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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/28331914/effects-and-mechanisms-of-a-new-multivitamin-on-chronic-metabolic-syndromes-and-aging
#1
Su-Xi Wu, Xuewei Jiang, Yu-Ying Liu, Lin-Feng Chen, Jun Tao
BACKGROUND: Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. MATERIAL AND METHODS: Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#2
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/28304119/serum-markers-for-mitochondrial-dysfunction-and-cell-death-are-possible-predictive-indicators-for-drug-induced-liver-injury-by-direct-acting-antivirals
#3
Keisuke Kakisaka, Yuichi Yoshida, Yuji Suzuki, Takuro Sato, Hidekatsu Kuroda, Akio Miyasaka, Yasuhiro Takikawa
BACKGROUND & AIM: We prospectively screened patients treated with direct-acting antivirals (DAAs) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). METHODS: The levels of various serum markers among DILI, non-DILI, and control groups were compared. The DILI group consisted of 8 patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, gender, and disease severity...
March 17, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28261831/hydroxyapatite-nanoparticle-induced-mitochondrial-energy-metabolism-impairment-in-liver-cells-in-vitro-and-in-vivo-studies
#4
Yang Xue, Qingqing Chen, Jiao Sun
Hydroxyapatite nanoparticles (HAP-NPs) have been extensively developed as drug carriers, bone implants, coating materials, etc. in the human body. However, research focusing on the potential side effects of HAP-NPs on the mitochondria-associated energy metabolism in liver cells is lacking. In this study, HAP-NPs with a long diameter of 80 nm and a short diameter of 20 nm were evaluated for their ability to induce mitochondrial energy metabolism dysfunction in vitro and in vivo. In the in vitro system, the buffalo rat hepatocyte (BRL) cell line was directly exposed to the HAP-NPs...
March 6, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28242362/intravenous-administration-of-mitochondria-for-treating-experimental-parkinson-s-disease
#5
Xianxun Shi, Ming Zhao, Chen Fu, Ailing Fu
Mitochondrial dysfunction is associated with a large number of human diseases, including neurological and muscular degeneration, cardiovascular disorders, obesity, diabetes, aging and rare mitochondrial diseases. Replacement of dysfunctional mitochondria with functional exogenous mitochondria is proposed as a general principle to treat these diseases. Here we found that mitochondria isolated from human hepatoma cell could naturally enter human neuroblastoma SH-SY5Y cell line, and when the mitochondria were intravenously injected into mice, all of the mice were survived and no obvious abnormality appeared...
February 24, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28224373/drug-induced-liver-injury-in-the-setting-of-glycogenic-hepatopathy
#6
Valmiki Maharaj, Matthew Fitz, Xianzdong Ding
Glycogenic hepatopathy (GH) is an underdiagnosed complication of uncontrolled type 1 diabetes mellitus (T1DM). It appears as an acute relapsing hepatitis with reversible transaminase elevations secondary to excessive hepatic glycogen accumulation. Patients are often asymptomatic but can present with abdominal pain, nausea and vomiting. Physical examination shows hepatomegaly without splenomegaly. GH is diagnosed by biopsy as it is clinically indistinguishable from non-alcoholic fatty liver disease (NAFLD), a more common cause of hepatic dysfunction in diabetics...
February 21, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#7
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using (1)H NMR based serum metabolomics...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#8
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28177750/modulatory-role-of-co-enzyme-q10-on-methionine-and-choline-deficient-diet-induced-non-alcoholic-steatohepatitis-nash-in-albino-rats
#9
Dalia O Saleh, Rania F Ahmed, Mohamed M Amin
The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day)(-1)) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded...
March 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28161274/valproate-acid-vpa-induced-dysmetabolic-function-in-clinical-and-animal-studies
#10
Rong Li, Lisheng Liang, Xinmou Wu, Xianli Ma, Min Su
BACKGROUND: Valproate acid (VPA), a commonly used antiepileptic medicine, is found to be linked to developing dysmetabolic risk. However, the proposed mechanism remains completely unknown. METHODS: In this study, we collected data from patients with epilepsy and further investigated the preclinical study in mice. RESULTS: As results, the clinical data showed that VPA-used patients resulted in higher levels of blood glucose, urine acid, triglyceride (TG), and immune cells (leucocyte, neutrophil leucocyte) when compared to clinically diagnosed references, while circulating apolipoprotein A1 (Apob A1) and fatty acid binding protein 4 (FABP4) were reduced without visible drug-induced liver injury (DILI)...
