Hepatic Xanthine Dehydrogenase Research Articles

Inhibitory Effects of Apium graveolens on Xanthine Oxidase Activity and Serum Uric Acid Levels in Hyperuricemic Mice.

Celery (Apium graveolens) is traditionally used to treat rheumatism and cardiovascular disorders. Hyperuricemia is considered as a predisposing factor for gout and is also suggested to be associated with coronary artery disease. In the present study, the effect of hydroalcoholic extracts from A. graveolens (AGE) against potassium oxonate (PO)-induced hyperuricemia was investigated in mice. AGE (250, 500, and 1,000 mg/kg) or allopurinol (5 mg/kg, as positive control) were orally administrated 1 h after PO injection (250 mg/kg, ip) for two weeks. After that, the serum uric acid level and hepatic xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities were measured. In addition, the antioxidant activity of AGE was determined by assessment of hepatic lipid peroxidation, in vivo and the ferric reducing/antioxidant power assay, in vitro. The extract exhibited good capacity to reduce ferric ion to ferrous ion with mean value of 63.8±8.5 μmol/g. The data also showed that oxonate treatment produced a significant increase in serum uric acid level (4.6 vs. 2.3 mg/ dL, P<0.001), liver XO/XDH activities (P<0.01 and P<0.001, respectively), and hepatic lipid peroxides levels (about two fold, P<0.01), compared to the healthy mice. AGE significantly decreased the serum uric acid level, hepatic XO/XDH activities, and lipid peroxidation, in a dose-dependent manner. Oral administration of 1,000 mg/kg AGE for two weeks reversed the elevated serum uric acid level (2.7 vs. 4.6 mg/dL, P<0.001) and significantly inhibited liver XO/XDH activities (P<0.001) and diminished hepatic lipid peroxidation (0.45 vs. 0.82 nmol/mg protein, P<0.05), compared with hyperuricemic mice. AGE (1,000 mg/kg) per se did not significantly modify these parameters. Our results demonstrated that AGE could reduce the serum uric acid level via inhibition of hepatic XDH/XO and indicated its potential utility as an effective hypouricemic bioactive agent or functional food.

Regulation of Xanthine Dehydrogenase in Rat Liver in Response to Peroxisome Proliferators

Previously we found a depression in the activity of hepatic xanthine dehydrogenase in rats fed clofibrate or di(2-ethylhexyl)phthalate. The present study further demonstrated that dietary addition of other peroxisome proliferators, including bezafibrate, dehydroepiandrosterone and perfluoro-n-octanoic acid also depressed activity of hepatic xanthine dehydrogenase in rats. Western and Northern blot analyses indicated the depression in hepatic xanthine dehydrogenase protein and mRNA by feeding bezafibrate. These results suggest that administration of a wide variety of peroxisome proliferators depresses the activity of hepatic xanthine dehydrogenase in rats and that the depression in activity of this enzyme by the proliferator might be mediated by decreased mRNA of the enzyme. Further, nuclear run-on analysis revealed no influence of feeding bezafibrate on the transcriptional activity of hepatic xanthine dehydrogenase gene, suggesting increased degradation of the enzyme mRNA by the chemical.

Endotoxin induces bacterial translocation and increases xanthine oxidase activity.

Previously, we documented that endotoxin induces bacterial translocation from the gut and that inhibition or inactivation of xanthine oxidase activity reduces endotoxin-induced bacterial translocation. Consequently, experiments were performed to correlate endotoxin-induced bacterial translocation with changes in intestinal mucosal structure and xanthine dehydrogenase and oxidase activity. Segments of the jejunum, ileum, cecum, proximal colon, distal colon, and liver were harvested from ICR mice 24 hr after IP administration of E. coli 0111:B4 endotoxin (0.1 mg). Xanthine dehydrogenase and oxidase activities were measured in these samples and correlated with intestinal morphology. Bacteria translocated from the intestines to extraintestinal organs in 70% of the mice receiving endotoxin, while the organs of control mice were sterile (p less than 0.01). Endotoxin injured primarily the ileal and cecal mucosa and increased ileal and hepatic xanthine dehydrogenase and cecal oxidase activities (p less than 0.05). These results suggest that xanthine oxidase-induced mucosal damage plays a role in endotoxin-induced bacterial translocation.

