a case of a 57-year-old female with no previous history of liver disease, who presented with acute hepatitis due to GC extract taken for weight loss, which resolved after stopping it and got reaggravated on retaking it...
2018: Case Reports in Gastrointestinal Medicine
Xiao-Li Li, Xiao-Chang Liu, Yu-Lin Song, Ru-Tao Hong, Hai Shi
BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points...
August 24, 2018: BMC Gastroenterology
Robert John Fontana, Elizabeth Theresa Cirulli, Jiezhun Gu, David Kleiner, David Ostrov, Elizabeth Phillips, Ryan Schutte, Huiman Barnhart, Naga Chalasani, Paul Brent Watkins, Jay H Hoofnagle
BACKGROUND & AIMS: Terbinafine is an antifungal agent that has been associated with rare instances of hepatotoxicity. In this study we aimed to describe the presenting features and outcomes of patients with terbinafine hepatotoxicity and to investigate the role of human leukocyte antigen (HLA)-A*33:01. METHODS: Consecutive high causality cases of terbinafine hepatotoxicity enrolled into the Drug Induced Liver Injury Network were reviewed. DNA samples underwent high-resolution confirmatory HLA sequencing using the Ilumina MiSeq platform...
August 21, 2018: Journal of Hepatology
Zhi-Qiang Cheng, Jia-Li Song, Kongkai Zhu, Juan Zhang, Cheng-Shi Jiang, Hua Zhang
A marine natural product, pulmonarin B ( 1 ), and a series of related tacrine hybrid analogues were synthesized and evaluated as cholinesterase (ChE) inhibitors. The in vitro ChE assay results revealed that 1 showed moderate dual acetylcholinesterase (AChE)/ butyrylcholinesterase (BChE) inhibitory activity, while the hybrid 12j proved to be the most potent dual inhibitor among the designed derivatives, being almost as active as tacrine. Molecular modeling studies together with kinetic analysis suggested that 12j interacted with both the catalytic active site and peripheral anionic site of AChE...
August 21, 2018: Marine Drugs
Carlota Oleaga, Anne Riu, Sandra Rothemund, Andrea Lavado, Christopher W McAleer, Christopher J Long, Keisha Persaud, Narasimhan Sriram Narasimhan, My Tran, Jeffry Roles, Carlos A Carmona-Moran, Trevor Sasserath, Daniel H Elbrecht, Lee Kumanchik, L Richard Bridges, Candace Martin, Mark T Schnepper, Gail Ekman, Max Jackson, Ying I Wang, Reine Note, Jessica Langer, Silvia Teissier, James J Hickman
Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function...
November 2018: Biomaterials
Christopher D Jackson, Michael J Clanahan, Kiran Joglekar, Sorawit T Decha-Umphai
A drug-induced liver injury is one of the most common causes of acute liver failure. While acetaminophen is the most common etiology, other offending medications include amoxicillin-clavulanic acid, amiodarone, isoniazid, and fluoroquinolones to name a few. Gabapentin, a gamma-aminobutyric acid (GABA) analogue, has infrequently been reported to cause liver injury; however, the causality in the previous reports is contested. Herein, we report a gabapentin-induced hepatocellular injury in a patient without another identifiable cause for acute liver injury...
March 4, 2018: Curēus
Ilioara Oniga, Cristina Pușcaș, Radu Silaghi-Dumitrescu, Neli-Kinga Olah, Bogdan Sevastre, Raluca Marica, Ioan Marcus, Alexandra Cristina Sevastre-Berghian, Daniela Benedec, Carmen Elena Pop, Daniela Hanganu
The biological properties and main phenolic compounds of the O. vulgare L. ssp. vulgare extract are described in the present paper. The polyphenolic compounds were analyzed by chromatographic and spectrophotometric techniques. The antioxidant potential was evaluated using several methods: CUPRAC (cupric ion reducing antioxidant capacity), FRAP (ferric reducing ability of plasma), inhibition of lipid peroxidation catalyzed by cytochrome c, and superoxide (SO) scavenging assays. The antimicrobial activity of the oregano extract was evaluated by means of agar-well diffusion assay...
August 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yuanqiang Wang, Weiwei Lin, Nan Wu, Xibing He, Junmei Wang, Zhiwei Feng, Xiang-Qun Xie
Paracetamol is a relatively safe analgesia/antipyretic drug without the risks of addiction, dependence, tolerance, and withdrawal when used alone. However, when administrated in an opioid/paracetamol combination product, which often contains a large quantity of paracetamol, it can be potentially dangerous due to the risk of hepatotoxicity. Paracetamol is known to be metabolized into N-(4-hydroxyphenyl)-arachidonamide (AM404) via fatty acid amide hydrolase (FAAH) and into N-acetyl-p-benzoquinone imine (NAPQI) via cytochrome P450 (CYP) enzymes...
August 18, 2018: Journal of Molecular Modeling
Omnyah A El-Kharashi, Dalia Alaa El-Din Aly El-Waseef, Enas S Nabih, Doaa I Mohamed
BACKGROUND: NLRP3 inflammasome is described in many pathological conditions and is also involved in drug induced liver injury. AIM OF THE WORK: To investigate the role of NLRP3 inflammasome in liver injury induced by chronic alcohol and/or atorvastatin ingestion. MATERIALS AND METHODS: Sixty male Wistar rats were used. They were divided into 5 groups: (I) control naïve (II) Alcoholic: given ethanol 8 g/kg/day, p.o (III) Atorvastatin: given atorvastatin 10 mg/kg/day, p...
August 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nicole Kapral, Rovin Saxena, Anupam Ashutosh Sule, Brian Markle
Nitrofurantoin remains the gold standard treatment of uncomplicated cystitis as well as prophylactic treatment of recurrent urinary tract infections. Drug-induced hepatotoxicity presents in acute (3 in 1 000 000) and chronic (1 in 1500) forms. We present a patient with acute liver failure after 5 days of treatment. A 69-year-old man admitted for chronic obstructive pulmonary disease exacerbation 5 days into treatment for cystitis with nitrofurantoin. On admission he was noted to be jaundiced with elevated liver enzymes and normal international normalised ratio...
August 16, 2018: BMJ Case Reports
Jorge Soares, João Vasco Santos, António Sarmento, Altamiro Costa-Pereira
BACKGROUND/AIMS: Spontaneous viral clearance of the chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-infected patients is a rare event. We aimed to identify the clinical, therapeutic, demographic, and laboratory features associated with spontaneous HCV clearance in 16 HIV-infected patients with chronic hepatitis C (CHC, the largest case series, to our knowledge). METHODS: This case series study reports the findings from 16 HIV/HCV coinfected patients with CHC who experienced spontaneous clearance of HCV infection...
August 16, 2018: Intervirology
Michele S Barnhill, Mark Real, James H Lewis
Drug-induced liver injury (DILI) remains an increasingly recognized cause of hepatotoxicity and liver failure worldwide. In 2017, we continued to learn about predicting, diagnosing, and prognosticating drug hepatotoxicity. Areas covered: In this review, we selected from over 1200 articles from 2017 to synopsize updates in DILI. There were new HLA haplotypes associated with medications including HLA-C0401 and HLA-B*14. There has been continued work with quantitative systems pharmacology, particularly with the DILIsym® initiative, which employs mathematical representations of DILI mechanisms to predict hepatotoxicity in simulated populations...
September 3, 2018: Expert Review of Gastroenterology & Hepatology
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