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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#1
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28302559/in-vitro-monoamine-oxidase-inhibition-potential-of-alpha-methyltryptamine-analog-new-psychoactive-substances-for-assessing-possible-toxic-risks
#2
Lea Wagmann, Simon D Brandt, Pierce V Kavanagh, Hans H Maurer, Markus R Meyer
Tryptamines have emerged as new psychoactive substances (NPS), which are distributed and consumed recreationally without preclinical studies or safety tests. Within the alpha-methylated tryptamines, some of the psychoactive effects of the prototypical alpha-methyltryptamine (AMT) have been described decades ago and a contributing factor of its acute toxicity appears to involve the inhibition of monoamine oxidase (MAO). However, detailed information about analogs is scarce. Therefore, thirteen AMT analogs were investigated for their potential to inhibit MAO...
March 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28292009/selenium-and-a-newly-synthesized-thiocyanoacetamide-reduce-doxorubicin-gonadotoxicity-in-male-rat
#3
Marwa Boussada, Ridha Ben Ali, Azaa Ben Said, Khouloud Bokri, Azaiez Ben Akacha, Chedli Dziri, Michèle Véronique El May
Despite its deleterious effect on healthy cells and highly regenerating cells such as spermatozoa, Doxorubicin (DOX) is still one of the most used anticancer drugs in the last decades. The present work aimed to investigate the ability of the selenium (Se) and the thiocyanoacetamide (T) to reduce DOX toxicity in gonad. Adult male rats were treated with DOX intravenously (i.v.) at 3.7mg/kg/week associated with Se intragastrically (i.g.) at 0.2mg/kg/day or with T at 10mg/kg/day i.g. After 47days of treatment, sperm quality, biochemical parameters, blood cell count and histological changes in liver, testis and epididymis were assessed...
March 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28291796/the-effect-of-acetaminophen-on-ubiquitin-homeostasis-in-saccharomyces-cerevisiae
#4
Angelina Huseinovic, Jolanda S van Leeuwen, Tibor van Welsem, Iris Stulemeijer, Fred van Leeuwen, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28291734/safety-assessment-of-the-aqueous-extract-of-the-flowers-of-nymphaea-lotus-linn-nymphaeaceae-acute-neuro-and-subchronic-oral-toxicity-studies-in-albinos-wistar-rats
#5
Mireille Kameni Poumeni, Danielle Claude Bilanda, Paul Désiré Dzeufiet Djomeni, Yolande Sandrine Mengue Ngadena, Marguerite Francine Mballa, Madeleine Chantal Ngoungoure, Agnès Carolle Ouafo, Théophile Dimo, Pierre Kamtchouing
BACKGROUND: Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system...
March 14, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28289388/hla-b-57-allele-is-associated-with-concomitant-anti-tuberculosis-and-antiretroviral-drugs-induced-liver-toxicity-in-ethiopians
#6
Zelalem Petros, Junko Kishikawa, Eyasu Makonnen, Getnet Yimer, Abiy Habtewold, Eleni Aklillu
Drug-induced liver injury (DILI) is a known adverse effect of both anti-tuberculosis (anti-TB) and antiretroviral (ARV) drugs. Recent studies highlight the implications of genetic predispositions to DILI. We performed a case-control study to identify Human Leukocyte Antigen-B (HLA-B) variant alleles associated with anti-TB and ARV co-treatment induced liver toxicity in Ethiopian TB and HIV co-infected patients. A total of 495 newly diagnosed TB and HIV co-infected patients were enrolled and received rifampicin based anti-TB and efavirenz based ARV therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28288894/endogenous-inspired-biomineral-installed-hyaluronan-nanoparticles-as-ph-responsive-carrier-of-methotrexate-for-rheumatoid-arthritis
#7
Md Mahmudul Alam, Hwa Seung Han, Shijin Sung, Jin Hee Kang, Keum Hee Sa, Hasan Al Faruque, Jungwan Hong, Eon Jeong Nam, In San Kim, Jae Hyung Park, Young Mo Kang
Methotrexate (MTX), an anchor drug for rheumatoid arthritis (RA), has been suffered from refractoriness and high toxicity limiting effective dosage. To mitigate these challenges, the ability to selectively deliver MTX to arthritis tissue is a much sought-after modality for the treatment of RA. In this study, we prepared mineralized nanoparticles (MP-HANPs), composed of PEGylated hyaluronic acid (P-HA) as the hydrophilic shell, 5β-cholanic acid as the hydrophobic core, and calcium phosphate (CaP) as the pH-responsive mineral...
