A series of 8-substituted alkyl xanthines were evaluated in vitro to test the cytotoxocity in cells. For this experiment, we utilized different mammalian cancer cell lines primarily representing prostrate and lung. On...A series of 8-substituted alkyl xanthines were evaluated in vitro to test the cytotoxocity in cells. For this experiment, we utilized different mammalian cancer cell lines primarily representing prostrate and lung. One of the compounds synthesized, viz. 8-tertbutyl caffeine showed potent anticancer activity at low concentrations against DU145 when compared to adriamycin. Further experiments were carried out to check the cell cycle arrest in the DU145 cells treated with adriamycin, caffeine and 8-tert butyl caffeine. We observed that there was an arrest in G1 phase of cell cycle at 24 hours while at 48 hours of incubation, the cells were constantly distributed (59.71% -70.79%). We conclude that the effect of 8-tertbutyl caffeine is relatively comparable to caffeine whereas in adriamycin treated cells, we observed the cells underwent G2 arrest. We evaluate the studies on these effects by showing potent analogues which could be used as promising anticancer agents.展开更多
This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L....This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L.reuteri CCFM1132(n=34)or placebo(n=31)daily for 8 weeks.After the intervention,serum UA concentration significantly decreased,along with a reduction in xanthine oxidase(XOD)activity compared to the placebo group(P<0.01).Indicators of liver(aspartate transaminase and alanine transaminase)and renal(urea and creatinine)functions improved.Short-chain fatty acid(SCFA)concentrations significantly increased,with an upregulated abundance of SCFA producers(Fusicatenibacter,Ruminococcaceae UCG_014,and Ruminococcus 1)in the gut.Additionally,correlation analysis revealed that concentrations of SCFAs,particularly acetate and butyrate,were strongly negatively correlated with UA concentration and XOD activity.These findings suggest that L.reuteri CCFM1132 relieves hyperuricemia by enhancing the abundance of SCFA producers in the gut to promote SCFA production and by suppressing XOD activity.This study provides a valuable reference for developing new treatments for hyperuricemia.展开更多
Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering incre...Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.展开更多
Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is ...Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.展开更多
Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial...Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named(-) ethyl 1, 4-di-O-caffeoylquinate(1) and(-) methyl 1, 4-di-O-caffeoylquinate(2), together with 35 known compounds(3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1(IC_(50) 11.94 μmol·L^(-1)) and 2(IC_(50) 15.04 μmol·L^(-1)) showed a good inhibitory activity. The current results supported the medical use of the plant.展开更多
Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged b...Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.展开更多
Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In this in vitro study, Kinetic measurements wer...Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In 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. Results Four potent xanthine oxidase inhibitors were found in 95% ethanolic(v/v) Gnaphalium affine extract. Among them, the f lavone 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. Conclusions These 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.展开更多
OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were g...OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.展开更多
A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1...A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1 was elucidated on the basis of spectral analysis including 1D and 2D NMR and HR-ESI-MS.Saponins 1 and 4 exhibited significant XOD inhibitory activity in the test.展开更多
Objective: To screen Vietnamese medicinal plants for xanthine oxidase(XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. Methods: The plants materials were extracted by methanol. The ac...Objective: To screen Vietnamese medicinal plants for xanthine oxidase(XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. Methods: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. Results: Three hundreds and eleven methanol extracts(CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 μg/m L with inhibition rates of over 50%. The extracts of Archidendron clypearia, Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC_(50) values below 30 μg/m L. Chemical study performed on the extract of Archidendron clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and(-)-7-O-galloyltricetiflavan. The compound(-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC_(50) value of 25.5 μmol/L. Conclusions: From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC_(50) values of the methanol extracts below 30 μg/m L. Compound(-)-7-O-galloyltricetiflavan was identified as an XO inhibitor from Archidendron clypearia with IC_(50) value of 25.5 μmol/L.展开更多
AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in...AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.展开更多
Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in...Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography （RP-HPLC） with ultraviolet （UV） detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 （5：95）. Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957-0.9993. The proposed analytical method has satisfactory repeatability （the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49-97.90%, 95.38-96.45%, 112.46-115.78%and 90.82-97.13%with standard deviation of o5%, respectively） and the limits of detection （LODs, S/N Z 3） for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis＇ biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis.展开更多
OBJECTIVE: To investigate the effects of needling the Shu, Yuan, and Mu acupoints on serum uric acid(SUA), xanthine oxidase(XOD), and alkaline phosphatase(ALP) levels and the kidney index in a rat model of gout and hy...OBJECTIVE: To investigate the effects of needling the Shu, Yuan, and Mu acupoints on serum uric acid(SUA), xanthine oxidase(XOD), and alkaline phosphatase(ALP) levels and the kidney index in a rat model of gout and hyperuricemia.METHODS: Fifty rats were randomly divided into five groups: blank, model, Shu-acupoint, Yuan-acupoint, and Mu-acupoint groups. A rat model of hyperuricemia was developed by intragastric administration of adenine and ethambutol. This experiment last for 90 d in total. Treatment groups underwent 3 courses of acupuncture. Each course involved a total of 10 interventions(one intervention every second day) with each intervention lasting15 min. There was a break for 10 d between courses. SUA and ALP were analyzed using an automatic biochemical analyzer and XOD was analyzed using immunofluorescence.RESULTS: Compared with the blank group, SUA and XOD levels in the model group were significantly higher and the renal index significantly improved. Compared with the model group, SUA and XOD levels in the three treatment groups decreased and the renal index significantly improved.When the three treatment groups were compared,the Mu-acupoint group showed the greatest decreases in SUA and XOD levels, followed by the Yuan-acupoint group. There was no significant difference in kidney index among the three treatment groups. There was no significant difference in ALP levels among the groups.CONCLUSION: The three treatments showed significantly reduced SUA and XOD levels compared with the control groups, possibly suggesting reduced renal damage.展开更多
Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine deh...Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1(esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism.Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence.These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.展开更多
The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that t...The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions,2 salt bridges,5 conventional hydrogen bond interactions,and 4 attractive charge interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.展开更多
Objective:To evaluate in vitro antioxidant and apoptotic activities of Crperus rotundas(C.rotundus).Methods:The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C.rotundus ...Objective:To evaluate in vitro antioxidant and apoptotic activities of Crperus rotundas(C.rotundus).Methods:The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C.rotundus aerial part were determined.In addition,these extracts were also investigated for their cytotoxic and apoptotic activities.The major compound of the methanol extract was isolated.Both metlianol and aqueous extracts(300,150,and 50μg/mL)were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system.However,16,8,and 4 mg/mL of each extract were tested to investigate their OH.formation scavenging potential.Aqueous extract(800,400.and 200μg/mL)and melhunol extract(350,175,and 88μg/mL)were tested against lipid peroxidation,induced by 75μM H_2O_2,The cytotoxicity(by MTT assay)and cell DNA fragmentation of both extracts were evaluated Inwards K562 and L1210 cell lines.The major compound was obtained from the butanol fraction of methanol extract and its structure was determined by KMN spectroscopic analysis.Results:The methanol and aqueous extracts showed respectively,88%and 19%inhibition of xanthine oxidase activity.Vet.the same extracts inhibited lipid peroxidation by 61.5%and 42.0%.respectively.Roth extracts inhibited OH.formation by 27.1%and 25.3%,respectively.Only methanol cxtract induced DNA degradation.Orientin was determined as the major compound isolated from the butanol fraction of metlianol extract.Conclusions:It appears that C.rotundus extracts exhibit a potential use as a natural antioxidant and an apoptosis inducer.展开更多
