• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.258-266
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• 2015

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMFA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMFA models were generated using different alignments and the best model yielded a cross-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.88-96
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• 2001

To evaluate the effect of Yuldahansotang(YHT) water extract on cultuted mouse spinal sensory neuron which was inhibited by xanthine oxidase(XO) and hypoxanthine(HX)-induced oxigen radicals, MIT assay, NR assay, Neurofilament enzymeimmuno assay and LDH activity assay were carried our after the cultured mouse spinal sensory neuron were preincubated with various concentrations of YHT water extract for 3 hours prior to exposure of XO/HX. The results obtained were as follows: 1. XO/HX, a oxigen radical, decreased the survival rate of the cultured mouse spinal sensory neuron cells on NR assay and MTT assay. 2. MTT50 value and NR50 value pf XO/HX were 20 mU/ml XO/0.2 mM HX and 40 mU/ml XO/0.2 mM HX. 3. YHT water extract have efficacy of increasing neurofilament. 4. YHT water extract have efficacy of increasing LDH activity. From above the results, It is concluded that YHT has marked efficacy as a treatment for the damages caused in the XO/HX-mediated oxidative process.

• Biomedical Science Letters
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• v.8 no.1
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• pp.47-52
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• 2002

To investigate an effect of cyclohexanone (CHO) treatment on the serum levels of xanthine oxidase (XO) in liver damaged animals, the rats were intraperitoneally pretreated with 50% carbon tetrachloride ($CCl_4$) in olive oil (0.1 mL/ 100 g body weight) 14 times every other day. To the $CCl_4$-pretreated rats, CHO (1.56 g/kg body weight) was injected once and then the animals were sacrificed at 4 hours after CHO treatment. The increasing rate of serum and liver XO activities to the control was higher in CHO-treated animals pretreated with $CCl_4$ than the $CCl_4$-pretreated those. Concomitantly CHO injection to the $CCl_4$-pretreated animals showed somewhat higher Vmax and lower Km value in the kinetics of liver XO enzyme. Furthermore, increasing rate of hepatic malonedialdehyde content to the control was also higher in CHO-treated animals pretreated with $CCl_4$ than $CCl_4$-pretreated those. On the other hand, the injection of CHO to the $CCl_4$-pretreated animals showed the more enhanced liver damage on the basis of liver function finding; liver weight per body weight (%), serum levels of alanine aminotransferase activity and hepatic glucose-6-phosphatase activity. In conclusion, injection of CHO to the $CCl_4$-pretreated rats led to more increased activity of serum XO and it may be caused by acceleration of hepatocyte membrane permeability and induction of enzyme protein.

• Korean Journal of Animal Reproduction
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• v.26 no.3
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• pp.263-273
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• 2002

This study was undertaken to evaluate the effects of $\beta$-mercaptoethanol ($\beta$-ME) on lipid peroxidation and fertilization ability in vitro by xanthine (X) - xanthine oxidase (XO) system in boar spermatozoa frozen-thawed. The boar spermatozoa were treated with X and/or XO, and the spermatozoa viability were measured by the eosin-nigrosin stain method. In control group, level of vitality in boar spermatozoa were higher than in medium with X, XO and X+XO groups. No significant differences, however, were observed under the all conditions. The percentage of spermatozoa that reached acrosome reaction were significantly (P<0.05) higher in sperm treated without that than with $\beta$-ME under the all conditions. On the other hand, when spermatozoa were inseminated in medium with X and/or XO, the penetration rates in all conditions were higher in medium with that than without $\beta$-ME. However, significant differences were not observed between medium with and without $\beta$-ME. The lipid peroxidation of sperm was evaluated on the basis of malondialdehyde (MDA) production. The MDA were higher in sperm treated without that than with $\beta$-ME under the above all conditions. However, significant differences were not observed between medium with and without $\beta$-ME. Sperm-SH group were higher detected in medium with that than without $\beta$-ME under the all conditions. The activity of sperm binding to Bona pellucida was also evaluated through binding to salt-stored porcine oocytes. In control group, sperm binding to zona pellucida were significantly (P<0.05) higher than in medium with X+XO groups. The sperm binding in all conditions were higher in medium with that than without $\beta$-ME. However, significant differences were not observed between medium with and without $\beta$-ME. These results suggest that addition of $\beta$-ME in X-XO system may play a positive role in improving of fertilization ability in vitro.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.553-556
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• 2002

To study the effects of Scorpio on oxygen free radical-mediated damage by xanthine oxidase/hypoxanthine (XO/HX) on cultured spinal sensory neurons, in vitro assays such as MTT assay were used in cultured spinal sensory neurons derived from mice. Spinal sensory neurons were cultured in media containing various concentrations of XO/HX for 6 hours, after which the neurotoxic effect of XO/HX was measured by in vitro assay. The protective effect of the herb extract, Scorpio water extract against XO/HX-induced neurotoxicity was also examined. The results are as follows : In MTT assay, XO/HX significantly decreased the cell viability of cultured mouse spinal sensory neurons according to exposure concentration and time in these cultures. The effect of Scorpio water extract on XO/HX-induced neurotoxicity showed a quantitative increase in neurdfilament. These results suggest that XO/HX has a neurotoxic effect on cultured spinal sensory neurons from mice and that the herb extract, Scorpio water extract, was very effective in protecting XO/HX-induced neurotoxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.549-552
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• 2003

