No abstract available.
Allopurinol* ; Febuxostat* ; Xanthine Oxidase* ; Xanthine*

Background: One of the causes of inflammatory arthritis is excessive production of uric acid or hyperuricemia. It is a painful disease that is treated with a commercial xanthine oxidase inhibitor to decrease uric acid synthesis. However, the treatment is associated with adverse side effects and thus, there is interest in medicinal plants that could have similar therapeutic effects with minimal side effects. There are many reported indigenous plants and trees in the Philippines that are reported to have therapeutic and bioactive compounds. One such plant is Canarium ovatum or locally called pili. This study aimed to determine the antihyperuricemic activity of the ethanolic extract of the leaves of C. ovatum. Objective: Determine the antihyperuricemic activity of the crude ethanolic extract of C. ovatum leaves and its partially purified fractions through inhibition of xanthine oxidase and its effect on the blood uric acid level of oxonate-induced hyperuricemic mice. Methodology: The crude ethanol extract from C. ovatum leaves and its partially purified fractions obtained through column chromatography were tested for their in vitro xanthine oxidase (XO) inhibitory activity by measuring spectrophotometrically the uric acid formation from xanthine as the substrate. The crude ethanol extract and the fraction with the most XO inhibitory activity were then tested for their in vivo XO inhibitory activity in oxonate-induced hyperuricemic mice by measuring their blood uric acid levels using uric acid test strips. Results: The crude ethanolic extract of C. ovatum leaves at 100ppm showed 83.62±2.05% in vitro inhibition of XO while the most active fraction showed 80.30±4.00% inhibition. Both were comparable (p>0.05) to the positive control, allopurinol, which showed 91.47±5.64% inhibition. In vivo, the crude extract and the fraction that showed the highest XO inhibitory activity at 200 mg/kg significantly (p<0.01 and p<0.05) respectively reduced the serum uric acid levels of the hyperuricemic mice one hour after induction as compared to the negative control. Moreover, their antihyperuricemic activity were not statistically significant as compared to that of allopurinol (p<0.0001). Conclusion The crude ethanolic extract of C. ovatum leaves and its most active fraction showed statistically significant in vitro xanthine oxidase inhibition and in vivo antihyperuricemic activity. The activities shown by both crude and active fraction were not statistically different from that determined for allopurinol. Therefore, further studies can be conducted to isolate the most active compound and study its pharmacokinetic properties.
Xanthine Oxidase ; Uric Acid ; Allopurinol

The author evaluated the optimal concentration of 3 compositions of TIC medium which has used as the melanacytes culture medium. The concentrations of placental extract and bovine pituitary extract, which have the ability to promote proliferation of melanocytes, were evaluated also. Modified TIC medium with above 5 components of evaluated concentration was very effective in melanocytes culture. The results were as follows : l. 12-0-tetradecanoyl-phorbol-13-acetate (TPA) showed effective melanocytes proliferating activity at the concentration of 30ngml (p(0.05) 2. Isobutylmet:hyl xanthine (IBMX) showed effective melanocytes proliferating activity at the concentration of 0.3mM (p(0.05) 3. Cholera toxin (CT) showed effective melanocytes proliferating activity at the concentration of )OnM (p(0.05) 4. Two percentages of placental extract in culture medium showed effective melanocytes proliferating activity. S. Two percentages of bovine pituitary extract in culture medium showed effective melanocytes proliferating activity. 6. Placental extract and isobutylmethyl xanthine proved to have high melanocytes proliferating activity. 7. Melanocytes proliferated rapidly on modified TIC medium (Proliferation doubling time . about 43 hours) 8. The peak time of melanocytes proliferation (7.2 X 10/cm) was observed on the seventh day of culture, From this data, this culture system can be recommended as a new melanocytes culture.
Cholera Toxin ; Humans* ; Melanocytes* ; Tics ; Xanthine

