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Xanthine oxidase

Manal M Alem, Abdullah M Alshehri, Peter Mb Cahusac, Matthew R Walters
Background: The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. Methods: A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF...
2018: Clinical Medicine Insights. Cardiology
MaryAnn Zhang, Daniel H Solomon, Rishi J Desai, Eun Ha Kang, Jun Liu, Tuhina Neogi, Seoyoung C Kim
Background -Hyperuricemia and gout are associated with increased risk of cardiovascular disease (CVD). Xanthine oxidase inhibitors (XOI), allopurinol and febuxostat, are the mainstay of urate lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. Methods -Using U.S. Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among gout patients aged ≥65 years. The primary outcome was a composite endpoint of hospitalization for myocardial infarction (MI) or stroke...
June 13, 2018: Circulation
Tasaduq Hussain Wani, Sreeraj Surendran, Anal Jana, Anindita Chakrabarty, Goutam Chowdhury
Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Knowing the mechanism of action of an anticancer drug is necessary to formulate a rational drug combination and select a cancer type for achieving maximum clinical efficacy. Using cell-based assays we showed that YM155 cause extensive DNA cleavage and reactive oxygen species generation...
June 13, 2018: Chemical Research in Toxicology
Lan-Zhu Li, Guo-Xiu Zhou, Jia Li, Wei Jiang, Bao-Lin Liu, Wen Zhou
Compounds containing trace elements copper or zinc are potential gout and hyperuricemia suppressant by virtue of their inhibiting effect on xanthine oxidase/xanthine dehydrogenase (XOD/XDH) and anti-inflammatory and anti-oxidative function. In this study, compounds Cu(hmy-paa)·SO4 ·H2 O (simplified as CuHP) and Zn(hmy-paa)·SO4 ·H2 O (simplified as ZnHP) are synthesized, where hmy-paa stands for 3-(4-hydroxy-3-methoxyphenyl)-N-(1H-pyrazol-3-yl)acrylamide). The ligand hmy-paa is composed of functional ferulic acid and 3-aminopyrazole...
September 2018: Journal of Trace Elements in Medicine and Biology
Toshinori Hirai, Toshimasa Itoh, Toshimi Kimura, Hirotoshi Echizen
AIM: Febuxostat is an active xanthine oxidase (XO) inhibitor that is widely used in the hyperuricemia treatment. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model for hypouricemic effects of febuxostat. METHODS: Previously, we have formulated a PK--PD model for predicting hypouricemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function, and drug dose using datasets reported in preapproval studies (Hirai T et al...
June 6, 2018: British Journal of Clinical Pharmacology
Tianqiao Yong, Shaodan Chen, Yizhen Xie, Ou Shuai, Xiangmin Li, Diling Chen, Jiyan Su, Chunwei Jiao, Yalei Liang
Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions...
2018: Frontiers in Pharmacology
Claudio Borghi, Stefano Omboni, Giorgio Reggiardo, Stefano Bacchelli, Daniela Degli Esposti, Ettore Ambrosioni
BACKGROUND: Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. OBJECTIVE: We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies...
June 5, 2018: BMC Cardiovascular Disorders
Sumito Sunagawa, Takashi Shirakura, Noboru Hokama, Chisayo Kozuka, Masato Yonamine, Toyotaka Namba, Satoko Morishima, Sawako Nakachi, Yukiko Nishi, Tomomi Ikema, Shiki Okamoto, Chieko Matsui, Naoki Hase, Mizuho Tamura, Michio Shimabukuro, Hiroaki Masuzaki
AIMS/INTRODUCTION: There is a controversy whether hyperuricemia is an independent risk for cardiometabolic diseases. Serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. On the other hand, evidence has accumulated that locally and systemically activated xanthine oxidase (XO), a rate limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS)...
June 3, 2018: Journal of Diabetes Investigation
Wei Zhang, Chun-Zhen Wu, Si-Yang Fan
Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (-) ethyl 1, 4-di-O-caffeoylquinate (1) and (-) methyl 1, 4-di-O-caffeoylquinate (2), together with 35 known compounds (3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis...
May 2018: Chinese Journal of Natural Medicines
N C N Perera, G I Godahewa, Bo-Hye Nam, Jung Youn Park, Jehee Lee
Disturbance in the balance between pro-oxidants and anti-oxidants result oxidative stress in aerobic organisms. However, oxidative stress can be inhibited by enzymatic and non-enzymatic defense mechanisms. Superoxide dismutases (SODs) are well-known scavengers of superoxide radicals, and they protect cells by detoxifying hazardous reactive oxygen species. Here, we have identified and characterized two different SODs, CuZnSOD and MnSOD, from black rockfish (RfCuZnSOD and RfMnSOD, respectively). In silico analysis revealed the well-conserved molecular structures comprising all essential properties of CuZnSOD and MnSOD...
May 30, 2018: Fish & Shellfish Immunology
Jaya Pandey, Preeti Prajapati, Anubha Srivastava, Poonam Tandon, Kirti Sinha, Alejandro P Ayala, Arvind K Bansal
Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hyperuricemia and gout caused by increased levels of uric acid in the blood (hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A...
