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Runalia Bahar, Kimberly A Wong, Chung H Liu, Christopher L Bowlus
Primary biliary cholangitis (PBC) is an autoimmune inflammatory liver disease of the interlobular bile ducts that can lead to cirrhosis and liver failure. Until recently, the only effective treatment was ursodeoxycholic acid (UDCA). However, up to 40% of PBC patients have an inadequate response to UDCA and may continue to have disease progression. Several models have been developed, including the UK-PBC and GLOBE scores, to assist in identifying patients who may benefit from second-line therapies, such as the farnesoid X receptor (FXR) agonist obeticholic acid (OCA)...
March 2018: Gastroenterology & Hepatology
Busisani W Lembede, Kennedy H Erlwanger, Pilani Nkomozepi, Eliton Chivandi
Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study interrogated the effects of T. sericea on linear growth, development of fatty liver disease, viscera morphometry and health of growing rats fed a 12% fructose solution (FS). Methods Thirty 21-day old male Wistar rat pups were randomly allocated to five treatments: group I - plain gelatine cubes (PGC) + plain tap water (PW), group II - 12% FS + PGC, group III - gelatine cubes containing fenofibrate (Feno) at a dose of 100 mg/kg body + FS, group IV - gelatine cubes containing the low dose (100 mg/kg body mass per day) of the T...
June 21, 2018: Journal of Complementary & Integrative Medicine
Se-Jin Kim, Channy Park, Joon No Lee, Raekil Park
Cisplatin is an alkylating agent that interferes with DNA replication and kills proliferating carcinogenic cells. Several studies have been conducted to attenuate the side effects of cisplatin; one such side effect in cancer patients undergoing cisplatin chemotherapy is ototoxicity. However, owing to a lack of understanding of the precise mechanism underlying cisplatin-induced side effects, management of cisplatin-induced ototoxicity remains unsolved. We investigated the protective effects of fenofibrate, a PPAR-α activator, on cisplatin-induced ototoxicity...
June 13, 2018: Toxicology and Applied Pharmacology
Shuzo Urata, Yukiko Uno, Yohei Kurosaki, Jiro Yasuda
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively...
June 12, 2018: Biochemical and Biophysical Research Communications
Montserrat A de la Rosa Rodriguez, Go Sugahara, Guido J E J Hooiveld, Yuji Ishida, Chise Tateno, Sander Kersten
BACKGROUND: The role of PPARα in gene regulation in mouse liver is well characterized. However, less is known about the role of PPARα in human liver. The aim of the present study was to better characterize the impact of PPARα activation on gene regulation in human liver. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analyzed by hematoxilin and eosin staining, qPCR, and transcriptomics...
June 7, 2018: BMC Genomics
Lucia Manni, Chiara Anselmi, Paolo Burighel, Margherita Martini, Fabio Gasparini
Tunicates, the sister group of vertebrates, possess a mechanoreceptor organ, the coronal organ, which is considered the best candidate to address the controversial issue of vertebrate hair cell evolution. The organ, located at the base of the oral siphon, controls the flow of seawater into the organism and can drive the "squirting" reaction, i.e., the rapid body muscle contraction used to eject dangerous particles during filtration. Coronal sensory cells are secondary mechanoreceptors and share morphological, developmental and molecular traits with vertebrate hair cells...
June 4, 2018: Integrative and Comparative Biology
R Preston Mason, Hazem Dawoud, Robert F Jacob, Samuel C R Sherratt, Tadeusz Malinski
The endothelium exerts many vasoprotective effects that are largely mediated by release of nitric oxide (NO). Endothelial dysfunction represents an early but reversible step in atherosclerosis and is characterized by a reduction in the bioavailability of NO. Previous studies have shown that eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), and statins individually improve endothelial cell function, but their effects in combination have not been tested. Through a series of in vitro experiments, this study evaluated the effects of a combined treatment of EPA and the active metabolite of atorvastatin (ATM) on endothelial cell function under conditions of oxidative stress...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Marwa M M Refaie, Rehab A Rifaai, Nagwa M Zenhom
Nearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator activated receptor alpha (PPARα) had protective effect in different models but still there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3 mg/kg/day for 4 weeks) subcutaneous injection followed by FEN (300 mg/kg/day) was given orally for 4 weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD) and malondialdehyde (MDA) levels...
June 3, 2018: Fundamental & Clinical Pharmacology
Jian-Feng Zhao, Hai-Rong Hua, Qian-Bo Cheng, Meng Guan, Jin-Hui Yang, Xiao-Ting Xi, Yan Li, Yu Geng
OBJECTIVE: This study aims to explore the possible role of fenofibrate in inhibiting choroidal neovascularization (CNV) in Brown Norway (BN) rats. METHODS: BN rats underwent binocular retinal laser photocoagulation to induce CNV. On day one, fenofibrate was injected into the vitreous cavity of rats in the control and experimental groups. Fundus fluorescein angiography (FFA), isolectin B4-FITC staining, immunofluorescence staining, qRT-PCR and western blot were performed at 1, 2, 3 and 4 weeks to observe the morphological changes of CNV and the expression of the vascular endothelial growth factor C (VEGF-C) and the vascular endothelial growth factor receptor-3 (VEGFR-3)...
