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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/29438557/is-drug-induced-hepatitis-related-to-the-severity-of-tuberculous-meningitis
#1
Mritunjai Kumar, Jayantee Kalita, Abhilasha Tripathi, Usha K Misra
Background: Drug-induced hepatitis (DIH) occurs more commonly in tuberculous meningitis (TBM) than non-CNS tuberculosis. We evaluate DIH in TBM and its relationship with disease severity and surrogate markers of stress. Methods: Sixty-seven patients with TBM were included prospectively. The diagnosis of DIH was based on five times elevation of alanine amino transferase (ALT) in asymptomatic and three times in symptomatic patients, serum bilirubin 1.5 mg/dL or more occurring after 3 days of antitubercular drugs without any other cause of liver dysfunction; and improvement in liver function upon drug withdrawal...
February 9, 2018: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#2
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29407983/novel-enmein-type-diterpenoid-hybrids-coupled-with-nitrogen-mustards-synthesis-of-promising-candidates-for-anticancer-therapeutics
#3
Xiang Gao, Jia Li, Mingying Wang, Shengtao Xu, Weiwei Liu, Linghe Zang, Zhanlin Li, Huiming Hua, Jinyi Xu, Dahong Li
Natural derived enmein-type diterpenoids exert cytotoxicity against a wide range of human cancer cells. Yet their medicinal applications are hindered by insufficient potency for chemotherapy. Hence, a series of novel enmein-type diterpenoid hybrids coupled with nitrogen mustards were designed and synthesized to increase antitumor efficacy while reducing systemic toxicity. Most conjugates exhibited stronger antiproliferative activities than parent diterpenoids and nitrogen mustards, especially for multidrug-resistant tumor cell line Bel-7402/5-FU...
February 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29407200/interplay-of-gender-age-and-drug-properties-on-reporting-frequency-of-drug-induced-liver-injury
#4
Nayana George, Minjun Chen, Nancy Yuen, Christine M Hunt, Ayako Suzuki
We examined the effect of gender, age, and drug properties on liver events reporting frequency (RF) to assess patient- and drug-related risks for drug-induced liver injury (DILI). We performed a data-mining analysis of the WHO VigiBase™ to 1) identify drugs with gender- and age-biased RF and 2) characterize drug properties using the Liver Toxicity Knowledge Base. Age-, gender-specific Empirical Bayes Geometric Mean of relative reporting ratio of liver events with 90% confidence interval (CI) was calculated for 375 drugs with DILI potential...
January 29, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29403081/hepatotoxicity-of-immune-checkpoint-inhibitors-a-histology-study-of-seven-cases-in-comparison-with-autoimmune-hepatitis-and-idiosyncratic-drug-induced-liver-injury
#5
Yoh Zen, Matthew M Yeh
The adverse effects of immune checkpoint inhibitors in various organs may be attributed to immune-mediated processes triggered by disrupted self-tolerance; however, it remains unclear whether they are similar or dissimilar to classic organ-specific autoimmune diseases. The present study aimed to compare clinicopathologic features between checkpoint inhibitor-induced liver injury and acutely presenting autoimmune hepatitis or idiosyncratic drug-induced liver injury. Seven patients treated with nivolumab (n = 5) or ipilimumab (n = 2) presented with liver dysfunction a median of 41 days (range 21-120) after the initiation of immunotherapy...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29390572/acute-liver-failure-caused-by-pembrolizumab-in-a-patient-with-pulmonary-metastatic-liver-cancer-a-case-report
#6
Zhenping Wu, Lingling Lai, Ming Li, Lunli Zhang, Wenfeng Zhang
RATIONALE: Keytruda (pembrolizumab) is an inhibitor of programmed cell death receptor-1 (PD-1), which was approved to treat advanced melanoma and nonsmall cell lung cancer patients who do not respond to other treatment. However, its efficacy and security in the treatment of advanced liver cancer is still under investigation. PATIENT CONCERNS: A 60-year-old man was diagnosed with pulmonary metastatic liver cancer who accepted pembrolizumab treatment after the failure of sorafenib...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29385569/dronedarone-induced-cardiac-mitochondrial-dysfunction-and-its-mitigation-by-epoxyeicosatrienoic-acids
#7
Aneesh Karkhanis, Jacqueline Wen Hui Leow, Thilo Hagen, Eric Chun Yong Chan
Dronedarone and amiodarone are structurally similar antiarrhythmic drugs. Dronedarone worsens cardiac adverse effects with unknown causes while amiodarone has no cardiac adversity. Dronedarone induces preclinical mitochondrial toxicity in rat liver and exhibits clinical hepatotoxicity. Here, we further investigated the relative potential of the antiarrhythmic drugs in causing mitochondrial injury in cardiomyocytes. Differentiated rat H9c2 cardiomyocytes were treated with dronedarone, amiodarone and their respective metabolites namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA)...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29382127/the-implication-of-the-brain-insulin-receptor-in-late-onset-alzheimer-s-disease-dementia
#8
REVIEW
Jaume Folch, Miren Ettcheto, Oriol Busquets, Elena Sánchez-López, Rubén D Castro-Torres, Ester Verdaguer, Patricia R Manzine, Saghar Rabiei Poor, María Luisa García, Jordi Olloquequi, Carlos Beas-Zarate, Carme Auladell, Antoni Camins
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline...