A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid（UA）,xanthine（XA）,hypoxanthine（HX） and dop...A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid（UA）,xanthine（XA）,hypoxanthine（HX） and dopamine（DA）.This new electrode presented an excellent electrocatalytic activity towards the oxidation of UA,XA,HX and DA by cyclic voltammetry（CV） method.The oxidation peaks of the four compounds were well defined and had the enhanced peak currents.The separation potentials of the oxidation peaks for DA-UA,UA-XA and XA-HX were 150,390 and 360 mV in CV,respectively.By means of differential pulse voltammetry（DPV） method,the calibration curves in the ranges of 10―225,5―105,10―170 and 5―150 μmol/L were obtained for UA,XA,HX and DA,respectively.The lowest detection limits（S/N=3） were 5,1.25,5 and 1.5 μmol/L for UA,XA,HX and DA,respectively.The practical application of the modified electrode was demonstrated by the determination of DA in hydrochloride injection and UA,XA,HX in human urine samples.展开更多
In recent years, lipid peroxidation has been considered as the initial step for foreign toxic substances to damage cells. In this paper, the effects of methylmercury (MeHg) on LPO (lipid peroxide) levels, SH (sulfhydr...In recent years, lipid peroxidation has been considered as the initial step for foreign toxic substances to damage cells. In this paper, the effects of methylmercury (MeHg) on LPO (lipid peroxide) levels, SH (sulfhydryl) groups and activities of GSH\|Px (glutathione peroxidase), SOD (superoxide dismutase), XOD (xanthine oxidase) in liver of rats treated with doses of MeHg at different intervals were studied by TBA, Ellman Reagent, NBT colorimetric methods and chemilluminescence. Meanwhile, the contents of FR (free radical)and MeHg in the liver of female rats were measured by ESR and GC. Results showed that the LPO levels in the experimental group increased significantly over those of the control group ( p<0.05— p<0.001) , reaching maximum point on the first poisoning day. Both male and female rats showed marked positive dose\|effect relations (Male: Y=261.4±49.4X, r=0.94, p<0.02; Female : Y=255.0±73.0X, r=0.99, p<0.001 ). N-SH (nonprotein sulfhydryl), P\|SH (protein sulfhydryl), T-SH (total sulfhydryl) contents and GSH\|Px activities decreased significantly (p<0.05-p<0.001). For GSH\|Px, both groups reached minimum value on the first poisoning day. In female rats, activities of SOD and XOD increased markedly ( p<0.02-p<0.01 ) although the contents of FR showed no significant changes. The contents of MeHg was determined by GC, and it ranged from 0.0081—0.0191 ppm.展开更多
Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febu...Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP)and the mechanisms by which it acts.Methods Twenty-four rabbits were randomly divided into four groups:sham-operated group(Group S),RAP group(Group P),RAP with 5 mg/kg per day febuxostat group(Group LFP),and RAP with 10 mg/kg per day febuxostat group(Group HFP).All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks.The effects of febuxostat on atrial electrical and structural remodeling,markers of inflammation and oxidative stress,and signaling pathways involved in the left atrium were examined.Results Shortened atrial effective refractory period(AERP),increased AF inducibility,decreased mRNA levels of Cav1.2 and Kv4.3,and left atrial enlargement and dysfunction were observed in Group P,and these changes were suppressed in the groups treated with febuxostat.Prominent atrial fibrosis was observed in Group P,as were increased levels of TGF-β1,Collagen I,andα-SMA and decreased levels of Smad7 and eNOS.Treatment with febuxostat attenuated these differences.Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat.Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.展开更多
This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the ...This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.展开更多
文摘A series of 8-substituted alkyl xanthines were evaluated in vitro to test the cytotoxocity in cells. For this experiment, we utilized different mammalian cancer cell lines primarily representing prostrate and lung. One of the compounds synthesized, viz. 8-tertbutyl caffeine showed potent anticancer activity at low concentrations against DU145 when compared to adriamycin. Further experiments were carried out to check the cell cycle arrest in the DU145 cells treated with adriamycin, caffeine and 8-tert butyl caffeine. We observed that there was an arrest in G1 phase of cell cycle at 24 hours while at 48 hours of incubation, the cells were constantly distributed (59.71% -70.79%). We conclude that the effect of 8-tertbutyl caffeine is relatively comparable to caffeine whereas in adriamycin treated cells, we observed the cells underwent G2 arrest. We evaluate the studies on these effects by showing potent analogues which could be used as promising anticancer agents.
基金supported by the National Natural Science Foundation of China(32272332,32021005)the Fundamental Research Funds for the Central Universities(JUSRP622020,JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province.