February 2, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#11
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
https://www.readbyqxmd.com/read/28115652/candidate-risk-factors-and-mechanisms-for-tolvaptan-induced-liver-injury-are-identified-using-a-collaborative-cross-approach
#12
Merrie Mosedale, Yunjung Kim, William J Brock, Sharin E Roth, Tim Wiltshire, J Scott Eaddy, Gregory R Keele, Robert W Corty, Yuying Xie, William Valdar, Paul B Watkins
Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains...
January 23, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28109684/increase-in-the-systemic-exposure-of-primary-metabolites-of-midazolam-in-rat-arising-from-cyp-inhibition-or-hepatic-dysfunction
#13
Tsubasa Hasegawa, Satomi Nakanishi, Keiko Minami, Haruki Higashino, Makoto Kataoka, Yoshihisa Shitara, Shinji Yamashita
The main purpose of this study is to demonstrate the possibility of increase in the systemic exposure of drug metabolites by CYP-inhibition or acute hepatitis. Midazolam (MDZ) was used as a model substrate of CYP3A and 1-aminobenzotriazole (ABT) was used as a CYP-inhibitor. After oral pretreatment with ABT, MDZ was intravenously injected to rats and the plasma profiles of MDZ and its primary metabolites, 1'-hydroxy MDZ and 4-hydroxy MDZ, were observed. In the ABT-pretreatment rats, plasma AUCs of both metabolites were much larger than those in control rats, demonstrating a higher systemic exposure of metabolites under CYP-inhibited condition...
November 23, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28100990/drug-induced-liver-injury-associated-with-complementary-and-alternative-medicines
#14
Koji Takahashi, Tatsuo Kanda, Shin Yasui, Yuki Haga, Junichiro Kumagai, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Masato Nakamura, Makoto Arai, Osamu Yokosuka
A 24-year-old man was admitted due to acute hepatitis with unknown etiology. After his condition and laboratory data gradually improved with conservative therapy, he was discharged 1 month later. Two months after his discharge, however, liver dysfunction reappeared. After his mother accidentally revealed that he took complementary and alternative medicine, discontinuation of the therapy caused his condition to improve. Finally, he was diagnosed with a recurrent drug-induced liver injury associated with Japanese complementary and alternative medicine...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#15
K Yang, C Battista, J L Woodhead, S H Stahl, J T Mettetal, P B Watkins, S Q Siler, B 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 (PBPK) 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/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#16
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28024294/celecoxib-administration-reduced-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-injury-in-septic-rats
#17
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP)...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28000142/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-with-teicoplanin-a-case-report
#18
Sholeh Ebrahimpour, Mehdi Mohammadi, Kheirollah Gholami
Intramuscular teicoplanin (400 mg every 12 h for three doses, then 400 mg daily, intramuscularly) was prescribed for a 37-year-old woman with presumptive diagnosis of cellulitis. On the 14th day of treatment, she developed generalized maculopapular rash, accompanied by fever, wheezing, shortening of breath, and lymphadenopathy. Lab tests revealed abnormal liver enzymes, leukocytosis, and eosinophilia. The treatment was interrupted with suspicion of drug reaction. Fever subsided after 48 h. Skin eruption and respiratory symptoms began to resolve within 2 weeks...
December 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27995280/dietary-fructose-as-a-risk-factor-for-non-alcoholic-fatty-liver-disease-nafld
#19
REVIEW
Salamah Mohammad Alwahsh, Rolf Gebhardt
Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD...
December 19, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27993716/the-fxr-agonist-px20606-ameliorates-portal-hypertension-by-targeting-vascular-remodelling-and-sinusoidal-dysfunction
#20
Philipp Schwabl, Eva Hambruch, Berit A Seeland, Hubert Hayden, Michael Wagner, Lukas Garnys, Bastian Strobel, Tim-Lukas Schubert, Florian Riedl, Dieter Mitteregger, Michael Burnet, Patrick Starlinger, Georg Oberhuber, Ulrich Deuschle, Nataliya Rohr-Udilova, Bruno K Podesser, Markus Peck-Radosavljevic, Thomas Reiberger, Claus Kremoser, Michael Trauner
BACKGROUND & AIMS: Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. METHODS: In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl4, 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged...
December 18, 2016: Journal of Hepatology
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