Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral drug, acyclovir, has been used in the treatment of chronic type B hepatitis. High serum concentrations of acyclovir are required to achieve inhibition of hepatitis B viral replication. Because only 15 to 20% of an oral dose is absorbed, it is necessary to administer acyclovir by intravenous infusion. 6-Deoxyacyclovir, an analog of acyclovir, is well absorbed when given orally, and is converted to acyclovir by xanthine oxidase which is present in the gut and liver. This study has examined the hepatic disposition of 6-deoxyacyclovir in a 100 ml recirculating (12 ml per min) perfused rat liver system. Following administration of a bolus dose of 5 mumoles 6-deoxyacyclovir to the reservoir, perfusate concentrations of 6-deoxyacyclovir declined monoexponentially, as the metabolite acyclovir appeared in the perfusate. Addition of the xanthine oxidase inhibitor allopurinol (5 mg) to the perfusate reservoir prior to the administration of 6-deoxyacyclovir resulted in impaired hepatic metabolism of 6-deoxyacyclovir, as demonstrated by a 47% reduction in systemic clearance rate (4.5 +/- 0.4 to 2.4 +/- 0.9 ml per min; p less than 0.05) (mean +/- S.E., n = 6) and a 1.8-fold increase in terminal elimination half-life of 6-deoxyacyclovir (23.5 +/- 2.7 to 42.7 +/- 4.1 min; p less than 0.05), accompanied by a 30% reduction in appearance of acyclovir. The efficient hepatic conversion of 6-deoxyacyclovir to the active antiviral drug, acyclovir, provides a rationale for trials of oral 6-deoxyacyclovir in the treatment of chronic type B hepatitis.
 ...
PMID:The disposition of 6-deoxyacyclovir, a xanthine oxidase-activated prodrug of acyclovir, in the isolated perfused rat liver. 355 15

(-)-beta-D-2-Aminopurine dioxolane (APD) and (-)-beta-D-2-amino-6-chloropurine dioxolane (ACPD) are recently synthesized dioxolanylpurine nucleoside derivatives being developed as potential prodrugs for the antiviral nucleoside analog (-)-beta-D-dioxolane guanine (DXG). In vitro, APD and ACPD are converted to DXG by xanthine oxidase and adenosine deaminase, respectively. The purpose of this study was to evaluate the preclinical pharmacokinetics of APD and ACPD and their potential for generating sustained levels of the parent nucleoside, DXG, in rhesus monkeys following oral administration. Both nucleoside derivatives were rapidly absorbed, with similar peak concentrations achieved within 1 h after administration. However, concentrations of APD were more markedly sustained than those of ACPD. Both prodrugs yielded DXG, but significantly higher serum concentrations of DXG and area under the concentration-time curve values were observed following administration of APD. In addition, APD produced higher concentrations of prodrug and DXG in cerebrospinal fluid than did ACPD. Thus, the results of this pharmacokinetic study suggest that APD is likely to serve as a better prodrug of DXG and should be considered for clinical trials for antiviral therapy against human immunodeficiency virus and hepatitis B virus.
 ...
PMID:Pharmacokinetics of (-)-beta-D-2-aminopurine dioxolane and (-)-beta-D-2-amino-6-chloropurine dioxolane and their antiviral metabolite (-)-beta-D-dioxolane guanine in rhesus monkeys. 889 Nov 40

9-(beta-D-1,3-Dioxolan-4-yl)guanine (DXG) exhibits potent antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) in vitro. However, since DXG possesses limited aqueous solubility, a more water soluble prodrug of DXG, 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine (APD), was synthesized. The purpose of this study was to characterize the pharmacokinetics of APD and its antiviral metabolite DXG in mice. Female NIH-Swiss mice were administered 100 mg/kg APD intravenously or orally. Serum, brain and liver were collected at selected times following prodrug administration and concentrations of APD and DXG were determined by HPLC. APD was efficiently converted to parent nucleoside DXG following both intravenous and oral administration. Biotransformation of APD to DXG likely occurs in the liver and is mediated by xanthine oxidase. Similar pharmacokinetic profiles for DXG were observed following either route of administration in serum, liver and brain. These results demonstrate that APD appears to be a promising prodrug for the delivery of DXG.
 ...
PMID:Biotransformation and pharmacokinetics of prodrug 9-(beta-D-1,3-dioxolan-4-yl)-2-aminopurine and its antiviral metabolite 9-(beta-D-1,3-dioxolan-4-yl)guanine in mice. 929 58