January 29, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29367368/lamotrigine-induced-drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-during-primary-epstein-barr-virus-ebv-infection
#9
Ibrahim Tawhari, Fawaz Tawhari, Mossab Aljuaid
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening idiosyncratic drug reaction that may result in skin eruption, mucous membrane involvement, eosinophilia, atypical lymphocytosis and lymphadenopathy, with wide-ranging internal organ involvement. The authors report the case of a 21-year-old man who was prescribed lamotrigine for anxiety disorder. After 2 weeks of treatment, he developed a pruritic morbilliform rash on his trunk and upper extremities that was associated with fever, sore throat, bilateral scleral injection, nausea, vomiting and abdominal pain...
January 23, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29321828/exendin-4-protects-mice-from-d-galactose-induced-hepatic-and-pancreatic-dysfunction
#10
Akram Ahangarpour, Ali Akbar Oroojan, Mohammad Badavi
Investigations into pharmaceutical intervention of pancreatic and hepatic dysfunction associated with metabolic disturbances have received relatively little attention. The aim of this study was to investigate the protective effects of exendin-4 in mice receiving D-galactose, a reducing sugar that triggers ROS production and inflammatory mediators affecting the pancreas and liver. Exendin-4 is an United States Food and Drug Administration (FDA) approved glucagon-like peptide that increases insulin dependent glycogen synthesis and glucose uptake...
2018: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/29232800/-a-case-of-fulminant-hepatitis-after-administration-of-abiraterone-acetate
#11
Satoru Yumiba, Kazuhiko Komori, Toshichika Iwanishi, Youhei Koida, Masao Kobayashi, Yutaka Ono
A 77-year-old man with castration-resistant prostate cancer (CRPC) received abiraterone acetate in October 2014. He visited our outpatient clinic because of general malaise and anorexia 27 days after starting abiraterone acetate. The lab test showed hepatic dysfunction (aspartate transaminase, AST 440 U/l, alanine transaminase, ALT 420 U/l) and the elevation of liver enzymes continued on the next day even after stopping abiraterone acetate. Three days later, he was hospitalized due to severe elevation of liver enzymes (AST 1,171 U/l, ALT 1,487 U/l) , and the decreased prothrombin activity (60...
November 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/29224108/negative-impact-of-testosterone-deficiency-and-5%C3%AE-reductase-inhibitors-therapy-on-metabolic-and-sexual-function-in-men
#12
Abdulmaged M Traish
Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5α-dihydrotestosterone (5α-DHT) or via aromatization into estradiol (E2) modulates important biochemical signaling pathways of human physiology and plays a critical role in the growth and/or maintenance of functions in a host of tissues and organs. T and 5α-DHT play an important role in regulating physiology of the muscle, adipose tissue, liver, bone, and central nervous system, as well as reproductive and sexual functions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29209440/efficacy-of-fenugreek-based-bionanocomposite-on-renal-dysfunction-and-endogenous-intoxication-in-high-calorie-diet-induced-obesity-rat-model-comparative-study
#13
Victoria V Konopelniuk, Ievgenii I Goloborodko, Tetyana V Ishchuk, Tetyana B Synelnyk, Ludmila I Ostapchenko, Mykola Ya Spivak, Rostyslav V Bubnov
Background: Worldwide obesity spread is a global health problem and needs to be further studied. Co-morbidities of obesity include insulin resistance, diabetes mellitus type 2, and dyslipidemia, which are the most frequent contributing factors for metabolic syndrome (MetS), as well as non-alcoholic fatty liver disease and chronic kidney disease. The aim was to study renal function and endogenous intoxication panel on high-calorie diet-induced obesity rat model and perform comparative study of the treatment efficacy of Fenugreek-based bionanocomposite vs antiobesogenic drugs (Orlistat)...
December 2017: EPMA Journal
https://www.readbyqxmd.com/read/29190729/increased-mmab-level-in-mitochondria-as-a-novel-biomarker-of-hepatotoxicity-induced-by-efavirenz
#14
Zhimi Tan, Xiaofang Jia, Fang Ma, Yanling Feng, Hongzhou Lu, Jun-O Jin, Dage Wu, Lin Yin, Li Liu, Lijun Zhang
BACKGROUND: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), has been widely used in the therapy of human immunodeficiency virus (HIV) infection. Some of its toxic effects on hepatic cells have been reported to display features of mitochondrial dysfunction through bioenergetic stress and autophagy, etc. However, alteration of protein levels, especially mitochondrial protein levels, in hepatic cells during treatment of EFV has not been fully investigated. METHODS: We built a cell model of EFV-induced liver toxicity through treating Huh-7 cells with different concentrations of EFV for different time followed by the analysis of cell viability using cell counting kit -8 (CCK8) and reactive oxygen species (ROS) using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSox dye...
