Xanthine oxidase inhibition by 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors.
Xanthine oxidase (XO), an enzyme involved in purine metabolism, is a source of either oxidants (superoxide radical) or antioxidants (uric acid). Interference with XO activity can lead to oxidative stress, thus contributing to the pathogenesis of cardiovascular diseases. The adenosine receptors antagonist, 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), induces hypertension and cardiovascular injury in rats. Since DPSPX is a xanthine, we aimed at evaluating DPSPX's influence on XO activity to ascertain its contribution to DPSPX-induced hypertension. The activity of isolated XO in the presence of DPSPX was evaluated spectrophotometrically. Serum and urinary uric acid levels of DPSPX-treated rats were measured using a commercial kit. DPSPX inhibited XO activity in a concentration-dependent manner and reduced rat serum and urinary uric acid levels. It can be concluded that: DPSPX is an inhibitor of XO; decreased generation of uric acid may lead to oxidative stress, thus contributing to endothelial dysfunction and vascular morphological changes in DPSPX-treated rats.
Sousa
Teresa
T
Institute of Pharmacology and Therapeutics, Faculty of Medicine of Porto, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Morato
Manuela
M
Fernandes
Eduarda
E
Carvalho
Félix
F
Albino-Teixeira
António
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
D016166:Free Radical Scavengers; D016877:Oxidants; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D014970:Xanthines; D013481:Superoxides; D014527:Uric Acid; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D014969:Xanthine Oxidase; C030985:purine