May 30, 2018: Experimental Eye Research
Chris Maminakis, Arin C Whitman, Nahida Islam
We present a case of a patient with cutaneous T-cell lymphoma started on bexarotene 300 mg/m2 due to progressing disease. The patient experienced good clinical response, but unfortunately, she developed rapid and profound hypertriglyceridemia. Although hypertriglyceridemia occurs in high incidence with bexarotene therapy, management recommendations are scarce. Due to the rise in triglycerides, atorvastatin 10 mg daily was initiated in combination with fenofibrate 120 mg daily. Triglycerides continued to increase, so the patient was instructed to take atorvastatin 40 mg, fenofibrate 120 mg, and to hold bexarotene for 2 weeks...
January 2018: Case Reports in Oncology
Alexandros Kourentas, Maria Vertzoni, Vicky Barmpatsalou, Patrick Augustijns, Stefania Beato, James Butler, Rene Holm, Neils Ouwerkerk, Joerg Rosenberg, Tomokazu Tajiri, Christer Tannergren, Mira Symillides, Christos Reppas
The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil® suspension, two doses), SB705498 (weak base, tablets vs...
May 24, 2018: AAPS Journal
Leigh Goedeke, Jamie Bates, Daniel F Vatner, Rachel J Perry, Ting Wang, Ricardo Ramirez, Li Li, Matthew W Ellis, Dongyan Zhang, Kari E Wong, Carine Beysen, Gary W Cline, Adrian S Ray, Gerald I Shulman
Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ryo Kawasaki, Tsuneo Konta, Kohji Nishida
AIMS: Fenofibrate and statins reduced the risk of diabetic retinopathy (DR) related treatment in clinical trials. We aimed to determine whether lipid-lowering medication use reduce the risk of DR and its treatments in patients with type 2 diabetes using a real-world health claims database. METHODS: This was an observational analysis using a nation-wide health claims database of the Japan Medical Data Center (JMDC). Type 2 diabetes was defined by the ICD-10 codes with glucose-lowering medication use...
May 22, 2018: Diabetes, Obesity & Metabolism
Walter Masson, Emiliano Rossi, Daniel Siniawski, Juan Damonte, Ana Halsband, Ramiro Barolo, Miguel Scaramal
INTRODUCTION: The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. OBJECTIVES: The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. METHODS: A cross-sectional study was carried out using the computerised medical records of all patients>18 years of age with a blood triglyceride level≥1,000mg/dL between 1 January 2011 and 31 December 2016...
May 19, 2018: Clínica e Investigación en Arteriosclerosis
Keisuke Tachibana, Tomohiro Yuzuriha, Ryotaro Tabata, Syohei Fukuda, Takashi Maegawa, Rika Takahashi, Keiichi Tanimoto, Hirofumi Tsujino, Kazuto Nunomura, Bangzhong Lin, Yoshiharu Matsuura, Toshiya Tanaka, Takao Hamakubo, Juro Js Sakai, Tatsuhiko Kodama, Tadayuki Kobayashi, Kenji Ishimoto, Hiroyuki Miyachi, Takefumi Doi
Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. PPARα is mainly expressed in the liver, where it activates fatty acid oxidation and lipoprotein metabolism and improves plasma lipid profiles. Therefore, PPARα activators are often used to treat patients with dyslipidemia. To discover additional PPARα activators as potential compounds for use in hypolipidemic drugs, here we established human hepatoblastoma cell lines with luciferase reporter expression from the promoters containing peroxisome proliferator responsive elements (PPRE) and tetracycline-regulated expression of full-length human PPARα to quantify the effects of chemical ligands on PPARα activity...
May 15, 2018: Journal of Biological Chemistry
Jason A Harmer, Anthony C Keech, Anne-Sophie Veillard, Michael R Skilton, Gerald F Watts, David S Celermajer
AIM: Dyslipidemia in type 2 diabetes contributes to an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. The mechanisms for such benefit, however, are not yet well understood. We examined the effects of fenofibrate on carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in adults with type 2 diabetes...
May 12, 2018: Diabetes Research and Clinical Practice
Yushi Sunazuka, Keisuke Ueda, Kenjirou Higashi, Yusuke Tanaka, Kunikazu Moribe
We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing LabrafacTM lipophile WL 1349 (WL1349) or Labrafil® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm...
May 12, 2018: International Journal of Pharmaceutics
Habib Yaribeygi, Mohammad T Mohammadi, Ramin Rezaee, Amirhossein Sahebkar
Among several pathological mechanisms involved in diabetic nephropathy, oxidative stress, inflammation, and apoptosis play a prominent role. Fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, has markedly improved oxidative stress and inflammatory responses, but there is no evidence about its effects on interleukin-18 (IL-18), NADPH oxidase type 4 (NOX-4), and p53 expression in diabetic kidneys. The aim of this study was to evaluate possible effects of fenofibrate on improving the underlying mechanisms of diabetic nephropathy...
May 15, 2018: Journal of Cellular Biochemistry
Palak Galhotra, Pankaj Prabhakar, Himanshu Meghwani, Soheb A Mohammed, Sanjay Kumar Banerjee, Sandeep Seth, Milind P Hote, K H Reeta, Ruma Ray, Subir Kumar Maulik
Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats...
May 14, 2018: Molecular and Cellular Biochemistry
Xin Lian, Gang Wang, Honglan Zhou, Zongyu Zheng, Yaowen Fu, Lu Cai
Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins...
2018: Journal of Cancer
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