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drug induced liver toxicity

Yi-Chia Su, Chih-Chien Wu
A 54-year-old woman presented at the emergency department after experiencing lower limb weakness and bilateral ankle pain for 2 days. She had a history of type 2 diabetes mellitus, diabetes mellitus nephropathy with chronic kidney disease, and chronic gouty arthritis. She had received 0.6 mg colchicine orally once or twice daily for 8 months. Four days prior to her emergency department visit, she was discharged from our nephrology ward, where she had been admitted because of a urinary tract infection. During hospitalization, she was treated with intravenous cefazolin for 7 days...
December 2015: Drug Saf Case Rep
Ryo Mitsugi, Kyohei Sumida, Yoshiko Fujie, Robert H Tukey, Tomoo Itoh, Ryoichi Fujiwara
Trovafloxacin is an antibiotic that was withdrawn from the market relatively soon after its release due to the risk of hepatotoxicity. Trovafloxacin is mainly metabolized to its acyl-glucuronide by uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) 1A1. In this study, we examined whether the acyl-glucuronide is involved in the development of hepatotoxicity. A UGT1A1-induced cell model was developed and the toxicity of trovafloxacin acyl-glucuronide was evaluated. The UGT1A1-induced cell model was developed by treating HepG2 cells with chrysin for 48 h...
2016: Biological & Pharmaceutical Bulletin
Hesbon Z Amenya, Chiharu Tohyama, Seiichiroh Ohsako
The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1)...
October 7, 2016: Scientific Reports
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
Seung-Young Oh, Hannah Lee, Yang-Hyo Park, Ho Geol Ryu
Seizure is the second most common neurologic complication after liver transplantation and may be caused by metabolic abnormalities, electrolyte imbalance, infection, and immunosuppressant toxicity. A 61-year-old male patient underwent liver transplantation due to hepatitis B virus-related liver cirrhosis with portal systemic encephalopathy. The immediate postoperative course of the patient was uncomplicated. However, on postoperative day (POD) 6, weakness developed in both lower extremities. No abnormal findings were detected on a brain computed tomography (CT) scan on POD 8, but a generalized tonic clonic seizure developed which was difficult to control even with multiple antiepileptic drugs...
October 2016: Korean Journal of Anesthesiology
Kavisa Ghosh, N Indra, G Jagadeesan
BACKGROUND: Isoniazid, also called isonicotinyl hydrazine (INH), is a commonly used drug for treating tuberculosis. The main drawback is its toxic side effects. Centella asiatica has long been used in the Ayurvedic system of medicine owing to its wide medicinal properties. This study was designed to examine the effectiveness of C. asiatica ethanolic leaf extract (CA) on INH-treated albino rats. METHODS: The adverse effects induced by INH (50 mg/kg bw) administration on haematological parameters, oxidative status (thiobarbituric acid-reactive substances, superoxide dismutase, catalase, and reduced glutathione), liver and kidney function markers, and their amelioration by various concentrations of CA (20, 40, 60, and 100 mg/kg bw) or silymarin (SIL) (50 mg/kg bw, administered before 1 h of INH treatment for 30 days to rats) were studied...
October 4, 2016: Journal of Basic and Clinical Physiology and Pharmacology
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: Your report will be published anonymously unless otherwise requested...
September 2016: Hospital Pharmacy
Ana Vanessa Nascimento, Amit Singh, Hassan Bousbaa, Domingos Ferreira, Bruno Sarmento, Mansoor M Amiji
: Efficiency of chemotherapy is often limited by low therapeutic index of the drug as well as emergence of inherent and acquired drug resistance in cancer cells. As a common strategy to overcome drug resistance, higher doses of chemo-agents are administered. However, adverse side effects are usually increased as a consequence. A potentially effective approach is to combine chemotherapy with other therapeutic strategies such as small interfering RNAs (siRNAs) that allow the use of lower yet efficient doses of the anticancer drugs...
September 30, 2016: Acta Biomaterialia
Bogdan Silviu Ungureanu, Cristian-Mihail Teodorescu, Adrian Săftoiu
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results. In principle, three different approaches can be used in the treatment of tumors with superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia, drug targeting and selective suppression of tumor growth. This review focuses on the use of iron oxide nanoparticles for the diagnosis and treatment of liver cancer and offers a walkthrough from the MNPs imaging applicability to further therapeutic options, including their potential flaws...
September 2016: Journal of Gastrointestinal and Liver Diseases: JGLD
Franck A Atienzar, Eric A Blomme, Minjun Chen, Philip Hewitt, J Gerry Kenna, Gilles Labbe, Frederic Moulin, Francois Pognan, Adrian B Roth, Laura Suter-Dick, Okechukwu Ukairo, Richard J Weaver, Yvonne Will, Donna M Dambach
Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions...