A novel flow-injection chemiluminescence-based method has been developed for determination of superoxide dismutase (SOD) activity. An in-vitro superoxide anion generation xanthine/xanthine oxidase stable source was established on line with FIA/CL-detection apparatus, for measuring SOD activity. This method can detect SOD in the linear range of 0.002-2.00 U mL(-1) with a detection limit of 0.001 U mL(-1). Another method for detection of superoxide anion is based on the luminol-FeCl(3) chemiluminescence (CL) reaction. This method was used to evaluate superoxide release and SOD activity in rats treated with the traditional Chinese herb Pulsatilla chinensis, which resulted in high clearance of hepatitis B virus (HBV) after treatment of a hepatitis B patient. Interestingly, we found that treatment with Pulsatilla chinensis can specifically increase superoxide release by liver tissues and, at the same time, slightly increase extracellular SOD (ECSOD) activity in plasma; in particular it can markedly increase MnSOD activity in mitochondria in liver tissue. This work revealed a possible mechanism whereby Pulsatilla chinensis prevents possible infection (for example HBV) by specifically increasing superoxide release in the liver and increasing MnSOD activity to minimize superoxide-mediated toxicity.
 ...
PMID:Chemiluminescence detection of superoxide anion release and superoxide dismutase activity: modulation effect of Pulsatilla chinensis. 1498 8

Four flavone compounds were isolated from the effective fractions inhibiting xanthine oxidase (XOD) of the medicinal plant Selaginella labordei with anti-virus activity, and the structures were elucidated as 4'-methylether robustaflavone (1), robustaflavone (2), eriodictyol (3) and amentoflavone (4). The 50% inhibitory concentration (IC(50)) of the three compounds of inhibiting XOD were 61.0, 0.199, 16.0 and 32.0 mg L(-1), respectively. All of these compounds were isolated from the species for the first time, and eriodictyol was found from Selaginellaceae for the first time. Among these compounds, robustaflavone has been reported as an effective compound against the hepatitis B virus.
 ...
PMID:Bioactive compounds of inhibiting xanthine oxidase from Selaginella labordei. 1929 80

Synthesis of 6-deoxycyclopropavir (10), a prodrug of cyclopropavir (1) and its in vitro and in vivo antiviral activity is described. 2-Amino-6-chloropurine methylenecyclopropane 13 was transformed to its 6-iodo derivative 14 which was reduced to prodrug 10. It is converted to cyclopropavir (1) by the action of xanthine oxidase and this reaction can also occur in vivo. Compound 10 lacked significant in vitro activity against human cytomegalovirus (HCMV), human herpes virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus type 1 (HIV-1), human hepatitis B virus (HBV), Epstein-Barr virus (EBV), vaccinia virus and cowpox virus. In contrast, prodrug 10 given orally was as active as cyclopropavir (1) reported previously [Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. et al. Antimicrob. Agents Chemother. 2004, 48, 4745] against murine cytomegalovirus (MCMV) infection in mice and against HCMV in severe combined immunodeficient (SCID) mice.
 ...
PMID:Synthesis and antiviral activity of 6-deoxycyclopropavir, a new prodrug of cyclopropavir. 2241 49

Type I interferon receptor (IFNAR) has been involved in the progression of chronic hepatitis B (CHB). Oxidative stress is also associated with hepatitis B virus (HBV) infection and might contribute to the structure and function of protein synthesis including the IFNAR family. This study was aimed to determine the possible associations between oxidative stress and peripheral IFNAR expression in chronic HBV infection. Fifty-four CHB patients and 31 liver cirrhosis (LC) patients were consecutively collected, as well as 11 healthy subjects as controls. Expression levels of IFNAR1 and IFNAR2 in peripheral blood lymphocytes and monocytes were measured by flow cytometry. IFNAR1 and IFNAR2c mRNA were detected by real-time reverse transcription-polymerase chain reaction. Levels of plasma-soluble IFNAR and oxidative stress parameters, including xanthine oxidase (XOD), malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) were detected by enzyme linked immunosorbent assay (ELISA). The frequencies of IFNAR1 and IFNAR2 in lymphocytes and monocytes were significantly increased in CHB and LC patients than in healthy controls. Expression levels of IFNAR1 and IFNAR2c mRNA and plasma-soluble IFNAR level in CHB and LC patients were upregulated compared with healthy controls. Mean fluorescence intensity (MFI) of IFNAR2 in monocytes of CHB patients was higher than that in LC patients. Levels of plasma XOD, MDA, and GST were significantly increased in CHB and LC patients compared with healthy controls. Meanwhile, GSH and GSH-Px in CHB and LC patients were decreased than that in healthy controls. Furthermore, plasma MDA, GSH, and GST levels in CHB patients were higher than that in LC patients. In CHB patients, plasma GST level was negatively correlated with MFI of IFNAR2 in lymphocytes. Our results suggested that oxidative stress play an important role in the regulation of IFNAR in chronic HBV infection.
...
PMID:Peripheral type I interferon receptor correlated with oxidative stress in chronic hepatitis B virus infection. 2366 46