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Drug-induced hepatotoxicity

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https://www.readbyqxmd.com/read/29340156/hepatotoxicity-in-hyperthyroid-patient-after-consecutive-methimazole-and-propylthiouracil-therapies
#1
Fernando Gomez-Peralta, Pablo Velasco-Martínez, Cristina Abreu, María Cepeda, Marta Fernández-Puente
Methimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs (ATD) that have been approved for the treatment of hyperthyroidism. Hepatotoxicity may be induced by these drugs, though they exert dissimilar incidence rates of hepatotoxicity and, possibly, with different underlying pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant medical history diagnosed with hyperthyroidism due to Graves' disease, who developed two episodes of acute hepatitis concurrent with the consecutive administration of two different ATDs, first MMI and then PTU...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29339102/spirulina-ameliorates-methotrexate-hepatotoxicity-via-antioxidant-immune-stimulation-and-proinflammatory-cytokines-and-apoptotic-proteins-modulation
#2
Asmaa F Khafaga, Yasser S El-Sayed
AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, MTX (20 mg/kg bwt, single ip injection), SP (500 mg/kg bwt, oral gavage daily for 21 days), and MTX+SP...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#3
Liang Shi, Zhanxia Hao, Shaobo Zhang, Mengjuan Wei, Bin Lu, Zhengtao Wang, Lili Ji
Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29337684/hepatotoxicity-associated-with-statins
#4
Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk, Yağmur Özkan
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29333041/pharmacological-evaluation-of-hepatoprotective-activity-of-ahpl-aytab-0613-tablet-in-carbon-tetrachloride-ethanol-and-paracetamol-induced-hepatotoxicity-models-in-wistar-albino-rats
#5
Sanjay U Nipanikar, Sohan S Chitlange, Dheeraj Nagore
Background: Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe. Objective: Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#6
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29329425/comparison-of-hepatic-2d-sandwich-cultures-and-3d-spheroids-for-long-term-toxicity-applications-a-multi-center-study
#7
Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris Goldring, Kevin Park, Sophie Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Primary human hepatocytes (PHH) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHH are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the six participating laboratories evaluated the robustness of these two model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-lab variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms...
January 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29323538/clinical-characteristics-and-outcomes-of-traditional-chinese-medicine-induced-liver-injury-a-systematic-review
#8
Ran Wang, Xingshun Qi, Eric Yoshida, Nahum Mendez-Sanchez, Rolf Teschke, Mingyu Sun, Xu Liu, Chunping Su, Jiao Deng, Han Deng, Feifei Hou, Xiaozhong Guo
BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. AIMS: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). METHODS: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched...
January 11, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29321478/reprogramming-of-pro-inflammatory-human-macrophages-to-an-anti-inflammatory-phenotype-by-bile-acids
#9
Marianne Wammers, Anna-Kathrin Schupp, Johannes G Bode, Christian Ehlting, Stephanie Wolf, René Deenen, Karl Köhrer, Dieter Häussinger, Dirk Graf
Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the presence or absence of LPS...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319136/the-use-of-99mtc-phytate-for-assessment-the-protective-effect-of-vitamin-e-against-hepatotoxicity-induced-by-methotrexat-in-rat
#10
Hossein Amirfakhrian, Seyed Mohammad Abedi, Hossein Sadeghi, Soheil Azizi, Seyed Jalal Hosseinimehr
In this study, we investigated the protective effect of vitamin E against methotrexate (MTX)-induced hepatotoxicity by quantitative liver 99mTc-phytate uptake and liver imaging and to compare its effect with histopathology in rat. Rats were divided into five groups as control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg), Vit E + MTX and. Vit E was intraperitoneally administrated for 17 days before MTX injection and continued for 4 days. 99mTc-phytate was injected through the tail of rats after the drug administration...
January 10, 2018: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/29304113/discovery-of-indolylpiperazinylpyrimidines-with-dual-target-profiles-at-adenosine-a2a-and-dopamine-d2-receptors-for-parkinson-s-disease-treatment
#11
Yi-Ming Shao, Xiaohua Ma, Priyankar Paira, Aaron Tan, Deron Raymond Herr, Kah Leong Lim, Chee Hoe Ng, Gopalakrishnan Venkatesan, Karl-Norbert Klotz, Stephanie Federico, Giampiero Spalluto, Siew Lee Cheong, Yu Zong Chen, Giorgia Pastorin
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects...
2018: PloS One
https://www.readbyqxmd.com/read/29301090/evaluation-of-therapeutic-effect-of-rice-husk-silica-combined-with-platelets-derived-growth-factor-in-hepatic-veno-occlusive-disease
#12
Eithar K Al Adham, Amal I Hassan, M M Hazem, Ahmed Shebl
Veno- occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study aimed to investigate the possible therapeutic impact of rice husk silica (RHS) nanoparticles combined with a platelet-derived growth factor (PDGF) on the Veno-occlusive disease in liver (VOD) elicited by dactinomycin (DAC) in rats. Forty-eight male Sprague-Dawely rats were classified into six groups, 8 rats each. The first group served as control, the second, animals were infused by intraperitoneal injection with DAC (0...