文摘This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L.reuteri CCFM1132(n=34)or placebo(n=31)daily for 8 weeks.After the intervention,serum UA concentration significantly decreased,along with a reduction in xanthine oxidase(XOD)activity compared to the placebo group(P<0.01).Indicators of liver(aspartate transaminase and alanine transaminase)and renal(urea and creatinine)functions improved.Short-chain fatty acid(SCFA)concentrations significantly increased,with an upregulated abundance of SCFA producers(Fusicatenibacter,Ruminococcaceae UCG_014,and Ruminococcus 1)in the gut.Additionally,correlation analysis revealed that concentrations of SCFAs,particularly acetate and butyrate,were strongly negatively correlated with UA concentration and XOD activity.These findings suggest that L.reuteri CCFM1132 relieves hyperuricemia by enhancing the abundance of SCFA producers in the gut to promote SCFA production and by suppressing XOD activity.This study provides a valuable reference for developing new treatments for hyperuricemia.
基金funded by Vietnam National Foundation for Science and Technology Development under grant number 108.05-2023.23.
文摘Objective:To investigate the effects of a crude extract from Gnetum montanum Markgr.on ethanol-induced hepatotoxicity and metabolic disorders.Methods:Alcoholic liver disorder was induced in mice by administering increasing doses of ethanol via oral gavage.Biomarkers of liver injury and oxidative stress were assessed at the end of the study.Liver tissue damage and fat deposition were evaluated using hematoxylin and eosin and oil red O staining,respectively.In addition,key biomarkers were examined in acetaldehyde-treated HepG2 cells.Results:Ethanol consumption induced characteristic pathological changes,including elevated serum markers of liver injury,hepatic lipid accumulation,and oxidative stress in liver tissues.Oral administration of Gnetum montanum extract(175 and 350 mg/kg)decreased serum aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transferase,and bilirubin levels in ethanol-treated mice.The extract also lowered triglyceride levels in serum and liver tissue in a dose-dependent manner.Furthermore,it mitigated malondialdehyde levels,preserved reduced glutathione levels,and enhanced catalase activity and total antioxidant capacity in liver tissue homogenates.Additionally,ethanol-induced hyperuricemia was suppressed by Gnetum montanum extract by inhibiting xanthine oxidase activity.Similar effects were observed in Gnetum montanum extract-treated HepG2 cells.Conclusions:This study demonstrates that Gnetum montanum extract alleviates ethanol-induced hepatic injury by alleviating oxidative stress and inhibiting xanthine oxidase activity.
文摘Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.
基金supported by the Natural Science Foundation of Shanghai(No.15ZR1440100)the National Natural Science Foundation of China(No.81603279)
文摘Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named(-) ethyl 1, 4-di-O-caffeoylquinate(1) and(-) methyl 1, 4-di-O-caffeoylquinate(2), together with 35 known compounds(3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1(IC_(50) 11.94 μmol·L^(-1)) and 2(IC_(50) 15.04 μmol·L^(-1)) showed a good inhibitory activity. The current results supported the medical use of the plant.
基金supported by the Natural Science Foundation of China(No.NSFC.30670415).
文摘Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine （XA）/xanthine oxidase （XO）-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.
文摘Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In 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. Results Four potent xanthine oxidase inhibitors were found in 95% ethanolic(v/v) Gnaphalium affine extract. Among them, the f lavone 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. Conclusions These 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.
基金Supported by the National Natural Sciences Foundation of China(A Study on the Anti-gout Effects and Related Mechanisms of Tibetan Medicine Rupeng15 Powder,No.81160410)
文摘OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.
基金financially supported by the Postgraduate Innovation Project of Jiangsu Province,China(No. CX09B_284Z)
文摘A new triterpene saponin with 28-nor-urs-12（13）,18（17）-dien-3β-ol as aglycone,named ilexsaponin C（1） was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1 was elucidated on the basis of spectral analysis including 1D and 2D NMR and HR-ESI-MS.Saponins 1 and 4 exhibited significant XOD inhibitory activity in the test.
基金funded by Vietnam National Foundation for Science and Technology Development(NAFOSTED)under grant number 106.99-2012.90
文摘Objective: To screen Vietnamese medicinal plants for xanthine oxidase(XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. Methods: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. Results: Three hundreds and eleven methanol extracts(CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 μg/m L with inhibition rates of over 50%. The extracts of Archidendron clypearia, Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC_(50) values below 30 μg/m L. Chemical study performed on the extract of Archidendron clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and(-)-7-O-galloyltricetiflavan. The compound(-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC_(50) value of 25.5 μmol/L. Conclusions: From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC_(50) values of the methanol extracts below 30 μg/m L. Compound(-)-7-O-galloyltricetiflavan was identified as an XO inhibitor from Archidendron clypearia with IC_(50) value of 25.5 μmol/L.