The effect of hyperthermia on conversion of rat hepatic xanthine dehydrogenase to xanthine oxidase

The effect of hyperthermia on conversion of rat hepatic xanthine dehydrogenase to xanthine oxidase

Hepatic xanthine dehydrogenase and plasma uric acid in broiler chickens fed various amounts of dietary methionine, protein and energy

SummaryIn four consecutive experiments, plasma uric acid (PUA), hepatic xanthine dehydrogenase (XDH) and body-weight gains (WG) of broiler chickens were measured under varying dietary methionine, protein and energy. In Expt 1, increases in WG with increasing dietary methionine peaked at 0·60%, a level where the initial decreases in either PUA or XDH reached a minimum. PUA and XDH in broiler finishers (Expt 2) decreased between 0·26 and 0·50% dietary methionine while WG improved between 0·26 and 0·50% methionine. XDH in the 18% protein and 0·68% methionine + cystine (MC) diet combination for Expt 3 was 66·4 μtmol/10 min/total liver weight, a value higher than either the 43·5 or 46·5 μtmol/10 min/total liver weight, respectively obtained in the 21% protein + 0·68% MC and 24% protein + 0·68% MC diet combinations. Both PUA and XDH, however, increased with increasing dietary protein when MC was either 0·76 or 0·84% diet. XDH in Expt 4 decreased between 11·7 and 13·4 MJ ME/kg diet that contained either 0·76 or 0·84% MC, tending not to vary between 13·4 and 15·1 MJ ME/kg diet. This enzyme activity remained essentially similar between 11·7 and 15·1 MJ ME/kg diet that contained 0·68% MC.

Enzymatic correlates and ontogeny of uricotelism in tree frogs of the genus Phyllomedusa

AbstractActivities of arginase, xanthine dehydrogenase, and uricase were measured in liver and kidney of adult Phyllomedusa sauvagei and P. hypochondrialis to examine the enzymatic basis of their unusual ability to excrete uric acid. Comparable values were obtained for two species of ureotelic anurans and a uricotelic lizard. Both Phyllomedusa species exhibited high hepatic and renal levels of xanthine dehydrogenase, whereas this enzyme was not detected in the livers of the ureotelic frogs or the lizard. Hepatic xanthine dehydrogenase was significantly higher in P. sauvagei, which excretes urate predominantly, than in P. hypochondrialis, which excretes 20% of its nitrogen as urate. Hepatic arginase was much lower in both Phyllomedusa species than in the ureotelic frogs, but higher than in the lizard. Reduced levels of uricase were also associated with uricotelism in this genus.Xanthine dehydrogenase was present in livers of larval P. sauvagei well in advance of the onset of uric acid excretion late in metamorphosis. Premetamorphic larvae excreted over 50% of their nitrogen waste as urea and the balance as ammonia.

The influence of tungsten on the molybdenum status of poultry.

1. Large doses of tungsten, administered to the chick either by injection or by feeding, increased tissue concentrations of tungsten and decreased tissue concentrations of molybdenum and tissue activities of xanthine dehydrogenase. 2. The rate of loss of large doses of tungsten from the liver occurred in an exponential manner with a half-life of 27 h. 3. When tungsten was administered to chicks fed on a semi-synthetic diet containing abnormally low concentrations of molybdenum, the activity of hepatic xanthine dehydrogenase was reduced to negligible levels. 4. The alterations in molybdenum metabolism resulting from the administration of large doses of tungsten to the chick appears to be the result of tungsten toxicity and not of molybdenum deficiency. 5. Deaths from tungsten toxicity occurred when tissue concentrations of tungsten were increased to approximately 25 micrograms/g liver. At this tissue tungstencon centration the activity of xanthine dehydrogenase was zero.

Some effects of vitamin E deficiency on hepatic xanthine dehydrogenase activity, lead, and α-tocopherol concentrations in tissues of lead-dosed mallard ducks

