Xanthine Oxidase Enzyme Inhibitors Research Articles

Drug-Drug Interaction of Aldehyde Oxidase Inhibitor and Xanthine Oxidase Inhibitor with Favipiravir

Aim: Favipiravir is an effective antiviral used in the treatment of COVID-19. It is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug-drug interactions between favipiravir with both AO substrate and XO enzyme inhibitor, allopurinol, and an XO inhibitor, verapamil. 
 Material and Methods: 25 Sprague-Dawley female rats, 250-300 g, were divided into five equal groups. Blood samples were taken from the jugular vein at the end of 0, 15, 30, and 45 minutes, and at the end of the 1st, 2nd, 4th, 6th, and 8th hours after the drugs were administered. The drug-blood concentration was determined in the HPLC-UV device using plasma. The ELISA method measured AO and XO enzyme activities in rat liver tissue.
 Results: Allopurinol prolonged the time taken for favipiravir to reach Cmax (Tmax), decreased maximum serum concentration (Cmax), elimination half-life (T1/2), area under the curve (AUC), and mean residence time (MRT). Allopurinol significantly reduced clearance per unit time (Cl/f) when co-administered with favipiravir. Verapamil accelerated the elimination of favipiravir, significantly reducing T1/2, MRT, and AUC. On the other hand, Favipiravir decreased the absorption of verapamil and slowed its elimination. Cmax, AUC, and Cl values of verapamil decreased. In addition, T1/2, MRT, and volume of distribution (Vd) increased. 
 Conclusion: In conclusion, the concomitant use of favipiravir with other drugs that affect AO and/or XO enzyme activities may cause changes in the pharmacokinetic profiles of drugs and the levels of enzymes that metabolize drugs.

Flavonoid isolation and identification of mother-in-law’s tongue leaves (sansevieria trifasciata) and the inhibitory activities to xanthine oxidase enzyme

Hyperuricemia is a disease that is characterized by high uric acid levels, in which the number of victim increase year by year in the worldwide. Flavonoid is an active compound with inhibitory activity towards Xanthine Oxidase Enzyme which is a compound that plays a role in the formation of uric acid in the body.Sansevieria trifasciatais an ornamental plant which is also useful as a source of antibacterial and antioxidant agent. Studies of S.trifasciataas Xanthine Oxidase Enzyme inhibitor have not been reported. This research isolate flavonoid compounds using open column chromatography from crude extract of S.trifasciataleaves that extracted by sonication method. There are six eluent used to isolate flavonoid which are methanol : ethyl acetate, chloroform : ethyl acetate, chloroform : ethyl acetate : methanol. Wilstater test is used to select the fraction that rich of flavonoid. The best result from isolation step that contains flavonoid is assessed the inhibitory activity of xanthine oxidase. It is analyzed qualitative using Liquid Chromatography Mass Spectrometry (LCMS). The inhibition percentage showed that fraction 3 was potential to inhibit XO by 85.48 %. LC-MS chromatogram can show that crude extract and positive fraction of isolation were containing falvonoid.

Gold‐NHC complexes as potent bioactive compounds

AbstractThis report describes the evaluation of the biological activities of 13 gold‐NHC complexes. These complexes were evaluated in vitro for their antioxidant properties, α‐glucosidase, thymidine phosphorylase, β‐glucuronidase and xanthine oxidase enzyme inhibition activities. Among the tested complexes, those bearing chloride ligands were found to be potent antioxidant, α‐glucosidase, thymidine phosphorylase, β‐glucuronidase and xanthine oxidase enzyme inhibitors, showing several hundred fold higher activity than the standard drugs. Some of these complexes were found to be potent antileishmanial agents, which were superior to standard antileishmanil drugs. These gold complexes were also evaluated for their in vitro cytotoxic activity against PC‐3 (normal cells), HeLa (cervical cancer), MCF‐3 (breast cancer) and 3T3 (mouse fibroblast) cell lines.

Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine

Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10mg/kg fluoxetine, 50mg/kg allopurinol, 50mg/kg allopurinol+10 mg/kg fluoxetine; n=8 per group), and forced swimming tests were performed before and after 14days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy.

