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https://www.readbyqxmd.com/read/28101470/protective-roles-of-n-acetyl-cysteine-and-or-taurine-against-sumatriptan-induced-hepatotoxicity
#1
Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal
Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101469/concurrent-inflammation-augments-antimalarial-drugs-induced-liver-injury-in-rats
#2
Hossein Niknahad, Reza Heidari, Roya Firuzi, Farzaneh Abazari, Maral Ramezani, Negar Azarpira, Massood Hosseinzadeh, Asma Najibi, Arastoo Saeedi
Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered. Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion)...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#3
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28088791/sinomenine-hydrochloride-inhibits-breast-cancer-metastasis-by-attenuating-inflammation-related-epithelial-mesenchymal-transition-and-cancer-stemness
#4
Xiao Li, Pingping Li, Chao Liu, Yu Ren, Xiaojiang Tang, Ke Wang, Jianjun He
Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#5
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28088257/clinical-and-experimental-research-in-antituberculosis-drug-induced-hepatotoxicity-a-review
#6
REVIEW
Udhaya Lavinya Baskaran, Evan Prince Sabina
Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity, its underlying mechanisms and alternative therapies for the same...
January 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#7
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/28073113/in-vitro-to-in-vivo-extrapolation-for-drug-induced-liver-injury-using-a-pair-ranking-method
#8
Zhichao Liu, Hong Fang, Jürgen Borlak, Ruth Roberts, Weida Tong
Preclinical animal toxicity studies may not accurately predict human toxicity. In light of this, in vitro systems have been developed that have the potential to supplement or even replace animal use. We examined in vitro to in vivo extrapolation (IVIVE) of gene expression data obtained from The Open Japanese Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) for 131 compounds given to rats for 28 days, and to human or rat hepatocytes for 24 hours. Notably, a Pair Ranking (PRank) method was developed to assess IVIVE potential with a PRank score based on the preservation of the order of similarity rankings of compound pairs between the platforms using a receiver operating characteristic (ROC) curve analysis to measure area under the curve (AUC)...
January 11, 2017: ALTEX
https://www.readbyqxmd.com/read/28070111/a-monkey-model-of-acetaminophen-induced-hepatotoxicity-phenotypic-similarity-to-human
#9
Satoshi Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, Hitomi Shimoda, Wataru Takasaki, Kazuhiko Mori
Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069506/one-step-fabrication-of-hydrogel-microcapsules-with-hollow-core-for-assembly-and-cultivation-of-hepatocyte-spheroids
#10
Christian Siltanen, Michaela Diakataou, Jeremy Lowen, Amranul Haque, Ali Rahimian, Gulnaz Stybayeva, Alexander Revzin
: 3D hepatic microtissues can serve as valuable liver analogues for cell-based therapies and for hepatotoxicity screening during preclinical drug development. However, hepatocytes rapidly dedifferentiate in vitro, and typically require 3D cultures systems or co-cultures for phenotype rescue. In this work we present a novel microencapsulation strategy, utilizing coaxial flow-focusing droplet microfluidics to fabricate microcapsules with liquid core and poly(ethylene glycol) (PEG) shell...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28068634/virgin-coconut-oil-supplementation-attenuates-acute-chemotherapy-hepatotoxicity-induced-by-anticancer-drug-methotrexate-via-inhibition-of-oxidative-stress-in-rats
#11
Ademola C Famurewa, Odomero G Ufebe, Chima A Egedigwe, Onyebuchi E Nwankwo, Godwin S Obaje
BACKGROUND: The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. METHODS: Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28066854/live-donor-liver-transplantation-for-antitubercular-drug-induced-acute-liver-failure
#12
Akshay P Bavikatte, S Sudhindran, Puneet Dhar, O V Sudheer, G Unnikrishnan, Dinesh Balakrishnan, Ramachandran N Menon
Antitubercular therapy (ATT)-induced hepatotoxicity is often over looked and active tuberculosis is considered a contraindication for liver transplantation, however it might be the only lifesaving option to certain patients of acute liver failure (ALF) due to ATT. We have assessed the outcome of live donor liver transplantation in ATT-induced ALF. A retrospective analysis of all the cases of ALF that underwent liver transplantation from 2006 to 2014 at the Amrita Institute of Medical Sciences was done. A total of seven (7...