Three experiments were conducted to determine whether vitamin E deficiency (−E) and/or the oral administration of lead (300 mg/kg body weight) to mallard ducks would affect hepatic xanthine dehydrogenase (XDH) activity and tissue lead deposition. Although there was a significant difference between the +E and −E plasma α-tocopherol (PαT) and liver α-tocopherol (LαT) concentrations in Experiment 1, XDH activity was unaffected. In Experiment 2, 1-day-old ducklings were fed the experimental diets for 14 days and then given lead (Pb). Forty-eight hours after dosing with Pb the results obtained were similar to those in Experiment 1 except that LαT was distinctly elevated and XDH activity per gram wet weight of liver was significantly depressed in the Pb-treated groups. With Pb treatment the whole blood and liver Pb content was markedly increased. After 96 hr, whole blood, liver, kidney, and spleen Pb concentrations in the +E+Pb group were significantly greater than that in the −E+Pb group. In Experiment 3, 30-week-old, vitamin E-depleted drakes fed diets similar to those above showed normal XDH activity but marked differences in PαT and LαT were observed. Again the liver Pb content of the +E+Pb group was signficantly greater than of the −E+Pb group. It appears that XDH activity is not responsive to vitamin E deficiency. Also tissue Pb content, with the exception of drake whole blood lead concentrations, seems to be positively related to vitamin E status.

An immunochemical study of the changes in chicken liver xanthine dehydrogenase activity during dietary adaptation.

A specific rabbit antiserum was prepared against chicken liver xanthine dehydrogenase [EC 1.2.1.37] and used to investigate changes in the amount of the enzyme protein in the liver during dietary adaptation. When the enzyme activity was decreased by the administration of a low protein diet, quantitative immunoprecipitation and Laurell electroimmunoassay showed not only a decrease in the amount of the enzyme antigen but also a reduction of the apparent molecular activity of the enzyme. This was confirmed by the finding that the activity-flavin ratio and the activity-molybdenum ratio of the enzyme were lowered in chickens adapted to the low protein diet. The relative rate of synthesis of xanthine dehydrogenase, expressed as radioactivity incorporated into the enzyme protein divided by radioactivity incorporated into total cell homog-enate protein, was measured by pulse-labeling the liver protein with L-[4,5−33H]leucine. Xanthine dehydrogenase was isolated by quantitative immunoprecipitation followed by electrophoresis of the dissolved immunoprecipitate on sodium dodecyl sulfate-polyacrylamide gel. The relative rate of synthesis increased 6– to 9–fold, while the enzyme activity increased 10– to 30–fold in vivo following the administration of a high protein diet. The rate of degradation of xanthine dehydrogenase was higher in chickens adapted to the low protein diet than in those adapted to the high protein diet, the apparent half lives being 1 day and 3 days, respectively. Although some limitations and assumptions were present in the techniques used in these experiments, these results suggest that the increase in the hepatic xanthine dehydrogenase content in the chickens adapted to the high protein diet was mainly due to a rise in the rate of enzyme synthesis and, to a minor degree, to a decrease in the rate of enzyme degradation.

Purification of hepatic xanthine dehydrogenase from chicken fed a high-protein diet

Xanthine dehydrogenase (xanthine:NAD + oxidoreductase, EC 1.2.1.37 of high specific activity was obtained from chicken liver. As a starting material the livers of chicken fed a high-protein diet were adopted. In the absorption spectrum of the purified enzyme the ratio A 280 nm /A 450 nm was 5.54, which suggests a high purity. The specific activity of the purified enzyme was 1200 and 57 as expressed by the turnover number and the activity protein ratio respectively.

Changes in Liver Xanthine Dehydrogenase and Uric Acid Excretion in Chicks during Adaptation to a High Protein Diet

Studies were conducted to examine the relationship between changes in liver xanthine dehydrogenase with those in uric acid excretion during a 10-day adaptation period in chicks fed diets containing 25 or 75% isolated soybean protein. Food consumption, weight gain and liver nitrogen were also determined. Marked reductions in food consumption and weight gain were noted the first 24 hours in chicks fed the high protein diet as compared with chicks fed a control diet containing 25% isolated soybean protein. Consumption of the high protein diet and weight gain increased markedly after the initial 24 hours and remained at approximately 80% of the levels observed for control chicks throughout the remainder of the experiment. Liver weight, expressed on a body weight basis, was significantly increased in chicks fed the high protein diet for the first 2 days, after which time the differences between the 2 treatment groups largely disappeared. Elevated liver nitrogen levels were observed throughout the experiment for birds fed the high protein diet. Liver xanthine dehydrogenase activity increased twofold in chicks fed the high protein diet for 1 day and reached a maximum fourfold increase by day 4. A direct relationship between the elevated activity of hepatic xanthine dehydrogenase measured in vitro and the uric acid excretion was observed in these studies.