To investigate the protective effect of Sophorae Radix (SR) on the damage by pulmonary vascular endothelial cells by xanthine oxidase (XO)/hypoxanthine (HX)-induced oxygen tree radical, Neutral Red (NR) and c-fos immunopositive cell assay were used. The results were obtained as follows ; The viability of vascular endothelial cells treated with XO/HX was decreased. And c-fos immunopositive cells represented a maximal increase in group treated with XO/HX for 2 hour in pulmonary vasvular endothelial cells. But pretreated groups with SR extracts were not inhibited the increase of c-fos immunopositive cells by XO/HX in a dose-dependent manner. These results show that XO/HX elicits toxic effects in cultured pulmonary vascular endothelial cells, and suggest that SR extract is very effective in the prevention of XO/HX-induced increase of c-fos immunopositive cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.443-446
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• 2003

To investigate the protective effect of Bulbus Allii Macrostemi (BAM) on the damage by pulmonary vascular endothelial cells by xanthine oxidase (XO)/hypoxanthine (HX)-induced oxygen free radical, Neutral Red (NR) and protein kinase c (PKC) activity assay were used. The results were obtained as follows ; The viability of vascular endothelial cells treated with XO/HX was decreased. And activation of PKC represented a maximal increase in group treated with XO/HX for 15 mins in vasvular pulmonary endothelial cells. But pretreated groups with BAM extracts were not inhibited the increase of PKC activation by XO/HX in a dose-dependent fashion. These results show that XO/HX elicits toxic effects in cultured pulmonary vascular endothelial cells, and suggest that BAM extract is very effective in the prevention of XO/HX-induced PKC activation.

• Applied Microscopy
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• v.31 no.1
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• pp.37-47
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• 2001

In order to investigate a pathogenesis of liver damage induced by skin burn, thermal injury was induced by scald burn on entirely dorsal surface in rats (total burn surface area $20\sim25\%$) except for inhalated injury. At 5 and 24 h after scald burn, biochemical assay and morphological changes in serum and liver tissue were examined. Skin burn increased liver weight (% of body weight, p<0.05) and the activity of serum aniline amino-transferase (ALT, p<0.05), in addition, the activity of xanthine oxidase (XO), an enzyme of oxygen free radical generating system, was elevated (p<0.01) in serum, but not in skin and in liver. Postburn treatment of allopurinol intraperitoneally decreased liver weight, serum ALT activity and serum XO activity. Scald burn induced ultrastructurally swelling of endoplasmic reticulum, ribosome detachment, accumulation of lipid, dilatation of bile canaliculi and intercellular space, neutrophil infiltration, activation of Kupffer's cells and degeneration of hepatocytic microvilli. Futhermore , thermal injury decreased not only the protein concentration in plasma but also the number of intravascular leukocytes, that indicates induction of edema formation with protein exudation and inflammation by neutrophil infiltration into the internal organs. However allopurinol injection after burn inhibited post burn ultrastructural changes. These data suggest that acute dermal scald burn injury leads to liver damage, that is related to elevation of xanthine oxidase activity in serum. Xanthine oxidase may be a key role in the pathogenesis of liver damage induced by skin burn.

• Journal of Acupuncture Research
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• v.40 no.2
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• pp.135-142
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• 2023

Background: This study aimed to investigate hyperuricemia, renal inflammation, and xanthine oxidase (XO) activity improvement in a rat model treated with Scutellaria baicalensis extract (SBE). Methods: The rats were divided into 4 groups (n = 5 each), including sham, potassium oxonate (PO) injected hyperuricemia (control group), PO + 10 mg/kg allopurinol administrated (allopurinol group), and a PO + 50 mg/kg SBE administrated (SBE group), to investigate the effectiveness and molecular mechanisms of SBE. The effects of SBE on PO-induced hyperuricemia rats, renal inflammation, and XO activity were measured. Body weight and organ index of the kidney and liver were measured in PO-induced hyperuricemia rats, and serum uric acid level was extracted from whole blood and was measured. Renal inflammation was observed under a microscope after sections. XO activity was measured by liver tissue and serum XO levels. Results: Organ indexes of the kidney and liver in rats were significantly decreased in the allopurinol group than in the control group and with no significant difference in the SBE group. A PO injection for 5 days significantly increased serum uric acid levels in the control group compared to the sham group. Meanwhile, the SBE and allopurinol groups have significantly decreased serum uric acid levels compared to the control group. The SBE group revealed effectively improved renal histopathological changes compared to the control group. The XO inhibitor, allopurinol, significantly decreased XO activity. Additionally, SBE significantly lowered XO activity in rats. Conclusion: SBE can be used as an effective treatment for gout in the future.

• Journal of Acupuncture Research
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• v.40 no.1
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• pp.53-60
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• 2023

Background: This study aimed to investigate the effects of Oenanthe javanica (OJ) extracts on rats with potassium oxonate (PO)-induced hyperuricemia. Methods: The effects of OJ extract on rats with PO-induced hyperuricemia-induced were monitored. Changes in the body weight and organ indices of hyperuricemic rats were calculated to detect anti-hyperuricemic effects. Blood samples were collected to observe the effect of reducing serum uric acid concentration. Kidney tissues were stained to observe histopathological changes under a microscope. The activity of xanthine oxidase (XO), which catalyzes xanthine to uric acid in the liver, was assessed to observe the inhibitory effect of XO. Results: 1. The body weight of hyperuricemic rats showed no considerable differences between the control group and the treatment group. The OJ group had significantly improved liver index, whereas the allopurinol group had improved liver and kidney indices. 2. Serum uric acid levels increased significantly after PO injection, and the OJ and allopurinol groups showed a significant reduction effect. 3. PO injection led to the inflammation of kidney tissues, and OJ improved it significantly. 4. The activity of XO after PO injection was significantly increased, and allopurinol significantly inhibited XO activity in the liver. Conclusion: In the hyperuricemia rat model, OJ extract reduced uric acid concentration and demonstrated its anti-inflammatory effects. Thus, OJ extracts can be used to lower uric acid levels.