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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/29662843/insulinotropic-effect-of-s-allyl-cysteine-in-rat-pups
#1
Busisani W Lembede, Jeanette Joubert, Pilani Nkomozepi, Kennedy H Erlwanger, Eliton Chivandi
S -Allyl cysteine (SAC) is found in garlic and has been reported to exert antidiabetic and antiobesity properties in drug-induced adult experimental models of metabolic dysfunction, but its potential beneficial effects in high-fructose diet neonatal rat models have not been determined. This study investigated the potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and female (n=32) Wistar rat pups, were randomly assigned to and administered the following treatment regimens daily for 15 days: group I, distilled water; group II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS...
March 2018: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29650854/-a-case-of-hyperammonemia-induced-by-chemotherapy-with-5-fluorouracil-for-metastatic-colon-cancer
#2
Shinji Tokuyama, Mutsumi Fukunaga, Ken Konishi, Shoko Honda, Ryohei Yukimoto, Aoi Okamoto, Akina Saito, Kazuyuki Okada, Hideo Ota, Shigekazu Yokoyama, Hirofumi Miki, Kenji Kobayashi
Systemic chemotherapy based on 5-fluorouracil(5-FU)is a standard treatment for unresectable or recurrent colon cancers. Here, we report a case of hyperammonemia induced by chemotherapy using 5-FU for metastatic colon cancer. An 84-yearold male patient with past histories of liver cirrhosis related to hepatitis C virus and renal dysfunction underwent an operation for the rectosigmoid colon cancer 8 years ago. Three years after that operation, a local recurrence of the colon cancer was diagnosed, and chemotherapy using sLV5FU2 was initiated...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29569382/case-of-lamotrigine-induced-drug-adverse-reaction-under-tocilizumab-treatment-with-clinical-and-virological-features-of-drug-induced-hypersensitivity-syndrome
#3
Hisato Iriki, Takeshi Ouchi, Hiromi Ito, Miho Sawada, Miho Mukai, Hisashi Nomura, Yuko Baba, Takeya Adachi, Takeru Funakoshi, Masayuki Amagai, Hayato Takahashi
The pathological mechanisms and immunological kinetics of drug-induced hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6, remain unclear. We report a case of drug adverse reaction that does not fulfill the diagnostic criteria of DIHS but mimics its characteristic features. Because the patient was under anti-IL-6 therapy at the onset, some symptoms typically seen in DIHS were absent, such as fever and leukocyte count abnormalities. However, the characteristic features of DIHS were clearly observed in the subsequent course, including the repeated recurrence of skin rash, prolonged liver dysfunction and reactivation of herpes viruses...
March 22, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29549244/effects-of-sildenafil-treatment-on-thermogenesis-and-glucose-homeostasis-in-diet-induced-obese-mice
#4
Kornelia Johann, Marlen Colleen Reis, Lisbeth Harder, Beate Herrmann, Sogol Gachkar, Jens Mittag, Rebecca Oelkrug
Stimulation of thermogenic pathways appears to be a promising approach to find new ways of tackling metabolic diseases like obesity and diabetes mellitus type 2. Thermogenic, weight reducing and insulin sensitizing effects of phosphodiesterase 5 (PDE 5) inhibitors have recently been postulated, suggesting that modulators of endogenous cGMP signaling have the therapeutic potential to treat metabolic disorders. However, most studies have been performed in vitro or in animals that were not glucose intolerant. We, thus, aimed to test the metabolic effects of the PDE 5 inhibitor sildenafil by treating diet-induced obese (DIO) mice orally for 8 days...
March 13, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29548626/treatment-of-acetaminophen-induced-liver-injury-with-exogenous-mitochondria-in-mice
#5
Xianxun Shi, Huiyuan Bai, Ming Zhao, Xiaorong Li, Xianchao Sun, Hongbo Jiang, Ailing Fu
Drug-induced liver injury shares a common feature of mitochondrial dysfunction. Mitochondrial therapy (mitotherapy), which replaces malfunctional mitochondria with functional exogenous mitochondria, may be a fundamental approach for treating drug-mediated hepatotoxicity. Here, we suggested that mitochondria isolated from human hepatoma cell could be used to treat acetaminophen (APAP)-induced liver injury in mice. When the mitochondria were added into the cell media, they could enter primarily cultured mouse hepatocyte...
