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https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#1
Danjun Song, Min Luo, Manyun Dai, Shizhong Bu, Weihua Wang, Burong Zhang, Frank J Gonzalez, Aiming Liu
While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27915128/cholesterol-reducing-agents-inhibit-assembly-of-type-i-parainfluenza-viruses
#2
Shringkhala Bajimaya, Tsuyoshi Hayashi, Tünde Frankl, Peter Bryk, Brian Ward, Toru Takimoto
Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV...
December 1, 2016: Virology
https://www.readbyqxmd.com/read/27909849/monitoring-contaminants-of-emerging-concern-from-tertiary-wastewater-treatment-plants-using-passive-sampling-modelled-with-performance-reference-compounds
#3
Tamanna Sultana, Craig Murray, M Ehsanul Hoque, Chris D Metcalfe
The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal...
December 2016: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27888753/gastrointestinal-bleeding-and-intracranial-hemorrhage-in-concomitant-users-of-warfarin-and-antihyperlipidemics
#4
Charles E Leonard, Colleen M Brensinger, Warren B Bilker, Stephen E Kimmel, Xu Han, Young Hee Nam, Joshua J Gagne, Margaret J Mangaali, Sean Hennessy
BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27867278/effect-of-methanolic-leaf-extract-of-talinum-triangulare-jacq-willd-on-biochemical-parameters-in-diet-induced-dyslipidemia-wistar-rats
#5
Olubukola Sinbad Olorunnisola, Adewale Adetutu, Anthony Jide Afolayan, Abiodun Olusoji Owoade
OBJECTIVE: To investigate the effect of methanolic leaf extract of Talinum triangulare on hematological parameters, enzymatic and non-enzymatic antioxidant status, and serum lipid in Wistar rats fed standard laboratory, or 2% cholesterol-enrich diet. MATERIAL AND METHODS: Wistar rats (180-210g) divided into six groups of six animals (males) each were fed 2% cholesterol-enriched diet and orally treated with 0.9% saline or extract of Talinum triangulare (250, 500, and 1000 mg/kg per body weight) daily for eight weeks...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27858342/physiologically-based-pharmacokinetic-pbpk-modeling-of-pitavastatin-and-atorvastatin-to-predict-drug-drug-interactions-ddis
#6
Peng Duan, Ping Zhao, Lei Zhang
BACKGROUND: The disposition of statins varies and involves both metabolizing enzymes and transporters, making predictions of statin drug-drug interactions (DDIs) challenging. Physiologically based pharmacokinetic (PBPK) models have, however, demonstrated ability to predict complex DDIs. OBJECTIVE: In this study, PBPK models of two statins (pitavastatin and atorvastatin) were developed and applied to predict pitavastatin and atorvastatin associated DDIs. METHOD: Pitavastatin and atorvastatin PBPK models were developed using in vitro and human pharmacokinetic data in a population-based PBPK software (SimCYP(®)) by considering the contribution of both metabolizing enzymes and transporters to their overall pharmacokinetics...
November 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27836351/characterizing-pharmaceutical-personal-care-product-and-hormone-contamination-in-a-karst-aquifer-of-southwestern-illinois-usa-using-water-quality-and-stream-flow-parameters
#7
L K Dodgen, W R Kelly, S V Panno, S J Taylor, D L Armstrong, K N Wiles, Y Zhang, W Zheng
Karst aquifers are drinking water sources for 25% of the global population. However, the unique geology of karst areas facilitates rapid transfer of surficial chemicals to groundwater, potentially contaminating drinking water. Contamination of karst aquifers by nitrate, chloride, and bacteria have been previously observed, but little knowledge is available on the presence of contaminants of emerging concern (CECs), such as pharmaceuticals. Over a 17-month period, 58 water samples were collected from 13 sites in the Salem Plateau, a karst region in southwestern Illinois, United States...
November 8, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27835930/master-autophagy-regulator-transcription-factor-eb-tfeb-regulates-cigarette-smoke-induced-autophagy-impairment-and-copd-emphysema-pathogenesis
#8
Manish Bodas, Neel Patel, David Silverberg, Kyla Walworth, Neeraj Vij
AIMS: Recent studies have shown that cigarette smoke (CS)-induced oxidative-stress impairs autophagy resulting in aggresome-formation that correlates with the severity of COPD-emphysema. Although, specific step in autophagy-pathway that is impaired is unknown. Hence, in this study we aimed to evaluate the role of master autophagy-regulator and transcription factor-EB (TFEB) in CS-induced COPD-emphysema pathogenesis. RESULTS: We first observed that TFEB-accumulates in the peri-nuclear spaces of the COPD lung tissues of tobacco-smokers and severe-emphysema subjects...