March 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#8
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28285327/biochemical-properties-and-vaccine-effect-of-recombinant-tpx-3-from-schistosoma-japonicum
#9
Yanhui Han, Bin Zhao, Min Zhang, Yang Hong, Hongxiao Han, Xiaodan Cao, Ke Lu, Jiaojiao Lin, Zhiqiang Fu
Thioredoxin peroxidases (TPxs) play an important role in maintaining redox homeostasis and in protecting organisms from the accumulation of toxic reactive oxygen species (ROS). In this study, we isolated the thioredoxin peroxidase-3 gene of Schistosoma japonicum, SjTPx-3. The open reading frame (ORF) of SjTPx-3 was 663 bp encoding 220 amino acids with a molecular weight of 24.99 kDa and an isoelectric point of 6.20. Quantitative real-time reverse transcription-polymerase chain reaction indicated that SjTPx-3 was expressed in all different stages of the parasites, with highest expression in 35-day-old worms...
March 11, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#10
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28276763/coumarins-from-the-bark-of-juglans-mandshurica-exhibited-anti-hepatoma-activities-via-inducing-apoptosis
#11
Guo-Dong Yao, Zhuo-Yang Cheng, Xin-Yue Shang, Pin-Yi Gao, Xiao-Xiao Huang, Shao-Jiang Song
Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract...
February 19, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28270644/protective-effect-of-quercetin-against-oxidative-stress-induced-toxicity-associated-with-doxorubicin-and-cyclophosphamide-in-rat-kidney-and-liver-tissue
#12
Sayad Kocahan, Zumrut Dogan, Erman Erdemli, Eylem Taskin
INTRODUCTION: Doxorubicin and cyclophosphamide are widely used anticancer drugs with substantial toxicity in noncancerous tissue resulting from oxidative damage. Quercetin is a potent antioxidant compound. We hypothesized that quercetin administration would ameliorate the toxic effects of doxorubicin and cyclophosphamide prior to pregnancy. MATERIALS AND METHODS: Cyclophosphamide, 27 mg/kg, and doxorubicin, 1.8 mg/kg, were administered to rats as intraperitoneal doses once every 3 weeks for a total of 10 weeks with or without concurrent treatment with quercetin, 10 mg/kg/d...
March 2017: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/28265001/phosphorylated-nuclear-receptor-car-forms-a-homodimer-to-repress-its-constitutive-activity-for-ligand-activation
#13
Ryota Shizu, Makoto Osabe, Lalith Perera, Rick Moore, Tatsuya Sueyoshi, Masahiko Negishi
Nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and disease development such as diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase PP2A dephosphorylates threonine 38 to activate CAR. Here we have demonstrated that CAR undergoes its homodimer-monomer conversion to regulate this dephosphorylation...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28263462/omics-for-understanding-the-gut-liver-microbiome-axis-and-precision-medicine
#14
Jag Khalsa, Linda C Duffy, Gabriela Riscuta, Pamela Starke-Reed, Van S Hubbard
Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28262508/the-role-of-ntcp-oatp2-bsep-and-mrp2-in-liver-injury-induced-by-dioscorea-bulbifera-l-and-diosbulbin-b-in-mice
#15
Xiao-Yu Qu, Li-Na Tao, Si-Xi Zhang, Jing-Meng Sun, Jun-Qi Niu, Yan-Hua Ding, Yan-Qing Song
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels...
