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Statins and liver

Chandrakala Aluganti Narasimhulu, Kathryn Young Burge, Mitsushita Doomra, Aladdin Riad, Sampath Parthasarathy
Pharmacological intervention using statins and PCSK9 inhibitors have become first-line therapy in the prevention of hypercholesterolemia and atherosclerosis. Currently, no agent is available for the primary prevention of atherosclerosis. However, there is an emerging hypothesis that atherosclerosis could be driven by inflammation. In this study, we tested whether pretreatment with an aqueous extract from sesame oil (SOAE), which showed potent anti-inflammatory properties without hypocholesterolemic actions, would prevent subsequent atherosclerosis development in a mouse model...
August 16, 2018: Scientific Reports
Sterling Farrer
Coronary heart disease continues to be the leading cause of death in the United States. Current attempts to treat atherosclerosis and coronary artery disease often involve pharmaceutical and surgical treatments. While these treatments are successful in managing the pain from coronary heart disease, they do little to prevent or stop it. There are a number of clinical strategies that are currently being researched to treat atherosclerosis through HDL-increasing therapies. These clinical studies have shown positive effects through nutritional intervention, exercise, stress reduction, and tobacco and alcohol cessation...
2018: Advances in Preventive Medicine
Elisa Pose, Jonel Trebicka, Rajeshwar P Mookerjee, Paolo Angeli, Pere Ginès
In addition to their effects in lowering cholesterol levels, statins have pleiotropic effects, particularly anti-inflammatory, antiangiogenic, and antifibrotic, that may be beneficial in some chronic inflammatory conditions. The effects of statins as potential treatment in chronic liver diseases have not been investigated until very recently due to concerns related to their safety in patients with liver impairment. A number of experimental studies in animal models of liver diseases have shown that statins decrease hepatic inflammation, fibrogenesis and portal pressure...
July 31, 2018: Journal of Hepatology
Ya-Wen Lu, Ying-Chao Zhu, Li Zhang, Ping Li, Jie Yang, Xiao-Dong Wen
Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China...
June 2018: Chinese Journal of Natural Medicines
Mauro Bernardi, Paolo Caraceni
The current approaches to the management of patients with decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. The improved knowledge of the pathophysiological background of advanced cirrhosis, represented by a sustained systemic inflammation strictly linked to a circulatory dysfunction, provides a novel paradigm for the management of these patients, with the ambitious target of modifying the course of the disease by preventing the onset of complications and multiorgan failure; these interventions will eventually improve patients' quality of life, prolong survival and reduce health-care costs...
July 19, 2018: Nature Reviews. Gastroenterology & Hepatology
Dave Tang, Michaela Fakiola, Genevieve Syn, Denise Anderson, Heather J Cordell, Elizabeth S H Scaman, Elizabeth Davis, Simon J Miles, Toby McLeay, Sarra E Jamieson, Timo Lassmann, Jenefer M Blackwell
Chronic renal disease (CRD) associated with cardiovascular disease (CVD) and/or type 2 diabetes (T2D) is a significant problem in Aboriginal Australians. Whole exome sequencing data (N = 72) showed enrichment for ClinVar pathogenic variants in gene sets/pathways linking lipoprotein, lipid and glucose metabolism. The top Ingenuity Pathway Analysis canonical pathways were Farsenoid X Receptor and Retinoid Receptor (FXR/RXR; (P = 1.86 × 10-7 ), Liver X Receptor and Retinoid Receptor (LXR/RXR; P = 2...
July 19, 2018: Scientific Reports
Slobodan M Janković, Danka Tešić, Jelena Anđelković, Marina Kostić
Evolocumab is fully human monoclonal antibody which binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), and prevents its blocking effect on recycling of liver low-density lipoprotein (LDL) receptors. Areas covered: The aim of this review is to assess efficacy, safety, and cost-effectiveness of evolocumab in adult patients with high cardiovascular risk. Major research databases MEDLINE, EBSCO, and CENTRAL were systematically searched for relevant study reports. Expert commentary: Even when given in full doses, statins augmented with ezetimibe and cholesterol-binding resins could not reduce cholesterol baseline level for more than 66%, while evolocumab reduces cholesterol level for 75% or even more...
July 25, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
Meredith A Sigler, Lee Congdon, Krystal L Edwards
Background: Nonalcoholic fatty liver disease (NAFLD) is a common complication in patients with metabolic syndrome. The role of statin therapy specifically for the treatment of NAFLD remains unknown. The aim of this review is to discuss outcomes of recent articles analyzing statin therapy in patients with NAFLD. Findings: A total of 12 trials met the inclusion criteria. Statins were not found to increase the prevalence of NAFLD once confounding variables were considered...
2018: Clinical Medicine Insights. Gastroenterology
Jessica Warns, Gurdeep Marwarha, Natalie Freking, Othman Ghribi
Colorectal cancer (CRC) is the third most diagnosed cancer in the western world, affecting 1 out of approximately 22 people in their lifetime. Several epidemiological studies suggest a positive association between high plasma cholesterol levels and colorectal cancer. However, the molecular mechanisms by which cholesterol may alter the risk of colorectal cancer (CRC) are ill-defined as the cholesterol lowering drugs statins do not appear to decrease a patient's risk of developing colorectal cancer. Cholesterol is metabolized to active derivatives including cholesterol oxidization products (COP), known as oxysterols, which have been shown to alter cellular proliferation...