基金The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), DK069939 the Technology Transfer Grant (TTG) by UC Davis Medical Center to Wu J
文摘AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.
基金supported by the National Natural Science Foundation of China(No.21275088)
文摘Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography （RP-HPLC） with ultraviolet （UV） detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 （5：95）. Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957-0.9993. The proposed analytical method has satisfactory repeatability （the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49-97.90%, 95.38-96.45%, 112.46-115.78%and 90.82-97.13%with standard deviation of o5%, respectively） and the limits of detection （LODs, S/N Z 3） for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis＇ biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis.
基金Supported by Central Universities Fundamental Research Funds Project(Graduate Programs)from the Beijing University of Chinese Medicine:Experiment Research on the Effects of Acupuncturing Shu,Yuan,and Mu Acupoints in a Rat Model of Gout and Hyperuricemia(No.2015-JYB-XS127)
文摘OBJECTIVE: To investigate the effects of needling the Shu, Yuan, and Mu acupoints on serum uric acid(SUA), xanthine oxidase(XOD), and alkaline phosphatase(ALP) levels and the kidney index in a rat model of gout and hyperuricemia.METHODS: Fifty rats were randomly divided into five groups: blank, model, Shu-acupoint, Yuan-acupoint, and Mu-acupoint groups. A rat model of hyperuricemia was developed by intragastric administration of adenine and ethambutol. This experiment last for 90 d in total. Treatment groups underwent 3 courses of acupuncture. Each course involved a total of 10 interventions(one intervention every second day) with each intervention lasting15 min. There was a break for 10 d between courses. SUA and ALP were analyzed using an automatic biochemical analyzer and XOD was analyzed using immunofluorescence.RESULTS: Compared with the blank group, SUA and XOD levels in the model group were significantly higher and the renal index significantly improved. Compared with the model group, SUA and XOD levels in the three treatment groups decreased and the renal index significantly improved.When the three treatment groups were compared,the Mu-acupoint group showed the greatest decreases in SUA and XOD levels, followed by the Yuan-acupoint group. There was no significant difference in kidney index among the three treatment groups. There was no significant difference in ALP levels among the groups.CONCLUSION: The three treatments showed significantly reduced SUA and XOD levels compared with the control groups, possibly suggesting reduced renal damage.
基金supported by the Key Transgenic Breeding Program of the Ministry of Agriculture and Rural Affairs of China(2016ZX08009003-003-008)the National Natural Science Foundation of China(31971921,U20A2030)the State Key Laboratory of Rice Biology,China(20200102)。
文摘Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1(esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism.Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence.These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.
基金supported by Beijing Advanced Innovation Center for Food Nutrition and Human Health(20181036).
文摘The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions,2 salt bridges,5 conventional hydrogen bond interactions,and 4 attractive charge interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.
基金the "Ministere Francais des Affaires Etrangeres"(Action Integree de Cooperation Inter universitaire Franco-Tunisienne,PHC UTIQUE 07 G0836 PAR)the Ministry of Higher Education.Scientific Research and Technology in Tunisia for the financial assistance
文摘Objective:To evaluate in vitro antioxidant and apoptotic activities of Crperus rotundas(C.rotundus).Methods:The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C.rotundus aerial part were determined.In addition,these extracts were also investigated for their cytotoxic and apoptotic activities.The major compound of the methanol extract was isolated.Both metlianol and aqueous extracts(300,150,and 50μg/mL)were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system.However,16,8,and 4 mg/mL of each extract were tested to investigate their OH.formation scavenging potential.Aqueous extract(800,400.and 200μg/mL)and melhunol extract(350,175,and 88μg/mL)were tested against lipid peroxidation,induced by 75μM H_2O_2,The cytotoxicity(by MTT assay)and cell DNA fragmentation of both extracts were evaluated Inwards K562 and L1210 cell lines.The major compound was obtained from the butanol fraction of methanol extract and its structure was determined by KMN spectroscopic analysis.Results:The methanol and aqueous extracts showed respectively,88%and 19%inhibition of xanthine oxidase activity.Vet.the same extracts inhibited lipid peroxidation by 61.5%and 42.0%.respectively.Roth extracts inhibited OH.formation by 27.1%and 25.3%,respectively.Only methanol cxtract induced DNA degradation.Orientin was determined as the major compound isolated from the butanol fraction of metlianol extract.Conclusions:It appears that C.rotundus extracts exhibit a potential use as a natural antioxidant and an apoptosis inducer.