January 9, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28063906/pyrazinamide-induced-hepatotoxicity-is-alleviated-by-4-pba-via-inhibition-of-the-perk-eif2%C3%AE-atf4-chop-pathway
#13
Hong-Li Guo, Hozeifa M Hassan, Ping-Ping Ding, Shao-Jie Wang, Xi Chen, Tao Wang, Li-Xin Sun, Lu-Yong Zhang, Zhen-Zhou Jiang
Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. In this study, we describe the role of ER stress in PZA induced hepatotoxicity in vivo and in vitro. We found that PZA induces apoptosis in HepG2 cells, and causes liver damage in rats, characterized by increased serum ALT, AST and TBA levels...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28063643/protective-effect-of-tritone-livosone-on-oxidative-dna-damage-and-its-hepatoprotective-potential-against-various-hepatotoxic-agent-in-wistar-rats
#14
Sheetal Kashinath Medhekar, Tejas Pandurang Jadhav, Vishal Sadashiv Sasane, Vikas Suresh Shende, Nagesh Hanmantrao Aloorkar, Anjali Baburao Chincholkar, Girish Sudhakar Soman, Ajit Shankarrao Kulkarni
AIM: To evaluate antioxidant activity, DNA damage inhibition and hepatoprotecitve potential of polyherbal formulation Tritone (Livosone). METHODS: In vitro antioxidant activity of Tritone formulation was performed by using DPPH assay. Hepatoprotecitve potential of Tritone was evaluated against various hepatotoxic agents including Paracetamol (2g/kg b. wt p.o. single dose on 15th day), Galactosamine (400mg/kg b. wt. i.p. single dose on 8th day) and Alcohol (30% p...
January 4, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28063021/hepatotoxicity-with-vismodegib-an-md-anderson-cancer-center-and-research-on-adverse-drug-events-and-reports-project
#15
Beatrice J Edwards, Dennis W Raisch, Smita S Saraykar, Ming Sun, Josh A Hammel, Hai T Tran, Nathaniel Wehr, Rasha Arabyat, Dennis P West
BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge(®), Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others...
January 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28060046/serious-adverse-reactions-from-anti-tuberculosis-drugs-among-599-children-hospitalized-for-tuberculosis
#16
Yiyuan Li, Yu Zhu, Qin Zhong, Xiaojun Zhang, Min Shu, Chaomin Wan
BACKGROUNDS: The purpose of the study was to summarize the clinical characteristics of serious adverse reactions (ARs) related to anti-tuberculosis (TB) drugs in children hospitalized for TB. A comprehensive understanding of these drug-related ARs may serve to improve patient prognosis. METHOD: Inpatients diagnosed with TB from 2008 to 2013 were enrolled retrospectively. The patients' demographics, diagnosis and ARs were recorded and analyzed for comprehensive evaluation...
January 3, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28058501/-cytokine-neutralization-at-specific-cellular-source-a%C3%A2-new-therapeutic-paradigm-german-version
#17
A A Kruglov, S A Nedospasov
BACKGROUND: Currently, treatment of autoimmune diseases is based on manipulation of general control mechanisms, including those mediated by immunoregulatory cytokines. This approach is non-curative and may cause unwanted side effects due to numerous beneficial and non-redundant functions of a particular cytokine. METHODS: Techniques of reverse genetics, such as conditional gene targeting, were employed to uncover the contributions of two proinflammatory and immunomodulatory cytokines, tumour necrosis factor (TNF) and interleukin 6 (IL-6), in various disease states...
January 5, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28057946/ismp-adverse-drug-reactions-sildenafil-induced-erythema-multiforme-acute-liver-injury-due-to-febuxostat-intravenous-acetaminophen-induced-acute-hepatotoxicity-acute-transient-myopia-induced-by-zanamivir-lidocaine-induced-hoigne-syndrome
#18
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: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
December 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/28056947/triptolide-induces-hepatotoxicity-via-inhibition-of-cyp450s-in-rat-liver-microsomes
#19
Yan Lu, Tong Xie, Yajie Zhang, Fuqiong Zhou, Jie Ruan, Weina Zhu, Huaxu Zhu, Zhe Feng, Xueping Zhou
BACKGROUND: Triptolide (TP), an active constituent of Tripterygium wilfordii, possesses numerous pharmacological activities. However, its effects on cytochrome P450 enzymes (CYP450s) in rats remain unexplored. METHODS: In this study, the effects of triptolide on the six main CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A) were investigated both in vivo and in vitro. We monitored the body weight, survival proportions, liver index, changes in pathology, and biochemical index upon TP administration, in vivo...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28053882/hepatoprotective-potential-of-ethanolic-extract-of-aquilaria-agallocha-leaves-against-paracetamol-induced-hepatotoxicity-in-sd-rats
#20
Janey Alam, Md Mujahid, Badruddeen, Yasmeen Jahan, Paramdeep Bagga, Md Azizur Rahman
Many traditional systems of medicines employ herbal drugs for the hepatoprotection. Aim of the study was designed to evaluate the hepatoprotective potential of 'ethanolic extract of Aquilaria agallocha ( Chen Xiang) leaves' (AAE) against paracetamol (PCM) induced hepatotoxicity in SD rats. Group I animals were treated with 1% CMC for 8 days. Group II, III, IV and V animals were first treated with '1% CMC' 1 ml/kg/day, AAE 200 mg/kg/day, AAE 400 mg/kg/day and silymarin 100 mg/kg/day respectively for 7 days and then, orally administered with PCM 3 g/kg b...
January 2017: Journal of Traditional and Complementary Medicine
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