November 11, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27835067/effect-of-the-lipid-regulator-gemfibrozil-in-the-cladocera-daphnia-magna-at-different-temperatures
#9
Beatriz Salesa, María D Ferrando, María J Villarroel, Encarna Sancho
In the present study, an ecotoxicological approach to the evaluation of Gemfibrozil (GEM) as an emerging organic pollutant was done. In order to assess its toxicity, tests were conducted using the cladocera Daphnia magna. Experiments were carried out at 22°C and 28°C. EC50, feeding behavior, and chronic toxicity tests (21 days) were evaluated in D. magna exposed to GEM as well as cholesterol levels at 21-day chronic exposure. D. magna GEM EC50 values (24 h) in our experimental conditions were 148.75 and 116...
November 11, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27686305/pioglitazone-improves-serum-lipid-profile-in-diet-induced-hyperlipidaemic-non-diabetic-rats
#10
Mazhar Hussian, Abdul Qudoos Arain, Sadia Chiragh
OBJECTIVE: To evaluate the anti-dyslipidaemic effects of pioglitazone in diet-induced non-diabetic hyperlipidaemic rats and to compare them with gemfibrozil. METHODS: This comparative animal study was conducted at the Postgraduate Medical Institute, Lahore, Pakistan, from July to September 2011, and comprised Sprague Dawley albino rats divided into three equal groups. Initially all three groups were given high-lipid diet containing cholesterol 1.5g, coconut oil 8ml and sodium cholate 1...
October 2016: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/27665778/transcriptome-analyses-demonstrate-that-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-activity-of-an-ultraviolet-absorber-2-2-hydroxy-3-5-di-tert-butylphenyl-benzotriazole-as-possible-mechanism-of-their-toxicity-and-the-gender-differences
#11
Mutsuko Hirata-Koizumi, Ryota Ise, Hirohito Kato, Takashi Matsuyama, Tomoko Nishimaki-Mogami, Mika Takahashi, Atsushi Ono, Makoto Ema, Akihiko Hirose
2-(2'-Hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), the Benzotriazole UV-stabilizer (BUVSs) known as UV-320, is widely used in plastic materials for protection against UV-irradiation. Previously, we reported that oral ingestion of HDBB induce hepatotoxicity including hepatocyte hypertrophy and necrosis in rats and, males was more susceptible compared with females in young rats while no sex-related difference was observed in preweaning rats. Phenotypes observed in our previous study imply involvement of peroxisome proliferator-activated receptor (PPAR) α in HDBB hepatotoxicity, however, direct evidence that HDBB can activate PPARα has not been provided and the mechanism which underlying the gender difference of HDBB hepatotoxicity was not clearly elucidated...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27648490/transporter-mediated-hepatic-uptake-plays-an-important-role-in-the-pharmacokinetics-and-drug-drug-interactions-of-montelukast
#12
M V Varma, E Kimoto, R Scialis, Y Bi, J Lin, H Eng, A S Kalgutkar, A F El-Kattan, A D Rodrigues, L M Tremaine
Montelukast, a leukotriene receptor antagonist commonly prescribed for treatment of asthma, is primarily metabolized by Cytochrome P450 (CYP)2C8, and has been suggested as a probe substrate for investigating CYP2C8 activity in vivo. We evaluated the quantitative role of hepatic uptake transport in its pharmacokinetics and drug-drug interactions (DDIs). Montelukast was characterized with significant active uptake in human hepatocytes, and showed affinity towards organic anion transporting polypeptides (OATPs) in transfected cell systems...
September 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27642087/quantitative-prediction-of-drug-drug-interactions-involving-inhibitory-metabolites-in-drug-development-how-can-physiologically-based-pharmacokinetic-modeling-help
#13
I E Templeton, Y Chen, J Mao, J Lin, H Yu, S Peters, M Shebley, M V Varma
This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug-drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent-metabolite pairs is described and guidance on strategic application is provided...
