• 통합자연과학논문집
• /
• 제8권4호
• /
• pp.258-266
• /
• 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.

• 사상체질의학회지
• /
• 제13권1호
• /
• pp.88-96
• /
• 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.

• 대한의생명과학회지
• /
• 제8권1호
• /
• pp.47-52
• /
• 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.

• 한국가축번식학회지
• /
• 제26권3호
• /
• pp.263-273
• /
• 2002

본 연구는 xanthine-xanthine oxidase system하에서 돼지 동결-융해 정자의 lipid peroxidation과 체외수정능력에 대한 $\beta$-mercaptoethanol ($\beta$-ME)의 영향을 검토하였다. 그 결과 돼지 동결-응해 정자가 X-XO system하에서 처리되었을 때, control구에서 높은 정자생존율이 관찰되었으나 처리구간의 유의차는 인정되지 않았다. 또한 첨체반응이 유기된 정자의 비율은 모든 처리구에서 $\beta$-ME 첨가시 보다 무첨가시가 유의적(P<0.05)으로 더 높았다. 한편, X-XO system하에서 체외수정시 난자에 대한 정자의 침입율은 모든 조건하에서 $\beta$-ME 첨가시가 무첨가시 보다 높은 경향을 나타냈지만, 유의적인 차이는 인정되지 않았다. 정자의 lipid peroxidation은 malondialdehyde (MDA)의 생성에 기초를 두고 평가하였는데, 모든 조건하에서 $\beta$-ME 첨가시 보다 무첨가시에 MDA의 생성이 높게 나타났지만, 유의적인 차이는 인정되지 않았다. 또한 동결-융해된 정자의 sulfhydryl (-SH) group의 함량을 측정한 결과 모든 처리구에서 $\beta$-ME 무첨가시 보다 첨가시에 높은 함량이 측정되었지만, 유의적인 차이는 인정되지 않았다. 한편, 체외에서 성숙시킨 난자의 투명대에 대한 동결-융해 정자의 접착 정도를 평가한 결과 모든 처리구에서 $\beta$-ME 첨가시 무 첨가시에 비해 다소 높은 경향을 보였으며, Control group의 경우 X+XO group에 비해 유의적(P<0.05)으로 높은 정자접착율이 관찰되었다 그렇지만, $\beta$-ME 첨가 유무에 따를 유의적인 차이는 인정되지 않았다. 된 연구의 결과는 X-XO system하에서 $\beta$-ME 첨가가 돼지에서의 체외수정능력 향상에 영향을 미치는 것으로 생각된다.

• 동의생리병리학회지
• /
• 제16권3호
• /
• pp.553-556
• /
• 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.

• 동의생리병리학회지
• /
• 제17권2호
• /
• pp.549-552
• /
• 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.

• 동의생리병리학회지
• /
• 제17권2호
• /
• pp.443-446
• /
• 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
• /
• 제31권1호
• /
• pp.37-47
• /
• 2001

화상에 의한 피부 손상이 간에 미치는 영향을 알아보기 위하여 흰쥐를 이용하여 피부 화상을 유도한 다음 각각 5시간, 24시간 후 생화학적 정량법과 형태학적 관찰을 통해 간 조직 손상의 발병기전을 검토해 보고자 하였다. 흰쥐의 화상 유발은 등쪽면의 털을 깎고(total burn surface area $20\sim25%$) $100^{\circ}C$ 물로 10초간 흡입손상 없이 피부 화상만을 가하였다. 생화학적 정량으로는 혈청 내 xanthine oxidase(XO)와 aniline aminotransferase (ALT)의 활성변화, 그리고 혈장 단백질 함량 변화를 측정하였고, 형태학적 관찰은 혈액 중 다형핵 백혈구 수의 산정과 간 세포의 미세구조 변화를 관찰하였다. 실험 결과, 화상 후 혈청 내 XO의 활성 증가(P<0.01)와 함께 체중 당 간 무게(p<0.05)와 혈청 내 ALT의 활성이 증가되었다. 화상 직후 allopurinol의 복강투여로 XO활성, 간 무게, 그리고 ALT의 활성은 모두 감소되었다. 화상 손상에 의한 간 조직의 미세구조적 변화로는 소포체 종창, 리보솜 탈락, 지방소적의 축적, 그리고 담모세관과 세포간질의 확장이 관찰되었다. 뿐만 아니라 염증세포인 호중구의 침윤과 함께 혈관 내피세포의 손상, 쿠퍼세포의 활성화, 그리고 미세융모의 손상들이 관찰되었다. 또한 혈 중 다형핵 백혈구의 수적인 변화에서 화상 유발 5시간 후에 현저히 감소되어 내부 장기에 호중구 침윤의 가능성을 알 수 있었다. 하지만 allopurinol의 투여로 이러한 미세구조의 변화를 예방할 수 있는 것으로 나타났다. 이러한 결과들을 종합해 볼 때, 피부 화상으로부터 간 손상을 유발하는데 있어서 혈 중 XO의 활성증가가 매우 핵심적인 역할을 담당하는 것으로 사료되었다.

• Journal of Acupuncture Research
• /
• 제40권2호
• /
• pp.135-142
• /
• 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
• /
• 제40권1호
• /
• pp.53-60
• /
• 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.