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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/29027371/differential-proteomic-analysis-of-dimethylnitrosamine-dmn-induced-liver-fibrosis
#1
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
#2
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
https://www.readbyqxmd.com/read/29018486/serum-and-liver-tissue-metabonomic-study-on-fatty-liver-in-rats-induced-by-high-fat-diet-and-intervention-effects-of-traditional-chinese-medicine-qushi-huayu-decoction
#3
Xiao-Jun Gou, Qin Feng, Lin-Lin Fan, Jian Zhu, Yi-Yang Hu
Qushi Huayu Decoction (QSHY), clinically derived, consists of five crude drugs, commonly used in treating fatty liver in a clinical setting. However, little is known about its metabolomics study. Herein, the serum and liver tissue metabolomics approach, based on gas chromatography coupled to spectrometry (GC/MS), was employed to evaluate the efficacy and the mechanism underlying QSHY in a rat model of high-fat diet-induced fatty liver. With pattern recognition analysis of serum and liver tissue metabolite profile, a clear separation of model group and control group was acquired for serum and liver tissue samples, respectively...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28966228/sensory-axonal-polyneuropathy-due-to-2-4-dinitrophenol
#4
Shintaro Izumoto, Akitoshi Taniguchi, Hitoshi Mochizuki, Kazutaka Shiomi, Masamitsu Nakazato
A 24-year-old man developed subacute onset of numbness and pain in the upper and lower limbs. Physical examination demonstrated decreased pinprick sensation, but was otherwise normal. Blood and cerebrospinal fluid parameters were normal except for mild hepatic dysfunction. No data were suggestive of connective tissue disease. Nerve conduction studies demonstrated sensory neuropathy. A detailed medical interview revealed that the patient had been taking self-imported 2,4-dinitrophenol (DNP) for 2 months to decrease body weight...
September 30, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28955042/acid-sphingomyelinase-inhibition-prevents-development-of-sepsis-sequelae-in-the-murine-liver
#5
Ha-Yeun Chung, C Julius Witt, Nayla Jbeily, Jorge Hurtado-Oliveros, Benjamin Giszas, Amelie Lupp, Markus H Gräler, Tony Bruns, Andreas Stallmach, Falk A Gonnert, Ralf A Claus
The molecular mechanisms of maladaptive response in liver tissue with respect to the acute and post-acute phase of sepsis are not yet fully understood. Long-term sepsis survivors might develop hepatocellular/hepatobiliary injury and fibrosis. Here, we demonstrate that acid sphingomyelinase, an important regulator of hepatocyte apoptosis and hepatic stellate cell (HSC) activation, is linked to the promotion of liver dysfunction in the acute phase of sepsis as well as to fibrogenesis in the long-term. In both phases, we observed a beneficial effect of partial genetic sphingomyelinase deficiency in heterozygous animals (smpd1(+/-)) on oxidative stress levels, hepatobiliary function, macrophage infiltration and on HSC activation...
September 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28930961/impact-of-a-novel-phosphoinositol-3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#6
George Edward Black, Kyle K Sokol, Donald M Moe, Jon D Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhaylo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental phosphoinositol-3 kinase (PI3-K) inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage-associated molecular patterns (DAMPs)...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28888756/renoprotective-effect-of-the-xanthine-oxidoreductase-inhibitor-topiroxostat-under-decreased-angiotensin-ii-type-1a-receptor-expression
#7
Keiichi Ohata, Atsuko Kamijo-Ikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Kimie Katayama, Junko Asano, Kenjiro Kimura, Yugo Shibagaki
The aim of this study was to confirm the renoprotective effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a(+/-)L-FABP(+/-))...
September 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28869295/the-clinical-potential-of-senolytic-drugs
#8
James L Kirkland, Tamara Tchkonia, Yi Zhu, Laura J Niedernhofer, Paul D Robbins
Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage...
October 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28853863/nuclear-and-mitochondrial-dna-methylation-patterns-induced-by-valproic-acid-in-human-hepatocytes
#9
Jarno E J Wolters, Simone G J van Breda, Florian Caiment, Sandra M Claessen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further investigate VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation in nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Therefore, primary human hepatocytes (PHHs) were exposed to an incubation concentration of VPA that was shown to cause steatosis without inducing overt cytotoxicity...