2017: PloS One
https://www.readbyqxmd.com/read/29187717/-a-case-of-liver-dysfunction-requiring-hospital-admission-after-taking-oral-itraconazole-for-the-treatment-of-kerion-celsi
#15
Eri Ikeda, Soko Watanabe, Mizuki Sawada, Junya Ninomiya, Itaru Dekio, Sumiko Ishizaki, Mariko Fujibayashi, Masaru Tanaka, Takashi Harada
  67-year-old female patient developed drug-induced liver dysfunction after taking oral itraconazole (ITCZ) for the treatment of kerion celsi. Red papules appeared on the temporal area of the patient one month prior to her visit to our clinic. The patient presented with a nodule with yellow crust, erosion, infiltration, and hair loss on the area. Diagnosis of kerion celsi caused by Trichophyton rubrum was made from clinical, pathological, and mycological findings. Laboratory data showed normal liver function, and the patient was not taking any other medication, thus, daily oral ITCZ 100 mg was started...
2017: Medical Mycology Journal
https://www.readbyqxmd.com/read/29154799/integrative-omics-data-analyses-of-repeated-dose-toxicity-of-valproic-acid-in-vitro-reveal-new-mechanisms-of-steatosis-induction
#16
Simone G J van Breda, Sandra M H Claessen, Marcel van Herwijnen, Daniël H J Theunissen, Danyel G J Jennen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of VPA for 5days daily which induced lipid accumulation. Part of the PHH was left untreated for 3days for studying the persistence of 'omics' changes...
November 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29115483/hepatocellular-toxicity-of-oxalicumone-a-via-oxidative-stress-injury-and-mitochondrial-dysfunction-in-healthy-human-liver-cells
#17
Si Shi, Limei Yao, Kunbin Guo, Xiangyu Wang, Qi Wang, Weirong Li
The marine‑derived oxalicumone A (POA) has been demonstrated as a potent anti‑tumor bioactive agent for a variety of human carcinoma, but to the best of our knowledge, remains to be evaluated in healthy liver cells. As many drugs distribute preferentially in the liver, the present study aimed to investigate the effects of POA on apoptosis, oxidative stress and mitochondrial function in L‑02 healthy liver cells. A Cell‑Counting kit‑8 assay demonstrated that POA inhibits the proliferation of L‑02 cells in a dose‑ and time‑dependent manner...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29082485/tools-to-measure-cell-health-and-cytotoxicity-using-high-content-imaging-and-analysis
#18
Bhaskar S Mandavilli, Robert J Aggeler, Kevin M Chambers
High content screening (HCS)-based multiparametric measurements are very useful in early toxicity testing and safety assessment during drug development, and useful in evaluating the impact from new food supplements and environmental toxicants. Mitochondrial membrane potential, plasma membrane permeability, oxidative stress, phosphoplipidosis, and steatosis are a few of the important markers routinely studied for the assessment of drug-induced liver injury and toxicity. Mitochondrial dysfunction leads to oxidative stress and cell death...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29027371/differential-proteomic-analysis-of-dimethylnitrosamine-dmn-induced-liver-fibrosis
#19
Xiujie Liu, Rongji Dai, Ming Ke, Imran Suheryani, Weiwei Meng, Yulin Deng
Liver fibrosis is a common pathological feature of many chronic liver diseases. To characterize the entire panorama of proteome changes in DMN-induced liver fibrosis, iTRAQ-based differential proteomic analysis was performed with DMN-induced liver fibrosis rats. A total of 4155 confidently identified proteins were found, with 365 proteins showing significant changes (fold changes of >1.5 or < 0.67, P < 0.05). In metabolic activation, proteins assigned to drug metabolism enzymes (e.g., CYP2D1) changed, suggesting that the liver protection mechanism was activated to relieve DMN toxicity...
October 13, 2017: Proteomics
https://www.readbyqxmd.com/read/29026167/the-proteasome-inhibitor-bortezomib-attenuates-renal-fibrosis-in-mice-via-the-suppression-of-tgf-%C3%AE-1
#20
Moko Zeniya, Takayasu Mori, Naofumi Yui, Naohiro Nomura, Shintaro Mandai, Kiyoshi Isobe, Motoko Chiga, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Kidney fibrosis and fibrogenesis significantly exacerbate chronic kidney disease (CKD) progression and are essential therapeutic targets. Bortezomib (BZM) is a proteasome inhibitor used for the treatment of multiple myeloma (MM). Several studies have demonstrated that BZM attenuates renal impairment in patients with MM, although this effect is generally considered to be the result of MM remission. Recently, several studies on BZM reported anti-fibrotic effects on liver and skin in experimental animal models...
October 12, 2017: Scientific Reports
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