基金Supported by the Natural Science Foundation of Jilin Province,China(No.20090326)
文摘A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid（UA）,xanthine（XA）,hypoxanthine（HX） and dopamine（DA）.This new electrode presented an excellent electrocatalytic activity towards the oxidation of UA,XA,HX and DA by cyclic voltammetry（CV） method.The oxidation peaks of the four compounds were well defined and had the enhanced peak currents.The separation potentials of the oxidation peaks for DA-UA,UA-XA and XA-HX were 150,390 and 360 mV in CV,respectively.By means of differential pulse voltammetry（DPV） method,the calibration curves in the ranges of 10―225,5―105,10―170 and 5―150 μmol/L were obtained for UA,XA,HX and DA,respectively.The lowest detection limits（S/N=3） were 5,1.25,5 and 1.5 μmol/L for UA,XA,HX and DA,respectively.The practical application of the modified electrode was demonstrated by the determination of DA in hydrochloride injection and UA,XA,HX in human urine samples.
文摘In recent years, lipid peroxidation has been considered as the initial step for foreign toxic substances to damage cells. In this paper, the effects of methylmercury (MeHg) on LPO (lipid peroxide) levels, SH (sulfhydryl) groups and activities of GSH\|Px (glutathione peroxidase), SOD (superoxide dismutase), XOD (xanthine oxidase) in liver of rats treated with doses of MeHg at different intervals were studied by TBA, Ellman Reagent, NBT colorimetric methods and chemilluminescence. Meanwhile, the contents of FR (free radical)and MeHg in the liver of female rats were measured by ESR and GC. Results showed that the LPO levels in the experimental group increased significantly over those of the control group ( p<0.05— p<0.001) , reaching maximum point on the first poisoning day. Both male and female rats showed marked positive dose\|effect relations (Male: Y=261.4±49.4X, r=0.94, p<0.02; Female : Y=255.0±73.0X, r=0.99, p<0.001 ). N-SH (nonprotein sulfhydryl), P\|SH (protein sulfhydryl), T-SH (total sulfhydryl) contents and GSH\|Px activities decreased significantly (p<0.05-p<0.001). For GSH\|Px, both groups reached minimum value on the first poisoning day. In female rats, activities of SOD and XOD increased markedly ( p<0.02-p<0.01 ) although the contents of FR showed no significant changes. The contents of MeHg was determined by GC, and it ranged from 0.0081—0.0191 ppm.
基金supported by the Beijing Natural Science Foundation(Z141100002114050)
文摘Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP)and the mechanisms by which it acts.Methods Twenty-four rabbits were randomly divided into four groups:sham-operated group(Group S),RAP group(Group P),RAP with 5 mg/kg per day febuxostat group(Group LFP),and RAP with 10 mg/kg per day febuxostat group(Group HFP).All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks.The effects of febuxostat on atrial electrical and structural remodeling,markers of inflammation and oxidative stress,and signaling pathways involved in the left atrium were examined.Results Shortened atrial effective refractory period(AERP),increased AF inducibility,decreased mRNA levels of Cav1.2 and Kv4.3,and left atrial enlargement and dysfunction were observed in Group P,and these changes were suppressed in the groups treated with febuxostat.Prominent atrial fibrosis was observed in Group P,as were increased levels of TGF-β1,Collagen I,andα-SMA and decreased levels of Smad7 and eNOS.Treatment with febuxostat attenuated these differences.Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat.Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.
基金funded by the National Natural Science Foundation of China(21868003)the Guangxi Natural Science Foundation(2018AD19022,2017GXNSFAA198265)the Nanning Science and Technology Development Project(2017014).
文摘This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.
