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.

Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle

Abstract: Experiments were designed to determine the role of oxygen-derived free radicals in modulating contractions of vascular smooth muscle and endothelium-mediated relaxations to acetylcholine. The effects of generating or scavenging these radicals were studied in rings of canine coronary arteries suspended for isometric tension recording. Xanthine oxidase plus xanthine caused relaxations, which were greater in rings with endothelium than in rings without endothelium; the relaxations were not affected by superoxide dismutase or mannitol, but could be prevented by catalase. Xanthine oxidase plus xanthine depressed endothelium-mediated relaxations to acetylcholine; this effect was prevented by superoxide dismutase, but was not affected by catalase or mannitol. Exogenous hydrogen peroxide induced catalase-sensitive relaxations, which were depressed by the removal of the endothelium. Superoxide dismutase evoked catalase-sensitive relaxations only in rings with endothelium. Endothelium-mediated relaxations to acetylcholine were slightly depressed by superoxide dismutase or catalase alone; the combination of the two enzymes or mannitol caused a major shift to the right of the concentration-response curve to acetylcholine. In rings without endothelium, relaxations caused by sodium nitroprusside were not affected by the scavengers (alone or in combination) but were augmented by xanthine oxidase plus xanthine. These data suggest that the endothelium-derived relaxing factor released by acetylcholine is not likely to be an oxygen-derived free radical; hydrogen peroxide has a direct inhibitory action on coronary arterial smooth muscle and triggers endothelium-dependent relaxations; and superoxide anions depress and hydroxyl radicals facilitate endothelium-dependent relaxations caused by activation of muscarinic receptors.

The inhibition of nucleic acid synthesis by mycophenolic acid

Abstract: 1 Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro 2 The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [(14)C]thymidine 3 The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine 4 The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine 5 Mycophenolic acid does not inhibit the incorporation of [(14)C]thymidine into DNA in suspensions of Landschutz and Yoshida ascites cells in vitro 6 Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschutz and Yoshida ascites cells and also in L cells in vitro There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic 7 Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschutz cells capable of converting hypoxanthine into IMP, XMP and GMP 8 Preparations of IMP dehydrogenase from Landschutz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid The inhibition showed mixed type kinetics with K(i) values of between 303x10(-8) and 45x10(-8)m 9 Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschutz and Yoshida ascites cells and L cells in vitro

Use of a xanthine oxidase free radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa

Abstract: The reaction between xanthine and xanthine oxidase results in the univalent and divalent reduction of dioxygen to generate superoxide (O2-.) and hydrogen peroxide (H2O2), respectively. With the aid of this system, the direct effect of reactive oxygen species (ROS) on human sperm function has been investigated. A protocol involving the addition of xanthine oxidase to the reaction mixture at 0 and 15 min resulted in a loss of motility involving every component of sperm movement examined. Lower doses of xanthine oxidase, which did not influence sperm motility, were also found to suppress the competence of human spermatozoa to exhibit oocyte fusion in response to the ionophore, A23187. The reactive oxygen species responsible for the disruption of human sperm function was not influenced by the presence of superoxide dismutase (SOD) or scavengers of hypochlorous acid or hydroxyl radicals. However, the cytotoxic species was shown to be extremely stable and could be completely eliminated by catalase, which selectively eliminates H2O2. Confirmation that it is H2O2, and not O2-., which is cytotoxic to human spermatozoa was obtained in studies in which the direct addition of this oxidant was shown to influence both the movement of human spermatozoa and their competence for oocyte fusion. These results carry implications for the diagnosis of defective sperm function and the design of optimized culture media for the treatment of male factor infertility.

Excretion of purine derivatives by ruminants : effect of microbial nucleic acid infusion on purine derivative excretion by steers

Abstract: Two steers totally nourished by intragastric infusion of volatile fatty acids and casein were given an abomasal infusion of a microbial protein preparation (Pruteen) at eight rates with a purine input ranging from 0 to 170 mmol/day over 11 successive 5-day periods. The urinary excretion of purine derivatives relative to the purine input was measured. Negligible amounts of xanthine plus hypoxanthine were present in the urine. The relative contributions of allantoin and uric acid to the total excretion were not affected by the rate of purine infusion. Total purine derivative excretion (uric acid and allantoin) was linearly correlated with purine input. Recovery in the urine of the infused purines was 0·77. It is suggested that utilization of exogenous purines may only occur in the intestinal mucosa and that the remaining purines may be completely converted, before entering the liver, to uric acid and allantoin, which are subsequently eliminated by the renal and extrarenal routes. The differences between cattle and sheep in excretion of purine derivatives, and the implications of these differences for the use of purine excretion values in order to estimate microbial protein supply to the ruminant, are discussed.