February 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28257954/effects-of-tetrahydroberberine-and-tetrahydropalmatine-on-hepatic-cytochrome-p450-expression-and-their-toxicity-in-mice
#16
Dujun Wang, Kai Wang, Danjuan Sui, Zhen Ouyang, Haiyu Xu, Yuan Wei
The aim of this study was to investigate the effects of tetrahydroberberine (THB) and tetrahydropalmatine (THP) on the expression of mouse liver cytochrome P450s, and evaluate their liver toxicity in mice. Real-time polymerase chain reaction (PCR) and western blot analyses were used to analyze the expression of major P450 isoforms. Liver toxicity was evaluated by measuring serum biochemical parameters and performing histopathological analysis. The real-time PCR results showed that THB induced Cyp1a2 (1.66 ± 0...
February 28, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28257576/evaluation-of-dili-predictive-hypotheses-in-early-drug-development
#17
Rosa Chan, Leslie Z Benet
Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals. DILI has been shown to be dependent on both daily dose and extent of hepatic metabolism. Yet, early in drug development daily dose is unknown. Here, we perform a comprehensive analysis of the published hypotheses that attempt to predict DILI, including a new analysis of the Biopharmaceutics Drug Disposition Classification System (BDDCS) in evaluating the severity of DILI warnings in drug labels approved by the FDA and the withdrawal status due to adverse drug reactions (ADRs)...
March 15, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28253087/genome-wide-association-studies-for-idiosyncratic-drug-induced-hepatotoxicity-looking-back-looking-forward-to-next-generation-innovation
#18
Zelalem Petros, Eyasu Makonnen, Eleni Aklillu
Idiosyncratic drug-induced hepatotoxicity is a formidable challenge for rational drug discovery and development, as well as the science of personalized medicine. There is evidence that hereditary factors, in part, contribute to drug toxicity. This expert analysis and review offer the insights gained, and the challenges ahead, for genome-wide association studies (GWASs) of idiosyncratic drug-induced hepatotoxicity. Published articles on genome-wide and subsequent replication studies were systematically searched in the PubMed electronic database...
March 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28250689/amiodarone-induced-loculated-pleural-effusion-without-pulmonary-parenchymal-involvement-a-case-report-and-literature-review
#19
Amer Hawatmeh, Mohammad Thawabi, Ashraf Jmeian, Hamid Shaaban, Fayez Shamoon
Amiodarone is an extremely effective antiarrhythmic drug that is known to cause many adverse effects such as pulmonary, thyroid, and liver toxicities. Of these, pulmonary toxicity is most serious. Pulmonary toxicity can present as interstitial pneumonitis, organizing pneumonia, pulmonary nodules and masses, and very rarely pleural effusions. We present a case of a 73-year-old male who presented with progressive exertional dyspnea, nonproductive cough, generalized fatigue, and weakness. He was found to have multiorgan toxicity secondary to long-term treatment with high doses of amiodarone...
January 2017: Journal of Natural Science, Biology, and Medicine
https://www.readbyqxmd.com/read/28250317/strategic-drug-design-to-avoid-the-metabolic-activation-of-hepatotoxic-drugs
#20
Tomoyuki Ohe, Kyoko Takahashi, Shigeo Nakamura, Tadahiko Mashino
 Adverse reactions are one of the most important issues in drug development, as well as in the therapeutic usage of drugs during the post-approval stage. Specifically, idiosyncratic adverse drug reactions (IDR) occur in only a small group of patients who are treated with certain drugs, and are unpredictable. It is widely accepted that drug-induced IDR is often associated with CYP-mediated bioactivation. Benzbromarone (BBR) is effective in the treatment of hyperuricemia, and has been used as an effective drug in Japan for a long time...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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