September 13, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28837153/cardioprotective-effects-of-fibroblast-growth-factor-21-against-doxorubicin-induced-toxicity-via-the-sirt1-lkb1-ampk-pathway
#10
Shudong Wang, Yonggang Wang, Zhiguo Zhang, Quan Liu, Junlian Gu
Doxorubicin (DOX) is a highly effective antineoplastic anthracycline drug; however, the adverse effect of the cardiotoxicity has limited its widespread application. Fibroblast growth factor 21 (FGF21), as a well-known regulator of glucose and lipid metabolism, was recently shown to exert cardioprotective effects. The aim of this study was to investigate the possible protective effects of FGF21 against DOX-induced cardiomyopathy. We preliminarily established DOX-induced cardiotoxicity models in H9c2 cells, adult mouse cardiomyocytes, and 129S1/SyImJ mice, which clearly showed cardiac dysfunction and myocardial collagen accumulation accompanying by inflammatory, oxidative stress, and apoptotic damage...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28822346/comparative-study-of-single-combination-use-of-huang-lian-jie-du-decoction-and-berberine-on-their-protection-on-sepsis-induced-acute-liver-injury-by-nmr-metabolic-profiling
#11
Yan Lv, Junsong Wang, Dingqiao Xu, Shanting Liao, Pei Li, Qian Zhang, Minghua Yang, Lingyi Kong
Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, (1)H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28820966/reactive-oxygen-species-responsive-polymeric-nanoparticles-for-alleviating-sepsis-induced-acute-liver-injury-in-mice
#12
Gan Chen, Hongzhang Deng, Xiang Song, Mingzi Lu, Lian Zhao, Sha Xia, Guoxing You, Jingxiang Zhao, Yulong Zhang, Anjie Dong, Hong Zhou
Sepsis-associated acute liver injury contributes to the pathogenesis of multiple organ dysfunction syndrome and is associated with increased mortality. Currently, no specific therapeutics for sepsis-associated liver injury are available. With excess levels of reactive oxygen species (ROS) being implicated as key players in sepsis-induced liver injury, we hypothesize that ROS-responsive nanoparticles (NPs) formed via the self-assembly of diblock copolymers of poly(ethylene glycol) (PEG) and poly(propylene sulfide) (PPS) may function as an effective drug delivery system for alleviating sepsis-induced liver injury by preferentially releasing drug molecules at the disease site...
August 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28810615/detecting-serum-and-urine-metabolic-profile-changes-of-ccl4-liver-fibrosis-in-rats-at-12-weeks-based-on-gas-chromatography-mass-spectrometry
#13
Jiarong Gao, Xiu-Juan Qin, Hui Jiang, Jin-Feng Chen, Ting Wang, Ting Zhang, Shuang-Zhi Xu, Jun-Mei Song
Liver fibrosis is caused by liver injury induced by a number of chronic liver diseases, including schistosome infection, hepatitis infection, metabolic disease, alcoholism and cholestasis. The tissue damage occurring after injury or inflammation of the liver is a reversible lesion; however, liver fibrosis has become a worldwide problem and poses a threat to human health. The development of an effective drug for the prevention and treatment of liver fibrosis is ongoing and uses information from different occurrences of liver fibrosis...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#14
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28796242/the-triterpenoid-cddo-imidazolide-ameliorates-mouse-liver-ischemia-reperfusion-injury-through-activating-the-nrf2-ho-1-pathway-enhanced-autophagy
#15
Dongwei Xu, Lili Chen, Xiaosong Chen, Yankai Wen, Chang Yu, Jufang Yao, Hailong Wu, Xin Wang, Qiang Xia, Xiaoni Kong
Nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidants has been implicated to have protective roles in ischemia-reperfusion (I/R) injury in many animal models. However, the in vivo effects of CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole), a Nrf2 activator, in hepatic I/R injury is lacking and its exact molecular mechanisms are still not very clear. The goals of this study were to determine whether CDDO-Im can prevent liver injury induced by I/R in the mouse, and to elucidate the molecular target of drug action...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28763871/-the-function-of-aurora-a-and-its-role-in-the-development-of-liver-cancer
#16
M Li, Z G Ren
Aurora A plays a key role in cellular mitosis. It is located in the centrosome and spindle, and is mainly involved in the processes of centrosome maturation and separation, bipolar spindle assembly, and the regulation of mitotic progression. Recent studies have suggested that Aurora A is involved in tumorigenesis and tumor development through multiple mechanisms. Overexpression of Aurora A could cause abnormal centrosome amplification, aneuploidy formation, and G2/M checkpoint defects, which result in chromosome instability and imbalance between cell division and apoptosis, and eventually leads to abnormal cell proliferation...
June 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28752475/use-of-statins-in-patients-with-chronic-liver-disease-and-cirrhosis-current-views-and-prospects
#17
REVIEW
Jose Ignacio Vargas, Marco Arrese, Vijay H Shah, Juan Pablo Arab
PURPOSE OF REVIEW: The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. RECENT FINDINGS: Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients...
September 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#18
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729031/knockout-of-the-urate-oxidase-gene-provides-a-stable-mouse-model-of-hyperuricemia-associated-with-metabolic-disorders
#19
Jie Lu, Xu Hou, Xuan Yuan, Lingling Cui, Zhen Liu, Xinde Li, Lidan Ma, Xiaoyu Cheng, Ying Xin, Can Wang, Keke Zhang, Xuefeng Wang, Wei Ren, Ruixia Sun, Zhaotong Jia, Zibin Tian, Qing-Sheng Mi, Changgui Li
The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28688898/liver-biopsy-findings-in-patients-with-hematopoietic-cell-transplantation
#20
Farzan Eskandari, Daniel J Rowan, Parameswaran Hari, Jonathan Kapke, Robert Schneidewend, Catherine E Hagen, Kiyoko Oshima
Liver dysfunction is a frequent complication after hematopoietic cell transplantation. Liver biopsy has an important role for confirming the diagnosis of graft-versus-host disease (GVHD) or other liver diseases. The histological features of GVHD are not specific, and GVHD and other coexisting diseases may be present in the same biopsy, which makes the histologic interpretation of the liver biopsy more complex and challenging. The aim of the study is to improve the present diagnostic criteria. Fifty-two liver biopsies were studied...
August 2017: Human Pathology
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