March 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29540664/prebiotic-attenuation-of-olanzapine-induced-weight-gain-in-rats-analysis-of-central-and-peripheral-biomarkers-and-gut-microbiota
#6
Amy Chia-Ching Kao, Sonia Spitzer, Daniel C Anthony, Belinda Lennox, Philip W J Burnet
Olanzapine is an effective antipsychotic drug but since it causes significant weight gain, it is not well tolerated by psychosis patients. The prebiotic, B-GOS® , attenuates metabolic dysfunction in obese subjects, and in rodents, alters central NMDA receptors and may affect serotonin receptors that are relevant in psychosis. We have determined whether B-GOS® influenced olanzapine-associated weight gain and central NMDA and serotonin receptors. Circulating acetate, IL-1β, IL-8 and TNFα, liver acetyl-CoA carboxylase (ACC), white adipose tissue (WAT) acetate receptor GPR43, and specific faecal bacteria genera were also measured to provide mechanistic information...
March 15, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29530601/structural-patterns-of-the-human-abcc4-mrp4-exporter-in-lipid-bilayers-rationalize-clinically-observed-polymorphisms
#7
B Chantemargue, F Di Meo, K Berka, N Picard, H Arnion, M Essig, P Marquet, M Otyepka, P Trouillas
The ABCC4/MRP4 exporter has a clinical impact on membrane transport of a broad range of xenobiotics. It is expressed at key locations for drug disposition or effects such as in the liver, the kidney and blood cells. Several polymorphisms and mutations (e.g., p.Gly187Trp) leading to MRP4 dysfunction are associated with an increased risk of toxicity of some drugs. So far, no human MRP4 structure has been elucidated, precluding rationalization of these dysfunctions at a molecular level. We constructed atomistic model of the wild type (WT) MRP4 and the p...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29509265/plasma-exchange-combining-with-plasma-bilirubin-adsorption-effectively-removes-toxic-substances-and-improves-liver-functions-of-hepatic-failure-patients
#8
X-Q Che, Z-Q Li, Z Chen, D Guo, Q-Y Jia, S-C Jiang, J Cai
OBJECTIVE: Hepatic failure (HF) is a kind of complex disease characterizing with liver dysfunction and a few clinical complications. Artificial liver support system (ALSS) has been applied to HF patients to improve dysfunctional liver in recent years. This study aims to evaluate therapeutic effects of ALSS approaches, including plasma exchange (PE), plasma diafiltration (PDF) and plasma bilirubin adsorption (PBA), on liver function of HF patients. PATIENTS AND METHODS: This study is a retrospective analysis involving 516 patients diagnosed as HF between February 2014 and February 2015...
February 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29501571/integrated-omics-analysis-reveals-new-drug-induced-mitochondrial-perturbations-in-human-hepatocytes
#9
Jarno E J Wolters, Simone G J van Breda, Jonas Grossmann, Claudia Fortes, Florian Caiment, Jos C S Kleinjans
We performed a multiple 'omics study by integrating data on epigenomic, transcriptomic, and proteomic perturbations associated with mitochondrial dysfunction in primary human hepatocytes caused by the liver toxicant valproic acid (VPA), to deeper understand downstream events following epigenetic alterations in the mitochondrial genome. Furthermore, we investigated persistence of cross-omics changes after terminating drug treatment. Upon transient methylation changes of mitochondrial genes during VPA-treatment, increasing complexities of gene-interaction networks across time were demonstrated, which normalized during washout...
February 28, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29457989/propylthiouracil-induced-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-mimicking-kawasaki-disease
#10
Yoshihiro Aoki, Katsuhiko Kitazawa, Hironobu Kobayashi
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children and is characterised as necrotising vasculitis predominantly affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD) is a common systemic vasculitis, typically observed in children, which affects the medium-sized vessels, including the coronary arteries. An 11-year-old girl who developed AAV while receiving PTU therapy for Graves' disease is described...
February 19, 2018: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/29438557/is-drug-induced-hepatitis-related-to-the-severity-of-tuberculous-meningitis
#11
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
#12
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
#13
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 25, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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