BACKGROUND: The pringle maneuver (PM), hepatic inflow occlusion, during hepatic surgery reduces intraoperative bleeding and blood transfusion requirement, but hepatic ischemia/reperfusion injury is inevitable. During ischemia, xanthine oxidoreductase is converted to xanthine oxidase (XO), which can serve as a critical source of reactive oxygen species (reduces O2 to O2 .-) that contribute to inflammatory signaling, ischemia-reperfusion injury, and an impaired vascular function. The purpose of the present study was to follow changes of XO activity and O2 .- production during hepatic surgery under PM. METHODS: Eleven patients that underwent hepatectomy under intermittent PM were studied. Blood was withdrawn before PM, and 10 and 20 minutes after final reperfusion. Plasma XO activity was measured using a spectrophotometer after incubating plasma with/without xanthine for one-hour. Superoxide (O2 -) production was followed by measuring by cytochrome c reduction by plasma XO. RESULTS: After final reperfusion, plasma XO activity had increased four-fold (0.36 +/- 0.06 to 1.25 +/- 0.25 mU/ml) with a concomitant increase in O2 .- production (0.66 +/- 0.29 to 1.66 +/- 0.40microM/min). CONCLUSIONS: Significantly more XO is released into the systemic circulation after intermittent PM, with subsequently increased O2 .- production. The significant contribution of XO to hepatic surgery under PM might be beneficially managed using an anesthetic with a known antioxidative effect.
Blood Transfusion ; Cytochromes c ; Hemorrhage ; Hepatectomy ; Humans ; Ischemia ; Plasma* ; Reactive Oxygen Species ; Reperfusion ; Reperfusion Injury ; Superoxides ; Xanthine Dehydrogenase ; Xanthine Oxidase* ; Xanthine*

We evaluate the effects of a calcium antagonist(nifedipine) and a xanthine oxidase inhibitor (allopurinol), drugs having a protective effect against shock wave induced renal dysfunction, on acute changes of renal function after piezoelectric ESWL. A total of 40 patients with renal stones undergoing piezoelectric ESWL with LT02 lithotriptor was randomly assigned to 4 groups. Group 1 received no medication and the others received nifedipine(group 2), allopurinol(group 3), and nifedipine plus allopurinol(group 4), respectively. NAG, LDH, 7-GTP, D2M, and microalbumin were measured in the 24-hour urine before and after ESWL. Baseline levels of these parameters were not statistically different between the control group and the others. After ESWL, NAG and microalbumin were significantly increased in group l(p<0.01). In groups 2 and 4, all of the parameters after ESWL were not significantly different from the Values before ESWL. Although the level of NAG after ESWL was significantly higher(p<0.01) than that of the pre-ESWL in group 3, the change of NAG was milder in group 3 comparing to group 1. The range of increase of NAG in groups 2 and 4 were significantly low(<0.01) compared to group 1, and the range of increase of microalbumin in groups 2, 3, 4 were significantly low compared to group l(group 2, 4; p<0.01, group 3; p<0.05). Our results indicate that nifedipine and/or allopurinol can prevent or decrease acute changes of renal function after ESWL using LT02 piezoelectric lithotriptor and especially nifedipine seems to be more efficient than allopurinol.
Allopurinol* ; Calcium ; Humans ; Lithotripsy* ; Nifedipine* ; Shock* ; Urinary Calculi ; Xanthine Oxidase

We evaluate the effects of a calcium antagonist(nifedipine) and a xanthine oxidase inhibitor (allopurinol), drugs having a protective effect against shock wave induced renal dysfunction, on acute changes of renal function after piezoelectric ESWL. A total of 40 patients with renal stones undergoing piezoelectric ESWL with LT02 lithotriptor was randomly assigned to 4 groups. Group 1 received no medication and the others received nifedipine(group 2), allopurinol(group 3), and nifedipine plus allopurinol(group 4), respectively. NAG, LDH, 7-GTP, D2M, and microalbumin were measured in the 24-hour urine before and after ESWL. Baseline levels of these parameters were not statistically different between the control group and the others. After ESWL, NAG and microalbumin were significantly increased in group l(p<0.01). In groups 2 and 4, all of the parameters after ESWL were not significantly different from the Values before ESWL. Although the level of NAG after ESWL was significantly higher(p<0.01) than that of the pre-ESWL in group 3, the change of NAG was milder in group 3 comparing to group 1. The range of increase of NAG in groups 2 and 4 were significantly low(<0.01) compared to group 1, and the range of increase of microalbumin in groups 2, 3, 4 were significantly low compared to group l(group 2, 4; p<0.01, group 3; p<0.05). Our results indicate that nifedipine and/or allopurinol can prevent or decrease acute changes of renal function after ESWL using LT02 piezoelectric lithotriptor and especially nifedipine seems to be more efficient than allopurinol.
Allopurinol* ; Calcium ; Humans ; Lithotripsy* ; Nifedipine* ; Shock* ; Urinary Calculi ; Xanthine Oxidase

OBJECTIVETo evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase (XO) activity in vitro and to analyze the mechanism of this effect.

METHODSIn this in vitro study, Kinetic measurements were performed in 4 different inhibitor concentrations and 5 different xanthine concentrations (60, 100, 200, 300, 400 Μmol/L). Dixon and Lineweaver-Burk plot analysis were used to determine Ki values and the inhibition mode for the compounds isolated from Gnaphalium affine extract.