May 22, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Anezia Kourkoulou, Alexandros A Pittis, George Diallinas
L-ascorbic acid (vitamin C) is an essential metabolite in animals and plants due to its role as an enzyme co-factor and antioxidant activity. In most eukaryotic organisms, L-ascorbate is biosynthesized enzymatically, but in several major groups, including the primate suborder Haplorhini, this ability is lost due to gene truncations in the gene coding for L-gulonolactone oxidase. Specific ascorbate transporters (SVCTs) have been characterized only in mammals and shown to be essential for life. These belong to an extensively studied transporter family, called Nucleobase-Ascorbate Transporters (NAT)...
March 22, 2018: Microbial Cell
Lhanoo Gunawardhana, Michael A Becker, Andrew Whelton, Barbara Hunt, Majin Castillo, Kenneth Saag
BACKGROUND: Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min)...
May 30, 2018: Arthritis Research & Therapy
Xiang Han, Yi-Chen Wu, Min Meng, Qing-Song Sun, Su-Min Gao, Hong Sun
Acute lung injury (ALI) is an important cause of morbidity and mortality for critically ill patients, and linarin (LR) may be a potential treatment for ALI as it reportedly has antioxidant, anti‑inflammatory and apoptotic‑regulating activity. In the present study, the authors report that saline and LR (12.5, 25 and 50 mg/kg) were applied to male C57BL/6 mice via gavage. Then, mice were intratracheally injected with either saline or lipopolysaccharide (LPS). LR‑pretreatment attenuated LPS‑induced ALI and platelet activation and reduced CD41 expression levels and neutrophil platelet aggregates...
May 30, 2018: International Journal of Molecular Medicine
Jiale Peng, Yaping Li, Yeheng Zhou, Li Zhang, Xingyong Liu, Zhili Zuo
Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases...
May 29, 2018: Journal of Receptor and Signal Transduction Research
Xiansheng Ren, Wei Ding, Xiaoyu Yang
Objective: To study the effects of astaxanthin on the apoptosis after spinal cord injury in rats. Methods: One hundred and forty-four healthy adult Sprague Dawley rats were divided into experimental group, control group, and sham group according to the random number table ( n =48). In the control group and the experimental group, the modified Allen's method was used to make the spinal cord injury model; in the sham group, only the lamina was cut without damaging the spinal cord...
May 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
Neha Kapoor, Sanjai Saxena
Targeting xanthine oxidase inhibition has been a prime strategy for exploration and development of non-purine based drugs for anti-hyperuricemic therapy. Recent studies from our laboratory have suggested that fungal endophytes from medicinal plants could play a pivotal role in exploration of novel therapeutic moieties. In the present study, 19 fungal endophytes were isolated from the medicinal plant Tinospora cordifolia and evaluated for their XO inhibitory activity. In the qualitative assay, Out of 19 fungal endophytes, 7 endophytes exhibited > 30% XO inhibition, of which isolates #1 TCSTITPLM, #53 TCSTITPLM, #105 TCSTITPLM and #83 TCSTITPLM were found to exhibit XO inhibition in the range of 38-45%...
June 2018: 3 Biotech
Fang Liu, Xiaoling Sun, Yunxia Zhang, Guoliang Zhao, Yancang Liu, Yiwu Zhang
The curative effects of monosialotetrahexosyl ganglioside (GM1) in the treatment of severe ischemic brain injury and its effects on tumor necrosis factor-α (TNF-α) and neuropathy disability score (NDS). Sixty patients with severe ischemic brain injury admitted to The First People's Hospital of Jining (Jining, China) from June 2014 to March 2016 were selected. They were randomly divided into the control group (n=30) and the experimental group (n=30). The patients in the control group were treated with routine therapy while those in the experimental group were treated with GM1...
June 2018: Experimental and Therapeutic Medicine
Tsuguru Fujii, Kazunori Yamamoto, Yutaka Banno
Translucency of the larval integument in Bombyx mori is caused by a lack of uric acid in the epidermis. Hime'nichi translucent (ohi) is a unique mutation causing intermediate translucency of the larval integument and male-specific flaccid paralysis. To determine the gene associated with the ohi mutation, the ohi locus was mapped to a 400-kb region containing 29 predicted genes. Among the genes in this region, we focused on Bombyx homolog of mammalian Gephyrin (BmGphn), which regulates molybdenum cofactor (MoCo) biosynthesis, because MoCo is indispensable for the activity of xanthine dehydrogenase (XDH), a key enzyme in uric acid biosynthesis...
May 24, 2018: Insect Biochemistry and Molecular Biology
J I Castillo-Arellano, S L Guzmán-Gutiérrez, A Ibarra-Sánchez, S Hernández-Ortega, A Nieto-Camacho, O N Medina-Campos, J Pedraza-Chaverri, R Reyes-Chilpa, C González-Espinosa
Mast cells (MCs) are important effectors in allergic reactions since they produce a number of pre-formed and de novo synthesized pro-inflammatory compounds in response to the high affinity IgE receptor (FcεRI) crosslinking. IgE/Antigen-dependent degranulation and cytokine synthesis in MCs have been recognized as relevant pharmacological targets for the control of deleterious inflammatory reactions. Despite the relevance of allergic diseases worldwide, efficient pharmacological control of mast cell degranulation has been elusive...
May 23, 2018: Biochemical Pharmacology
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