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Xanthine oxidase

Oleg Pak, Akylbek Sydykov, Djuro Kosanovic, Ralph T Schermuly, Alexander Dietrich, Katrin Schröder, Ralf P Brandes, Thomas Gudermann, Natascha Sommer, Norbert Weissmann
Lung ischaemia-reperfusion injury (LIRI) occurs in many lung diseases and during surgical procedures such as lung transplantation. The re-establishment of blood flow and oxygen delivery into the previously ischaemic lung exacerbates the ischaemic injury and leads to increased microvascular permeability and pulmonary vascular resistance as well as to vigorous activation of the immune response. These events initiate the irreversible damage of the lung with subsequent oedema formation that can result in systemic hypoxaemia and multi-organ failure...
2017: Advances in Experimental Medicine and Biology
Daniel Hernandez-Saavedra, Kalin Swain, Rubin Tuder, Steen V Petersen, Eva Nozik-Grayck
When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling...
2017: Advances in Experimental Medicine and Biology
Linqiang Ma, Jinbo Hu, Jiayu Li, Yi Yang, Linkun Zhang, Lingyun Zou, Rufei Gao, Chuan Peng, Yue Wang, Ting Luo, Xiaojiao Xiang, Hua Qing, Xiaoqiu Xiao, Chaodong Wu, Zhihong Wang, John Cijiang He, Qifu Li, Shumin Yang
The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor...
October 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Carine F Souza, Camila Marina Verdi, Matheus D Baldissera, Pedro Henrique Doleski, Bruno S Vizzotto, Roberto C V Santos, Bernardo Baldisserotto
Several pieces of evidence have linked the involvement of xanthine oxidase (XO), a source of uric acid and reactive oxygen species (ROS), to pro-oxidative and pro-inflammatory effects observed during bacterial fish diseases. Thus, the aim of this study was to evaluate whether upregulation of splenic XO activity contributes to disease pathogenesis of Aeromonas caviae infection, as well as whether it may be considered a pathway involved in ROS and nitric oxide (NO) production. XO activity increased in the spleen of infected animals, as did the splenic levels of uric acid, ROS and metabolites of nitric oxide (NOx), compared to the uninfected control group...
October 14, 2017: Microbial Pathogenesis
Yanjie Ma, Huimin Cao, Zhixin Li, Jinzhi Fang, Xiaomin Wei, Peng Cheng, Rui Jiao, Xiaoran Liu, Ya Li, Yun Xing, Jiali Tang, Liang Jin, Taiming Li
Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60)...
October 16, 2017: International Journal of Molecular Sciences
Jonathan Cheong, Jason S Halladay, Jasleen K Sodhi, Emile Plise, Laurent Salphati
BACKGROUND: Non-selective chemical inhibitors of phase I and phase II enzymes are commonly used in in vitro metabolic studies to elucidate the biotransformation pathways of drugs. However, the inhibition of the inhibitors on efflux and uptake transporters is not well investigated, potentially leading to unexpected and ambiguous results in these studies. OBJECTIVE: The commonly used metabolizing enzyme inhibitors, 1-aminobenzotriazole (ABT), SKF-525A, pargyline, allopurinol, menadione, methimazole, piperine and raloxifene, were examined for their potential inhibition of the major hepatic ABC (ATP binding cassette) and SLC (solute carrier) transporters...
October 10, 2017: Drug Metabolism Letters
Ting-Jian Zhang, Song-Ye Li, Lin Wang, Qi Sun, Qing-Xia Wu, Yi Zhang, Fan-Hao Meng
A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety played a significant role on the inhibition and that a benzyl ether tail (e.g., ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory potency. Among these compounds, 10q (IC50 = 0...
September 27, 2017: European Journal of Medicinal Chemistry
Nahla S El-Shenawy, Reham Z Hamza, Howayda E Khaled
The α-lipoic acid is a soft material and useful for the potential biomedical applications. The study was aimed to assess the potency of α-lipoic acid (ALA) against the toxicity of dimethylnitrosamine (DMN) on spleen of mice by assessing the antioxidants, histopathological and ultrastructure changes. The experiment was achieved on six groups of male mice as following; groups 1, 2, 3, and 4 were served as a control, ALA groups, low dose of DMN (DMN-LD; 2mgkg(-1)) and high dose of DMN (DMN-HD; 4mgkg(-1)). Group 5 was received DMN-LD plus ALA and group 6 was given DMN-HD plus ALA...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anne-Kathrin Tausche, Rieke Alten, Nicola Dalbeth, Jeff Kopicko, Maple Fung, Scott Adler, Nihar Bhakta, Chris Storgard, Scott Baumgartner, Kenneth Saag
Objective: To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study. Methods: Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data...