January 4, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29283882/sildenafil-a-phosphodiesterase-5-inhibitor-offers-protection-against-carbon-tetrachloride-induced-hepatotoxicity-in-rat
#13
Olorunfemi R Molehin, Anne A Adeyanju, Stephen A Adefegha, Oluwasanmi O Aina, Blessing A Afolabi, Ayorinde O Olowoyeye, Jesutomi A Oyediran, Opeyemi R Oladiran
BACKGROUND: Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5'-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4). METHODS: CCl4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline...
December 28, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29279717/the-evaluation-of-toxicity-induced-by-psoraleae-fructus-in-rats-using-untargeted-metabonomic-method-based-on-uplc-q-tof-ms
#14
Yanyan Xu, Yiwei Zhao, Jiabin Xie, Xue Sheng, Yubo Li, Yanjun Zhang
Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29262297/antiallodynic-and-antihyperalgesic-activity-of-new-3-3-diphenyl-propionamides-with-anticonvulsant-activity-in-models-of-pain-in-mice
#15
Anna Rapacz, Jolanta Obniska, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Agata Siwek, Anna Gryboś, Sabina Rybka, Aleksandra Karcz, Elżbieta Pękala, Barbara Filipek
Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic pain. The aim of the present experiments was to examine analgesic activity of three new 3,3-diphenyl-propionamides, which had previously demonstrated anticonvulsant activity in the MES (maximal electroshock seizure), scPTZ (subcutaneous pentylenetetrazole) and/or 6Hz (psychomotor seizure) tests in mice. Antinociceptive activity was examined in mouse models of acute pain (the hot plate test) and tonic pain (the formalin test) in mice...
December 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29248475/alleviating-the-hepatotoxicity-of-trazodone-via-supramolecular-encapsulation
#16
Qiaoxian Huang, Shengke Li, Hang Yin, Chunming Wang, Simon M Y Lee, Ruibing Wang
In order to develop a novel strategy to alleviate the inherent hepatotoxicity of antidepressant trazodone (TZ), Cucurbit[7]uril (CB[7]) was adopted as pharmaceutical excipients and was studied for its capability to reduce the hepatotoxicity of TZ via supramolecular encapsulation. CB[7] was found to form strong 1:1 host-guest complexes with TZ and its metabolite m-chlorophenyl piperazine (mCPP), with binding constants of 1.50 (±0.13) × 106 M-1 and 6.90 (±0.49) × 105 M-1, respectively. The supramolecular complexations were examined by 1H NMR and UV-visible spectroscopic titrations, ESI-MS and ITC...
December 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29230302/letrozole-induced-hepatitis-with-autoimmune-features-a-rare-adverse-drug-reaction-with-review-of-the-relevant-literature
#17
Bharatsinh Gharia, Karan Seegobin, Satish Maharaj, Noor Marji, Amie Deutch, Lara Zuberi
While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis...
November 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29222033/multiple-perspectives-of-qingkailing-injection-fraction-single-compound-in-revealing-the-hepatotoxicity-of-baicalin-and-hyodeoxycholic-acid
#18
Jiayu Zhang, Shifeng Wang, Lulu Xu, Qiao Zhang, Zhanpeng Shang, Yanling Zhang, Qinghua Wu, Shiyou Li, Yanjiang Qiao
ETHNOPHARMACOLOGICAL RELEVANCE: The complexity of ingredients in traditional Chinese medical formulas and the limited consideration of toxicological responses are fundamental issues that hamper prognostic information of drug quality control. MATERIALS AND METHODS: A multidisciplinary approach for quality control of Qingkailing injection (QKL) regarding drug induced liver toxicity was described for the first time. High content image analysis (HCA) was combined with reverse-phase chromatographic separation and high-resolution MS detection technologies to provide the dynamic responses of HepG2 cell injury...
December 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29221149/prediction-on-the-risk-population-of-idiosyncratic-adverse-reactions-based-on-molecular-docking-with-mutant-proteins
#19
Hongbo Xie, Diheng Zeng, Xiujie Chen, Diwei Huo, Lei Liu, Denan Zhang, Qing Jin, Kehui Ke, Ming Hu
Idiosyncratic adverse drug reactions are drug reactions that occur rarely and unpredictably among the population. These reactions often occur after a drug is marketed, which means that they are strongly related to the genotype of the population. The prediction of such adverse reactions is a major challenge because of the lack of appropriate test models during the drug development process. In this study, we chose withdrawn drugs because the reasons why they were withdrawn and from which countries or regions is easily obtained...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217891/trimethoprim-sulfamethoxazole-induced-hepatotoxicity-in-a-renal-transplant-patient
#20
R Slim, N Asmar, C Yaghi, K Honein, R Sayegh, D Chelala
Drug-induced liver injury (DILI) represents liver damage from various therapeutic drugs. Antimicrobials are among the most common causes of DILI. We report a case of hepatic toxicity due to Trimethoprim-sulfamethoxazole (TMP-SMX) in a patient who underwent renal transplantation. Diagnosis has been made after a careful history taking, exclusion of competing etiologies and reversal of biochemical abnormalities after withdrawal of the antibiotic. TMP-SMX liver toxicity is well known but remains unpredictable and is rarely reported...
November 2017: Indian Journal of Nephrology
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