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The uremic solute indoxyl sulfate acts as an antioxidant against superoxide anion radicals under normal-physiological conditions
Authors:Yohei Miyamoto  Yasunori Iwao  Yuka Tasaki  Yu Ishima  Daisuke Kadowaki  Toru Maruyama  Masaki Otagiri
Affiliation:a Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
b School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada Suruga-ku, Shizuoka 422-8526, Japan
c School of Pharmacy, Kyushu University of Health and Welfare, 1714-1 Yoshino Nobeoka, Miyazaki 882-8508, Japan
d Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
e Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0822, Japan
Abstract:The effect of the uremic solute indoxyl sulfate (IS) on scavenging superoxide anion radicals (View the MathML source) generated from both the xanthine/xanthine oxidase (X/XO) system and activated neutrophils was investigated by electron paramagnetic resonance spectroscopy, combined with 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-1-oxide (EMPO). The findings show that the presence of normal-physiological serum concentrations of IS (0.1-10 μM) resulted in decreased formation of EMPO-superoxide adduct without affecting XO activity. Furthermore, IS showed scavenging activity against cell-derived View the MathML source generated from activated neutrophils. In addition, IS also eliminated hydroxyl radicals. These findings suggest that IS acts as a novel endogenous antioxidant under normal-physiological conditions.
Keywords:IS, indoxyl sulfate   X, xanthine   XO, xanthine oxidase     mmlsi3"   onclick="  submitCitation('/science?_ob=MathURL&  _method=retrieve&  _eid=1-s2.0-S0014579310003315&  _mathId=si3.gif&  _pii=S0014579310003315&  _issn=00145793&  _acct=C000069490&  _version=1&  _userid=6211566&  md5=fce301a470d2cad559bc295f6a834e50')"   style="  cursor:pointer  "   alt="  Click to view the MathML source"   title="  Click to view the MathML source"  >  16"   border="  0"   style="  vertical-align:bottom"   width="  25"   alt="  View the MathML source"   title="  View the MathML source"   src="  http://ars.sciencedirect.com/content/image/1-s2.0-S0014579310003315-si3.gif"  >, superoxide anion radicals     0"   alt="  radical dot"   src="  http://cdn.els-cdn.com/sd/entities/rad"   class="  glyphImg"  >OH, hydroxyl radicals   CKD, chronic kidney diseases   EPR, electron paramagnetic resonance   EMPO, 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-1-oxide   EMPO-OOH, EMPO-superoxide adduct   DMPO, 5,5-dimethyl-1-pyrroline N-oxide   DMPO-OH, DMPO-hydroxyl radical adduct   DTPA, diethylene-triamine-pentaacetic acid   ROS, reactive oxygen species   Cu, Zn-SOD, Cu, Zn-superoxide dismutase   ALP, allopurinol   pterin, 2-amino-4-hydroxypteridine   isoxanthopterin, 2-amino-4,7-dihydroxypteridine   IA, indolacetate   HA, hippurate   CMPF, 3-carboxy-4-methyl-5-propyl-2-furanpropionate
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