September 23, 2017: Rheumatology
M Cutolo, M A Cimmino, F Perez-Ruiz
OBJECTIVE: Hyperuricemia leading to urate crystal formation in tissues represents the pathophysiological mechanism of gout. Guidelines recommend a therapeutic target of serum urate concentration (sUA) <6 mg/dL, or even lower (≤5 mg/dL) in patients with large deposits. We conducted an analysis with the aim to achieve additional insights into the urate-lowering efficacy of two xanthine oxidase inhibitors, allopurinol and febuxostat. PATIENTS AND METHODS: This was a pooled analysis of phase III trials on allopurinol and febuxostat, including 4101 patients with gout and hyperuricemia...
September 2017: European Review for Medical and Pharmacological Sciences
M D Baldissera, C F Souza, P H Doleski, S G Monteiro, A S da Silva, B Baldisserotto
Adenosine deaminase (ADA) activity, through adenosine (Ado) levels, as well as xanthine oxidase (XO) activity through uric acid levels exerts an essential role on immune and inflammatory responses during infectious diseases. Thus, the aim of this study was to evaluate the involvement of seric ADA and XO activities in the inflammatory and oxidative status of silver catfish naturally infected with Ichthyophthirius multifiliis. Seric ADA activity decreased, while Ado levels increased in infected animals compared to uninfected animals...
October 13, 2017: Journal of Fish Diseases
Xin He, Chun-Yan Liu, Ji-Feng Yin, Ai-Hua Jin, Xue-Zhe Yin, Ji-Shu Quan
To study the inhibitory effect of Rhaponticum uniflorum on apoptosis induced by H2O2 in HepG2 cells. Human HepG2 cells injury models were established by H2O2, then cell survival rate was assayed by MTT method; levels of LDH, ALT, and AST were detected by chemical colorimetric method;SOD activity was detected by xanthine oxidase method; GSH content was detected by dithio-bis-nitrobenzoic acid(DTNB); MDA level was detected by thiobarbituric acid (TBA) method;and the relative activities of Caspase-3, 8 and 9 were measured by Colorimetry...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Valentin Barquissau, Frédéric Capel, Dominique Dardevet, Christine Feillet-Coudray, Anne Gallinier, Marie-Agnès Chauvin, Jennifer Rieusset, Béatrice Morio
Whereas reactive oxygen species (ROS) can have opposite impacts on insulin signaling, they have mainly been associated with mitochondrial dysfunction in skeletal muscle. We analyzed the relationship between these three features in skeletal muscle of senescence accelerated mice (SAM) prone (P8), which are characterized by enhanced oxidative stress compared to SAM resistant (R1). Oxidative stress, ROS production, antioxidant system, mitochondrial content and functioning, as well as in vitro and in vivo insulin signaling were investigated in gastrocnemius and quadriceps muscles...
October 9, 2017: Free Radical Biology & Medicine
Qingyong Li, Xiaoyan Kang, Chuanchao Shi, Yujuan Li, Kaustav Majumder, Zhengxiang Ning, Jiaoyan Ren
In this study, walnut meal hydrolysates (WMH) and dephenolized walnut meal hydrolysates (DWMH) were found to effectively decrease the serum uric acid level and protect the renal function in potassium oxonate-induced hyperuricemic rats in vivo as well as inhibit xanthine oxidase in vitro. Two novel antihyperuricemic peptides including WPPKN (640.8 Da) and ADIYTE (710.7 Da) were purified from DWMH via Sephadex G-15 gel filtration and reverse-phase high-performance liquid chromatography and identified by LC-ESI-MS/MS...
October 11, 2017: Food & Function
Alexander T Chen, Theodore Malmstrom, Henry A Nasrallah
BACKGROUND: Allopurinol is a xanthine oxidase inhibitor commonly used in the treatment of gout. Recent studies have also shown its promise as an adjunctive treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms involving the purinergic pathway. However, its efficacy across studies has been inconsistent, so we conducted a meta-analysis of the published controlled studies with the goal of determining the efficacy profile of allopurinol as an adjunctive treatment for mania in bipolar disorder...