Novel C-9, 9'-O-acyl Esters of (-)-Carinol as Free-radical Scavengers and Xanthine Oxidase Enzyme Inhibitors: Synthesis and Biological Evaluation

New compounds with hydrophyllic esters of (-)-carinol were synthesized and evaluated as xanthine oxidase enzyme inhibitors and antioxidants. Aliphatic esterfication of C-9,9'-OH groups of (-)-carinol resulted in lowering antioxidant and xanthine oxidase inhibitory activities. However certain aromatic acyl esters considerably improved the xathine oxidase inhibition. Aromatic esterification with electron withdrawing substitutions would preferred for improvement in XOD inhibition while retaining radical scavenging activity, electron withdrawing substitution led to the loss of free radical scavenging property and neutral substituents decrease the enzyme inhibitory potential.

Novel C-9, 9'-O-acyl Esters of (-)-Carinol as Free-radical Scavengers and Xanthine Oxidase Enzyme Inhibitors: Synthesis and Biological Evaluation

New compounds with hydrophyllic esters of (-)-carinol were synthesized and evaluated as xanthine oxidase enzyme inhibitors and antioxidants. Aliphatic esterfication of C-9,9'-OH groups of (-)-carinol resulted in lowering antioxidant and xanthine oxidase inhibitory activities. However certain aromatic acyl esters considerably improved the xathine oxidase inhibition. Aromatic esterification with electron withdrawing substitutions would preferred for improvement in XOD inhibition while retaining radical scavenging activity, electron withdrawing substitution led to the loss of free radical scavenging property and neutral substituents decrease the enzyme inhibitory potential. Keywords: (-)-Carinol, Acyl derivatives, Xanthine oxidase inhibition, Free radical scavenging activity

Investigation of the Oxidative Effect of Chronic Hyperammonemia on the Kidney and the Possible Protective Effect of Allopurinol

Although there have been many studies on this topic, the molecular mechanism of the toxic effects of hyperammonemia on cells has not yet been fully explained. Recent studies have held oxidative stress mechanisms responsible for hyperammonemia-induced cell damage. Kidney functions are affected in diseases associated with an increase in ammonia in the blood. Our study tries to determine whether oxidative stress mechanisms are responsible for kidney damage in chronic hyperammonemia. We also investigated whether kidney damage is dependent on possible reactive oxygen products associated with the xanthine oxidase (XO) enzyme and whether the possible association can be inhibited with allopurinol, an XO enzyme inhibitor. The study took into consideration the enzyme activities of XO, xanthine dehydrogenase (XDH), superoxide dismutase (SOD), glutathione-S-transferase (GST), as well as protein thiol (P–SH) and malondialdehyde (MDA) levels. The data found demonstrated that chronic hyperammonemia had oxidative stress effects on the kidney, and that kidney XO and XDH activity changed. However, it was not possible to inhibit this oxidative stress in the kidney using allopurinol. Thus, we could not conclude that oxidative stress is an XO‐dependent mechanism. The outcomes of the study suggested that this oxidative situation arising in hyperammonemia occurred through a mechanism other than the XO enzyme.

The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models.

Recent experimental work has suggested that oxygen-derived free radicals may play an important role in initiating the early capillary injury in acute pancreatitis. Data from models of ischemic injury in other organs have suggested the enzyme xanthine oxidase is important in generating oxygen-derived free radicals. The present study was performed to determine whether xanthine oxidase is the source of free radical production in experimental pancreatitis. Utilizing the isolated, perfused, ex vivo canine pancreas preparation, three models of pancreatitis were initiated with (1) free fatty acid infusion (FFA), (2) partial duct obstruction and secretin stimulation (POSS), and (3) ischemia (ISCH). In each model, during a 4-hour perfusion, edema developed, weight gain occurred (FFA 120.6 +/- 21.1 gm; POSS 44.5 +/- 6.9 gm; ISCH 63.3 +/- 14.0 gm), and the serum amylase became elevated (FFA 1827 +/- 397 u/dl; POSS 10,171 +/- 1487 u/dl; ISCH 1860 +/- 365 u/dl). When the xanthine oxidase enzyme inhibitor allopurinol was added to the perfusate prior to the 4-hour perfusion, edema formation was absent or minimal, weight gain was significantly less (FFA 15.2 +/- 2.5 gm p less than 0.05; POSS 8.8 +/- 2.7 gm p less than 0.001; ISCH 12.3 +/- 2.8 gm p less than 0.01), and the amylase remained normal or the elevation was significantly decreased (FFA 996 +/- 189 u/dl p less than 0.05; POSS 3021 +/- 1074 u/dl p less than 0.001; ISCH 993 +/- 214 u/dl p less than 0.002). These data confirm that oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis, and suggest that the enzyme xanthine oxidase may well be the source of their production.