RESULTSFour potent xanthine oxidase inhibitors were found in 95% ethanolic (v/v) Gnaphalium affine extract. Among them, the flavone Eupatilin exhibited the strongest inhibitory effect on XO with a inhibition constant (Ki) of 0.37 Μmol/L, lower than the Ki of allopurinol (4.56 mol/L), a known synthetic XO inhibitor. Apigenin (Ki of 0.56 Μmol/L, a proportion of 0.0053‰ in Gnaphalium affine), luteolin (Ki of 2.63 Μmol/L, 0.0032‰ in Gnaphalium affine) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (Ki of 3.15 Μmol/L, 0.0043‰ in Gnaphalium affine) also contributed to the inhibitory effect of Gnaphalium affine extract on XO activity.

CONCLUSIONSThese results suggest that the use of Gnaphalium affine in the treatment of gout could be attributed to its inhibitory effect on XO. This study provides a rational basis for the traditional use of Gnaphalium affine against gout.

To observe the activity of the xanthine oxidase in cerebral ischemia, an ischemic model was made using a transorbital occlusion of the middle cerebral artery(MCA) in cats. Xanthine oxidase activity was measured by means of high performance liquid chromatography with electrochemical detection of uric acid. The results were as follows: The infarction in the territory of the left middle cerebral artery(MCA) was identified with intracardiac perfusion of a 2% triphenyltetrazolium chloride(TTC) solution after transorbital occusion. 2) There was no significant difference between the control and ischemia groups in the total xanthine oxidase activity. 3) In the control group, 38.2% of the total xanthine oxidase was in the oxygen-dependent superoxide-producing oxidase group(Type 0). It had been increased with time in ischemia, despite the total xanthine oxidase activity remaining the same;particularly at 12 hours(p<0.05) and 24 hours(p<0.01) after occlusion of the left MCA. 4) In the healthy side, the activity of type 0 and its ratio to the total xanthine oxidase activity has not been increased. 5) In the ischemic side, the conversion of type D xanthine oxidase to the type 0 xanthine oxidase was demonstrated and its rate had been increased with the passage of time.
Animals ; Brain Ischemia ; Cats ; Cerebral Infarction* ; Chromatography, Liquid ; Free Radicals ; Infarction ; Ischemia ; Oxidoreductases ; Perfusion ; Uric Acid ; Xanthine Oxidase* ; Xanthine*

PURPOSE: It has been suggested in our previous study that the level of xanthine oxidase(XO) activity, glutathione(GSH) and malonydialdehyde(MDA) in renal tissue following renal ischemia/reperfusion(I/R) could be used as marker of oxidant stress. Present study was undertaken to investigate the serum level of XO activity. GSH and MDA following renal I/R and to elucidate potential use of the serum level of GS H and MDA as makers of renal function following I/R injury. MATERIALS AND METHODS: Male Sprague-Dawley rats(200-250gm) were divided into 3 groups : group A - occlusion of bilateral renal arteries for 60 min, group B - pretreatment allopurinol(20mg/Kg). a radical scavenger, plus occlusion of renal arteries, and group C(control group) - sham operation. In group A and B, recirculation of renal arteries were performed for 30min. XO activity, xanthine dehydrogenase(XD) type conversion ratio, level of GSH and MDA were measured from venous blood. RESULTS: Both XO activity(nM/mg/min) and XD type conversion ratio(%) were increased in group A(XO; 0.173+/-0.012, XD; 60.44+/-4.32) and decreased in group B(XO; 0.136+/-0.01, XD; 45.40+/-4.78) compared to control group(XO; 0.153+/-0.012, XD; 46.93+/- 3.45). The level of GSH(microM/g tissue), a scavenger of oxygen free radical(OFR), was also decreased in group A(0.130+/-0.021) compared to group B(0.179+/-0.021) and control group(0.186+/-0.017). In addition, the level of MDA(nM/g tissue), which is a stable end product of lipid peroxidation, was significantly increased in group A(0.076+/-0.006) compared to group B(0.057+/-0.005) and control group(0.053+/-0.004). CONCLUSIONS: From these results, it is suggested that renal I/R injury is highly correlated with the production of OFR. Furthermore. the serum levels of MDA and GSH might be used as early markers of oxidant stress in association with renal I/R injury.
Animals ; Glutathione* ; Humans ; Lipid Peroxidation ; Male ; Malondialdehyde* ; Oxygen ; Rats* ; Rats, Sprague-Dawley ; Renal Artery ; Xanthine Oxidase* ; Xanthine*

To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.
Antioxidants ; Chickens ; Glutathione Peroxidase ; Hyperuricemia ; Infectious bronchitis virus* ; Kidney ; Malondialdehyde ; RNA, Messenger* ; Superoxide Dismutase ; Uric Acid ; Xanthine Oxidase* ; Xanthine*