September 30, 2017: Journal of Affective Disorders
Sadaf Sultan, Uzma Ashiq, Rifat Ara Jamal, Mohammad Mahroof-Tahir, Zara Shaikh, Bushra Shamshad, Mehreen Lateef, Lubna Iqbal
The present study explores the synthesis and inhibitory potential of vanadium(V) complexes of hydrazides (1c-12c) against oxidative enzymes including xanthine oxidase and lipoxygenase (LOX). In addition, non-enzymatic radical scavenging activities of these complexes were also determined. On the basis of spectral, elemental and physical data, synthesized vanadium(V) complexes are tentatively assigned to have an octahedral geometry with two hydrazide ligands and two oxo groups forming a negatively charged sphere complex with ammonium as counter ion...
October 9, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Mohammad Javad Alemzadeh-Ansari, Seyed Kianoosh Hosseini, Azita Hajhossein Talasaz, Mohammad Mohammadi, Masumeh Lotfi Tokaldani, Arash Jalali, Hamidreza Pourhosseini
BACKGROUND: Increased accumulation of reactive oxygen species contributes to pathophysiologic states such as endothelial dysfunction, metabolic and functional impairment, inflammatory activation, and other features of cardiovascular pathophysiology. Allopurinol acts as a xanthine oxidase inhibitor that reduces the amount of free radicals after reactive oxygen species generation. METHODS AND RESULTS: In this placebo-controlled randomized clinical trial, all patients admitted with coronary artery disease who are candidates for elective percutaneous coronary intervention (PCI) were included...
September 27, 2017: American Journal of Therapeutics
Ovender Singh, Nidhi Tyagi, Marilyn M Olmstead, Kaushik Ghosh
Bio-inspired manganese [Mn(N5Py)(H2O)(CH3OH)](ClO4)2 (1) and iron [Fe(N5Py)(H2O)(ClO4)]ClO4 (2) complexes derived from a pentadentate ligand (N5Py = 2,6-bis((E)-1-phenyl-2-(pyridin-2-ylmethylene)hydrazinyl)pyridine) framework containing a N5 binding motif were synthesized and characterized using different spectroscopic methods. The molecular structures of complexes 1 and 2 were determined by X-ray crystallography. These complexes were found to be stable under physiological conditions and exhibited an excellent superoxide dismutase (SOD) activity...
October 6, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Temidayo Olutayo Omóbòwálé, Ademola Adetokunbo Oyagbemi, Bukola Ayokunmi Alaba, Olufunke Eunice Ola-Davies, Olumuyiwa Abiola Adejumobi, Ebunoluwa Racheal Asenuga, Temitayo Olabisi Ajibade, Adeolu Alex Adedapo, Momoh Audu Yakubu
BACKGROUND: Toxicities due to fluoride exposure from natural and industrial sources occur commonly in man and animals with severe consequences ranging from mild cardiac derangements to sudden death. In this study, we investigated the protective effects of the methanol extract of Azadirachta indica (AI) against sodium fluoride (NaF)-induced hypertension and genotoxicity in rats. METHODS: Sixty rats were divided into six groups of ten rats each as follows: Group A, the control group received distilled water; Group B rats were administered NaF at 600 ppm in drinking water; Groups C and D rats were pre-treated with the methanol extract of AI and thereafter administered NaF at 600 ppm in drinking water for 7 consecutive days; Groups E and F rats were co-administered with AI and NaF...
October 5, 2017: Journal of Basic and Clinical Physiology and Pharmacology
Emily Huneycutt, Chase Board, Jennifer N Clements
OBJECTIVE: To review the pharmacokinetics, clinical efficacy, safety, and role of lesinurad for the management of hyperuricemia associated with gout. DATA SELECTION: A MEDLINE search (2000 to April 2017) was conducted using the terms hyperuricemia, gout, URAT-1, URAT-1 transporter, and lesinurad. Published articles and scientific posters relevant to the efficacy and safety of lesinurad were reviewed and summarized. DATA SYNTHESIS: Lesinurad was evaluated in 3 randomized, phase 3 clinical trials (CRYSTAL, CLEAR 1 and 2)...
January 1, 2017: Journal of Pharmacy Practice
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