Search results for "allopurinol"
showing 10 items of 57 documents
Redox regulation of E3 ubiquitin ligases and their role in skeletal muscle atrophy
2015
Muscle atrophy is linked to reactive oxygen species (ROS) production during hindlimb-unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of our study was to determine the mechanism by which ROS cause muscle atrophy and its possible prevention by allopurinol, a well-known inhibitor of XO widely used in clinical practice, and indomethacin, a nonsteroidal anti-inflammatory drug. We studied the activation of p38 MAP Kinase and NF-?B pathways, and the expression of two E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFb) and Muscle RING Finger-1 (MuRF-1). Male Wistar rats (3 mold) conditioned by 14 days of hindlimb unloading (n=18),…
Induction of mitochondrial xanthine oxidase activity during apoptosis in the rat mammary gland
2006
Oxidative stress is an important signal for apoptosis to start. So far the mitochondrial respiratory chain has been considered as the major, if not the only, cause of such stress. Here we report that this is not the case. Xanthine oxidase, a O2(-) and H2O2 generating enzyme which is important in causing significant oxidative stress in the cytosol, is also present in the mitochondrial fraction of rat mammary gland. After weaning, during the involution of the mammary gland, massive apoptosis occurs. Mitochondrial xanthine oxidase activity increases and high mitochondrial H2O2 production takes place. Inhibition of xanthine oxidase activity by allopurinol, a specific inhibitor of xanthine oxida…
Preparation of ferulic acid derivatives and evaluation of their xanthine oxidase inhibition activity.
2007
Several ferulic acid ethyl esters (3a-h) were synthesized under the Knoevengel reaction condition and they were further reduced to afford the respective allylic alcohol derivatives (4a-g). Some of them were evaluated for the xanthine oxidase (XO) inhibitory activity. Among them, 3h exhibited a significant inhibitory activity with an IC50 value of 1.35 x 10(-5) M, while the IC50 value of allopurinol used as the positive control was 1.49 x 10(-5) M. The study suggested that the higher acidity of the phenolic OH group in the ferulic acid derivatives might result in improved XO inhibitory activity.
Sildenafil protects epithelial cell through the inhibition of xanthine oxidase and the impairment of ROS production
2009
Recent reports suggest that xanthine oxidase (XO), a modified form of the native xanthine dehydrogenase enzyme, plays an important role in various forms of ischemic and vascular injuries, inflammatory diseases, and chronic heart failure. The XO inhibitors allopurinol and its oxidation product oxypurinol held considerable promises in the treatment of these conditions both in experimental animals and in human clinical trials. More recently, an endothelium-based protective effect of sildenafil, a well-known type-5 phosphodiesterase inhibitor, has been reported in preconditioning prior to ischemia/reperfusion in healthy human subjects. Based on the structural similarities between allopurinol an…
Xanthine oxidase catalyzes the synthesis of retinoic acid
2001
Milk xanthine oxidase (xanthine: oxygen oxidoreductase; XO; EC 1.1.3.22) was found to catalyze the conversion of retinaldehyde to retinoic acid. The ability of XO to synthesize all trans-retinoic acid efficiently was assessed by its turnover number of 31.56 min-1, determined at pH 7.0 with 1 nM XO and all trans-retinaldehyde varying between 0.05 to 2 microM. The determination of both retinoid and purine content in milk was also considered in order to correlate their concentrations with kinetic parameters of retinaldehyde oxidase activity. The velocity of the reaction was dependent on the isomeric form of the substrate, the all trans- and 9-cis-forms being the preferred substrates rather tha…
Exercise as an antioxidant: it up-regulates important enzymes for cell adaptations to exercise
2006
Abstract Aims. – To assess the role of the reactive oxygen species (ROS) in cell signalling and in the regulation of gene expression. Methods. – Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. We have tested this hypothesis by studying the effect of inhibition of ROS production by allopurinol (an inhibitor of xanthine oxidase, a free radical generating enzyme) on cell signalling pathways in marathon runners and in rats submitted to exhaustive exercise by running on a treadmill. Results. – Exercise caused an activation of NF-κB in lymphocytes from marathon runners which wa…
Prolactin supplementation to culture medium improves beta-cell survival
2010
OBJECTIVES.: Recent studies demonstrated that prolactin (PRL) has beneficial effects on β cells for islet transplantation. We examined the effect of human recombinant PRL (rhPRL) supplementation to the culture media to determine its potential use in the context of clinical islet transplantation. MATERIALS AND METHODS.: Each human islet isolated from 14 deceased multiorgan donors was cultured in Miami modified media-1 supplemented with or without rhPRL (500 μg/L) for 48 hr. β-Cell survival and proliferation (BrdU and Ki-67) were determined by laser scanning cytometry. The cytoprotective effects of rhPRL against noxious stimuli were assessed by flow cytometry (tetramethylrhodamine ethyl ester…
Pancreatic islets from non-heart beating donor pig: Two-layer preservation method in an in vitro porcine model
2011
Purpose Pancreata from non-heart beating donors could represent an unlimited source of islets if their cell viability can be efficiently preserved during the time necessary to process the organs by the use of a better solution of preservation compared to the classic University of Wisconsin solution. The aim of this study was to determine whether it is possible to obtain functioning “alive islets” from non-heart-beating donors by comparing, on a porcine model, the classic “UW ice-store” method with a two-layer cold storage method (TLM) using oxygenated Perfluorocarbons (PFC) and UW. Methods Whole pancreata were harvested from 20 NHBDs female pigs with similar characteristics and preserved fo…
Ischemic type biliary lesions in histidine-tryptophan-ketoglutarate (HTK) preserved liver grafts.
2006
Ischemic type biliary lesions lead to considerable morbidity following orthotopic liver transplantation. The exact pathogenesis is unknown. One major hypothesis is that insufficient perfusion of the arterial vessels of the biliary tree, especially under perfusion with the high viscous University of Wisconsin solution, might be responsible for ischemic type biliary lesions. Due to low viscosity, HTK solution is reported to have a lower incidence of biliary complications. However, there is no data concerning ischemic type biliary lesions in HTK preserved livers. In this paper we report our results after orthotopic liver transplantation with special regard to ischemic type biliary lesions in …
Anti-gout drugs as potential therapy for atrial fibrillation.
2014
Atrial fibrillation (AF) is an important cardiovascular disease in theelderly [1]. Noticeably, it has been increasingly demonstrated thatserum uric acid (UA) is associated with AF [2–9]. In a recent meta-analysis performed by Tamariz and coworkers, the authors concludedthat high levels of UA and AF are clearly associated [10]. Interestingly,serum UA has been linked to AF in obstructive sleep apnea patients[11], whereas it has been also associated with thromboembolic risk inpatients with nonvalvular AF [12].The treatment of gout, a metabolic disorder caused by chronic hyper-uricemia, is based on administration of colchicine, xanthine oxidase (XO)competitive inhibitors such as allopurinol, and…