September 19, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27624558/the-enhanced-atorvastatin-hepatotoxicity-in-diabetic-rats-was-partly-attributed-to-the-upregulated-hepatic-cyp3a-and-slco1b1
#14
Nan Shu, Mengyue Hu, Zhaoli Ling, Peihua Liu, Fan Wang, Ping Xu, Zeyu Zhong, Binbin Sun, Mian Zhang, Feng Li, Qiushi Xie, Xiaodong Liu, Li Liu
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27553001/phytotoxicity-of-15-common-pharmaceuticals-on-the-germination-of-lactuca-sativa-and-photosynthesis-of-chlamydomonas-reinhardtii
#15
Ma Rosa Pino, Selene Muñiz, Jonatan Val, Enrique Navarro
Pharmaceuticals reach terrestrial environments through the application of treated wastewaters and biosolids to agricultural soils. We have investigated the toxicity of 15 common pharmaceuticals, classified as nonsteroidal anti-inflammatory drugs (NSAIDs), blood lipid-lowering agents, β-blockers and antibiotics, in two photosynthetic organisms. Twelve pharmaceuticals caused inhibitory effects on the radicle and hypocotyl elongation of Lactuca sativa seeds. The EC50 values obtained were in the range of 170-5656 mg L(-1) in the case of the radicle and 188-4558 mg L(-1) for the hypocotyl...
August 24, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27548563/role-of-gemfibrozil-as-an-inhibitor-of-cyp2c8-and-membrane-transporters
#16
Aleksi Tornio, Pertti J Neuvonen, Mikko Niemi, Janne T Backman
INTRODUCTION: Cytochrome P450 (CYP) 2C8 is a drug metabolizing enzyme of major importance. The lipid-lowering drug gemfibrozil has been identified as a strong inhibitor of CYP2C8 in vivo. This effect is due to mechanism-based inhibition of CYP2C8 by gemfibrozil 1-O-β-glucuronide. In vivo, gemfibrozil is a fairly selective CYP2C8 inhibitor, which lacks significant inhibitory effect on other CYP enzymes. Gemfibrozil can, however, have a smaller but clinically meaningful inhibitory effect on membrane transporters, such as organic anion transporting polypeptide 1B1 and organic anion transporter 3...
August 22, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27479466/modeling-of-pharmaceuticals-mixtures-toxicity-with-deviation-ratio-and-best-fit-functions-models
#17
Monika Wieczerzak, Błażej Kudłak, Galina Yotova, Miroslava Nedyalkova, Stefan Tsakovski, Vasil Simeonov, Jacek Namieśnik
The present study deals with assessment of ecotoxicological parameters of 9 drugs (diclofenac (sodium salt), oxytetracycline hydrochloride, fluoxetine hydrochloride, chloramphenicol, ketoprofen, progesterone, estrone, androstenedione and gemfibrozil), present in the environmental compartments at specific concentration levels, and their mutual combinations by couples against Microtox® and XenoScreen YES/YAS® bioassays. As the quantitative assessment of ecotoxicity of drug mixtures is an complex and sophisticated topic in the present study we have used two major approaches to gain specific information on the mutual impact of two separate drugs present in a mixture...
November 15, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27476274/coronary-effect-of-fibrates-on-proteins-and-enzymes-which-hydrolyze-triacylglycerols
#18
REVIEW
Renata Francik, Jadwiga Kryczyk, Sławomir Francik
Clofibric acid derivatives called fibrates, are quite commonly used lipid-lowering drugs, so it is necessary to know beneficial and adverse effects of these compounds on the body. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that benefits of four fibrates such as: bezafibrate, ciprofibrate, fenofibrate and gemfibrozil continue outweigh their risk in treatment of people with blood lipid disorders. According to recommendations of the CHMP fibrates should not be used as first-line drugs, except in patients with severe hypertriglyceridemia and patients who cannot use statins...
May 2016: Acta Poloniae Pharmaceutica
https://www.readbyqxmd.com/read/27474849/evaluation-of-gemfibrozil-effects-on-a-marine-fish-sparus-aurata-combining-gene-expression-with-conventional-endocrine-and-biochemical-endpoints
#19
M Teles, C Fierro-Castro, P Na-Phatthalung, A Tvarijonaviciute, A M V M Soares, L Tort, M Oliveira
The information on the potential hazardous effects of gemfibrozil (GEM) on marine fish is extremely scarce. In the current study, molecular, endocrine and biochemical parameters were assessed in Sparus aurata after 96h waterborne exposure to a GEM concentration range. Hepatic mRNA levels of target genes known to be regulated via peroxisome proliferator-activated receptor α (pparα) in mammals, such as apolipoprotein AI (apoa1) and lipoprotein (lpl) were significantly increased, without a concomitant activation of the ppar pathways...
November 15, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27462272/activation-of-sterol-regulatory-element-binding-factors-by-fenofibrate-and-gemfibrozil-stimulates-myelination-in-zebrafish
#20
Yoshifumi Ashikawa, Yuhei Nishimura, Shiko Okabe, Shota Sasagawa, Soichiro Murakami, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Toshio Tanaka
Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs)...
2016: Frontiers in Pharmacology
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