July 24, 2018: Biochimie
Mu-Yi Yang, Zhen-Yu Diao, Zhi-Yin Wang, Gui-Jun Yan, Guang-Feng Zhao, Ming-Ming Zheng, An-Yi Dai, Yi-Min Dai, Ya-Li Hu
Preeclampsia is associated with over-activation of the innate immune system in the placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With their potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of preeclampsia, although evidence remains inadequate. Herewith, we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide (LPS)-induced rat preeclampsia model, through targeting the TLR4/NF-κB pathway...
July 23, 2018: Journal of Biomedical Research
Ana C Marques, Estela N B Busanello, Diogo N de Oliveira, Rodrigo R Catharino, Helena C F Oliveira, Anibal E Vercesi
Statins are the preferred therapy to treat hypercholesterolemia. Their main action consists of inhibiting the cholesterol biosynthesis pathway. Previous studies report mitochondrial oxidative stress and membrane permeability transition (MPT) of several experimental models submitted to diverse statins treatments. The aim of the present study was to investigate whether chronic treatment with the hydrophilic pravastatin induces hepatotoxicity in LDL receptor knockout mice ( LDLr -/- ), a model for human familial hypercholesterolemia...
2018: Frontiers in Pharmacology
Linda Saxe Einbond, Morando Soffritti, Davide Degli Esposti, Hsan-Au Wu, Michael Balick, Hongbao Ma, Stephen Redenti, Alan Roter
Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of black cohosh and actein on rat liver tissue, using Ingenuity and ToxFX analyses. Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) for 24 h or actein for 6 and 24 h, at 35.7 mg/kg, and liver tissue collected for gene expression analysis...
June 30, 2018: Food and Chemical Toxicology
Meir Mizrahi, Tomer Adar, Gadi Lalazar, Dean Nachman, Madi El Haj, Ami Ben Ya'acov, Yoav Lichtenstein, Yehudit Shabat, Dimitri Kanovich, Lida Zolotarov, Yaron Ilan
Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are common causes of drug-induced liver injury (DILI). This study aimed to determine the ability to reduce APAP- and statins-mediated liver injury by using formulations that combine glycosphingolipids and vitamin E. Methods: Mice were injected with APAP or with statins and treated before and after with β-glucosylceramide (GC), with or without vitamin E. Mice were followed for changes in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase 3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine levels by flow cytometry...
June 28, 2018: Journal of Clinical and Translational Hepatology
Nicole K Zagelbaum, Srikanth Yandrapalli, Christopher Nabors, William H Frishman
Bempedoic acid (ETC-1002) is a new agent that reduces cholesterol synthesis through inhibition of adenosine triphosphate citrate lyase (ACL), an enzyme upstream from 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA). In animal models, bempedoic acid also influences fatty acid synthesis but in humans its role is limited primarily to lowering low-density lipoprotein cholesterol (LDL-C). In early clinical trials, bempedoic acid has been well tolerated and without major side effects. Alone or in various combinations with Atorvastatin and/or Ezetimibe, LDL-C lowering has ranged from 17% to 64%...
June 22, 2018: Cardiology in Review
Agnetha de Sá, David A Hart, Karim Khan, Alexander Scott
INTRODUCTION: Statins are widely used to inhibit cholesterol production in the liver among people with hypercholesterolemia. A recent epidemiological study in the UK has shown that statin use (unlike elevated BMI) is not associated with an increased risk of Achilles tendon rupture. However, because of laboratory reports suggesting a negative influence of statins on tenocyte metabolism, we decided to directly compare the Achilles tendon structure (cross-sectional area and longitudinal collagen organization) in regular statin users compared to non-users...
2018: PloS One
Hao Li, Ming-Hui Chen, Joseph G Ibrahim, Sungduk Kim, Arvind K Shah, Jianxin Lin, Andrew M Tershakovec
Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs...
April 18, 2018: Biostatistics
Vanessa El Kamari, Corrilynn O Hileman, Pierre M Gholam, Manjusha Kulkarni, Nicholas Funderburg, Grace A McComsey
BACKGROUND & AIMS: Therapies are needed to limit progression of fatty liver diseases in patients with HIV infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults. METHODS: We performed secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 years; body mass index, 29 kg/m2 ; HIV1 RNA<1000 copies/mL; LDL-cholesterol <130 mg/dL) receiving antiretroviral therapy...
June 13, 2018: Clinical Gastroenterology and Hepatology
Nikola Hadzi-Petrushev, Katerina Dimovska, Nikola Jankulovski, Dine Mitrov, Mitko Mladenov
Oxidative stress and inflammation contribute to the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD), and the control of lipid status by statins may help to stop the progression of NAFLD. We hypothesized that the addition of antioxidant vitamins C and E to atorvastatin therapy is associated with improved serum enzyme antioxidant status. NAFLD-related serum parameters and the activity of antioxidant enzymes, before and after 3 months of treatment, were determined in patients receiving atorvastatin alone or atorvastatin plus antioxidants...
2018: Advances in Pharmacological Sciences
Vasilios G Athyros, Niki Katsiki, Dimitri P Mikhailidis
No abstract text is available yet for this article.
June 8, 2018: Cardiovascular Therapeutics
Maka S Hedrington, Stephen N Davis
Drug-induced hepatic injury is the most common cause of acute liver failure in the United States. Peroxisome proliferator-activated receptor alpha (PPARα)-mediated drugs are included among the approximately 900 natural and synthetic substances, which have shown hepatotoxicity. Areas covered: This review will focus on fibrates - PPARα agonists and their implication in causing liver injury. Expert opinion: Compelling evidence for fibrate-induced hepatotoxicity is not available. Results have been varying because several large randomized clinical trials have reported similar elevations of plasma transaminase levels in fibrate or placebo treated groups...
July 2018: Expert Opinion on Drug Metabolism & Toxicology
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