2016: BioMed Research International
Robin Paudel, Prerna Dogra, Saurav Suman, Saurav Acharya, Jyoti Matta
Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80...
2016: Case Reports in Critical Care
Shingo Oda, Yuji Shirai, Sho Akai, Akira Nakajima, Koichi Tsuneyama, Tsuyoshi Yokoi
The acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs are potentially chemically reactive and are suggested to be implicated in toxicity, including hepatotoxicity, nephrotoxicity and drug hypersensitivity reactions. However, it remains unknown whether AG formation is related to toxicity in vivo. In this study, we sought to determine whether AG is involved in the pathogenesis of liver injury using a mouse model of diclofenac (DIC)-induced liver injury. Mice that were administered DIC alone exhibited significantly increased plasma alanine aminotransferase levels, whereas mice that were pretreated with the UDP-glucuronosyltransferase inhibitor (-)-borneol (BOR) exhibited suppressed alanine aminotransferase levels at 3 and 6 h after DIC administration although not significant at 12 h...
September 27, 2016: Journal of Applied Toxicology: JAT
Zelalem Petros, Ming-Ta Michael Lee, Atsushi Takahashi, Yanfei Zhang, Getnet Yimer, Abiy Habtewold, Wondwossen Amogne, Getachew Aderaye, Ina Schuppe-Koistinen, Taisei Mushiroda, Eyasu Makonnen, Michiaki Kubo, Eleni Aklillu
BACKGROUND: Drug-induced liver injury (DILI) is a well-recognized adverse event of anti tuberculosis drugs (ATD) possibly associated with genetic variations. The objective of this study was to perform genome-wide association study (GWAS) to identify genetic variants associated with the risk for ATD induced liver toxicity in Ethiopian patients. RESULT: Treatment-naïve newly diagnosed tuberculosis patients (n = 646) were enrolled prospectively and treated with rifampicin based short course anti-tuberculosis therapy...
September 26, 2016: BMC Genomics
Volker M Lauschke, Delilah F G Hendriks, Catherine C Bell, Tommy B Andersson, Magnus Ingelman-Sundberg
The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity...
September 23, 2016: Chemical Research in Toxicology
Jerine Peter Simon, Sabina Evan Prince
The liver is an important organ of the body, which has a vital role in metabolic functions. The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs...
September 22, 2016: Journal of Applied Toxicology: JAT
A Najibi, R Heidari, J Zarifi, A Jamshidzadeh, N Firoozabadi, H Niknahad
Background: Trazodone is an antidepressant agent widely administered for the treatment of depressive disorders. On the other hand, several cases of hepatic injury have been reported after Trazodone administration. Although the precise mechanism(s) of trazodone-induced liver injury is not known, some investigations proposed the role of reactive intermediates in this complication. This study was designed to investigate the role of reactive metabolites in hepatocytes injury induced by trazodone. Methods: Isolated rat hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein...
September 19, 2016: Drug Research
Said Said Elshama, Ayman El-Meghawry El-Kenawy, Hosam-Eldin Hussein Osman
OBJECTIVES: Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects. This study investigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder...
July 2016: Iranian Journal of Basic Medical Sciences
Gaurav Gupta, Kevin J Peine, Dalia Abdelhamid, Heidi Snider, Andrew B Shelton, Latha Rao, Sainath R Kotha, Andrew C Huntsman, Sanjay Varikuti, Steve Oghumu, C Benjamin Naman, Li Pan, Narasimham L Parinandi, Tracy L Papenfuss, A Douglas Kinghorn, Eric M Bachelder, Kristy M Ainslie, James R Fuchs, Abhay R Satoskar
Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a global health problem affecting millions of people worldwide. Treatment of VL largely depends on therapeutic drugs such as pentavalent antimonials, amphotericin B, and others, which have major drawbacks due to drug resistance, toxicity, and high cost. In this study, for the first time, we have successfully demonstrated the synthesis and antileishmanial activity of the novel sterol pentalinonsterol (PEN), which occurs naturally in the root of a Mexican medicinal plant, Pentalinon andrieuxii...
October 9, 2015: ACS Infectious Diseases
Charles D Magee, Stephen Witte, Ryan M Kwok, Patricia A Deuster
BACKGROUND: Supplement adulteration with anabolic-androgenic steroids (AAS) has been reported and AAS-associated drug-induced liver injury is clinically variable. OBJECTIVES: We present two cases of AAS-associated drug-induced liver injury in deployed service members, including the first report of clinical hepatotoxicity with desoxymethyltestosterone. We highlight variable hepatotoxicity patterns of AAS, raise concern with inaccurate supplement labeling and identify educational resources...
September 2016: Military Medicine
Tyler B Hughes, Na Le Dang, Grover P Miller, S Joshua Swamidass
Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs...
August 24, 2016: ACS Central Science
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