Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.

Effects of reactive oxygen and nitrogen species on cyclooxygenase-1 and -2 activities.

Abstract: The effects of reactive oxygen species (superoxide anion radical—O 2 − , hydrogen peroxide—H 2 O 2 and hydroxyl radical— OH; the reaction products of xanthine plus xanthine oxidase system) and reactive nitrogen species [nitric oxide—NO ; from 1-hydroxyl-2-oxo-3-( N -methyl-3-aminopropyl)-3-methyl-1-triazene—NOC7 and peroxynitrite—ONOO − ] on the activities of purified cyclooxygenase (COX)-1 and -2 were studied. Xanthine plus xanthine oxidase suppressed the COX-1 and -2 activities in a xanthine oxidase concentration-dependent fashion. This effect was reversed by addition of catalase to the reactive oxygen species-generating system but not by superoxide dismutase or mannitol, indicating that H 2 O 2 is the responsible metabolite. NOC7 activated the COX-1 activity but inhibited the COX-2 activity at concentrations ranging from 1 to 50μM. Experiments utilizing a NO antidote, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide revealed that the observed effects of NOC7 are caused by NO . ONOO − , a product of NO and O 2 − , both activated and inhibited the COX-1 and -2 activities, depending on ONOO − concentration. At a low concentration of ONOO − (5μM) there was enhancement of the COX-1 and -2 activities, but with higher concentrations there was suppression of these two enzyme activities (COX-1, at 200μM; COX-2, >50μM). These results suggest that H 2 O 2 , NO and ONOO − can have different modulatory effects on the COX-1 and -2 activities.

Inhibition of nitric oxide synthase by a superoxide generating system

Abstract: Although superoxide anion is known to inactivate nitric oxide (NO) once formed, its effect on NO synthesis is unclear. In this study, xanthine oxidase-hypoxanthine, a superoxide anion generating system, inhibited bovine cerebellum NO synthase activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. This inhibition by xanthine oxidase was concentration-dependent. Superoxide dismutase-catalase and allopurinol, an inhibitor of xanthine oxidase, attenuated in part the inhibition of NO synthase activity by xanthine oxidase. Xanthine oxidase also produced a decrease in the partial pressure of oxygen in the assay mixture. The inhibition of NO synthase activity by xanthine oxidase was reversed completely when oxygen was passed continuously through the reaction mixture. This study suggests that a decrease in oxygen concentration caused by superoxide generation may inhibit NO synthesis.

Role of purines and xanthine oxidase in reperfusion injury in perfused rat liver.

Abstract: The purpose of this study was to evaluate the possible involvement of xanthine and xanthine oxidase in reperfusion injury in a low-flow, reflow model of liver perfusion. Livers were perfused at flow rates around 25% of normal for 90 min and then at normal flow rates (4 ml/g/min) for 30 min. When flow was restored to normal, malondialdehyde and lactic dehydrogenase (LDH) were released into the effluent perfusate. Malondialdehyde production rapidly reached values of 300 nmol/g/hr whereas LDH increased from basal levels of 100 to 600 U/l upon reperfusion. Trypan blue was taken up exclusively in cells in pericentral regions of the liver lobule under these conditions. Xanthine and hypoxanthine in the effluent perfusate increased steadily during the low-flow period reaching values around 5 and 10 microM, respectively, and decreased rapidly after the flow was restored to normal. Perfusion with nitrogen-saturated buffer for 3 min before restoration of normal flow rates or infusion of the radical scavenger catechin (400 microM) reduced cell damage by about 50%. Infusion of allopurinol (2-6 mM), an inhibitor of xanthine oxidase, prevented reperfusion injury in a dose-dependent manner. Taken together, these data indicate that a reperfusion injury occurs in liver upon reintroduction of oxygen which is initiated by oxidation of xanthine and hypoxanthine via xanthine oxidase and ultimately leads to production of lipid peroxides. Surprisingly, infusion of xanthine (4 mM), substrate for xanthine oxidase, reduced hepatocellular injury on reperfusion. LDH release was decreased from values around 700 to less than 200 U/l and trypan blue uptake in pericentral region was prevented totally by xanthine.(ABSTRACT TRUNCATED AT 250 WORDS)