- Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats. [Journal Article]
- BRBrain Res 2018 Feb 16
- Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/an...
Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete. Thus, the main aim of this study was the investigation of the effect of uric acid on absence epileptic seizures (spike-wave discharges: SWDs) in a model of human absence epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200 mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg) and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity. We demonstrated that both uric acid and allopurinol alone significantly increased the number of SWDs whereas indomethacin abolished the uric acid-evoked increase in SWD number. Our results suggest that uric acid and allopurinol have proepileptic effects in WAG/Rij rats.
- The vasodilatory effect of allopurinol mediates its antihypertensive effect: Effects on calcium movement and cardiac hemodynamics. [Journal Article]
- BPBiomed Pharmacother 2018 Feb 14; 100:381-387
- Despite the reported reduction in blood pressure in hypertensive patients treated with allopurinol, the mechanism of the allopurinol hypotensive effect is still unclear. In the current study, the hyp...
Despite the reported reduction in blood pressure in hypertensive patients treated with allopurinol, the mechanism of the allopurinol hypotensive effect is still unclear. In the current study, the hypotensive effect of allopurinol has been fully investigated in hypertensive rats. Hypertension was induced in rats by angiotensin II (120 ng/min/kg) infusion for two weeks. Rats were then subjected to real-time recording of blood pressure, left ventricular pressure and volume and surface ECG. After 10 min of basal recording, allopurinol was slowly injected into the femoral vein with a dose of 10 μmole/kg. Then, invasive blood pressure, cardiac hemodynamics and ECG were continuously recorded for an additional 20 min. In addition, the vasodilation effect of allopurinol was studied using the isolated artery technique. Allopurinol injection reduced systolic, diastolic and pulse blood pressure. Allopurinol suppressed both cardiac systolic and diastolic hemodynamics as is apparent from the reduction in the rate of rise and the rate of fall in left ventricular pressure. Allopurinol reduced the general cardiac output quickly. Allopurinol addition to the organ bath (10-1000 μM) produced significant vasodilation of PE pre-constricted aortae that was not affected by endothelium denudation, L-NAME or indomethacin. However, allopurinol ameliorated the calcium induced contraction of aorta pre-constricted with KCl in calcium-free media. Erk or ROCK inhibition did not attenuated allopurinol produced vasodilation. In conclusion, allopurinol has an antihypertensive effect that is mediated, probably, by reducing cardiac output and decreasing vascular resistance. The vasodilator effect of allopurinol is most likely mediated by calcium blocking activities.
- Management of gout by UK rheumatologists: a British Society for Rheumatology national audit. [Journal Article]
- RRheumatology (Oxford) 2018 Feb 13
- CONCLUSIONS: Gout management by UK rheumatologists concords well with guidelines for most audit standards. However, fewer than half of patients achieved a target serum uric level over 12 months. Rheumatologists should help ensure that ULT is optimized to achieve target serum uric acid levels to benefit patients.
- Immune cell response to strenuous resistive breathing: comparison with whole body exercise and the effects of antioxidants. [Journal Article]
- IJInt J Chron Obstruct Pulmon Dis 2018; 13:529-545
- CONCLUSIONS: We conclude that IRB produces (as WBE) changes in peripheral blood lymphocyte subsets and that oxidative stress is a major stimulus predominantly for IRB-induced lymphocyte subset alterations.
- Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia. [Journal Article]
- PlosPLoS One 2018; 13(2):e0192781
- CONCLUSIONS: Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions.
- Gout drugs use and risk of cancer: A case-control study. [Journal Article]
- JBJoint Bone Spine 2018 Feb 07
- CONCLUSIONS: In summary, our results suggest that gout drugs increase risk of the most common cancers, particularly in leukemia, non-Hodgkin's, endometrial, breast and cervical cancer.
- Xanthine oxidase inhibitors for prevention of cardiovascular events: a systematic review and meta-analysis of randomized controlled trials. [Journal Article]
- BCBMC Cardiovasc Disord 2018 02 07; 18(1):24
- CONCLUSIONS: Purine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (> 300 mg/day) may be associated with loss of CV protection.
- Hydrazine determination in allopurinol using derivatization and SPE for sample preparation. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Jan 26; 152:25-30
- Hydrazine is a useful building block in the synthesis of organic pharmaceuticals but it is highly toxic so its determination at low ppm range is required. In this work, hydrazine was determined in al...
Hydrazine is a useful building block in the synthesis of organic pharmaceuticals but it is highly toxic so its determination at low ppm range is required. In this work, hydrazine was determined in allopurinol active pharmaceutical ingredient (API) sample at 2.5 ppm level by using derivatization and solid phase extraction (SPE) followed by reversed phase liquid chromatography (RPLC). Hydrazine does not contain chromophore part and is not retained in RPLC thus derivatization was necessary for its determination. Benzaldehyde was found to be the most appropriate derivatization reagent so the analyzed solute was benzaldehyde azine, which had adequate UV absorption and could be retained in RPLC. The derivatization reaction was performed in 0.2 M NaOH solution/MeOH = 50/50 (v/v) mixture, which is a proper solvent for allopurinol, too. Because of the low detection limit, 50 mg sample had to be dissolved in 5 mL solvent. This is a very concentrated solution therefore column overload is expected. Using a C18 SPE for sample preparation allowed to get rid of the huge amount of allopurinol. As allopurinol has a more polar character than benzaldehyde azine, it was easy to wash out from the SPE phase. The benzaldehyde azine can be eluted with a strong solvent and then the eluted sample can be analyzed by RPLC. Limit test validation of the liquid chromatographic method has been performed as well. This complex but not complicated analysis can be used for the accurate determination of hydrazine in allopurinol API. Furthermore it is applicable for other APIs which are more polar than benzaldehyde azine and soluble in high concentration in the aqueous solvent.
- Association of non-immediate drug hypersensitivity with drug exposure: A case control analysis of spontaneous reports from a Tunisian pharmacovigilance database. [Journal Article]
- EJEur J Intern Med 2018 Feb 03
- CONCLUSIONS: Our findings corroborate risks for a number of drugs, such as antibacterials, antiepileptics and allopurinol in inducing DTCRs. Given the widespread use of these drug classes, awareness should be raised among patients and prescribers about these risks.
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- Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma. [Journal Article]
- JPJ Pharm Anal 2017; 7(1):56-62
- The present study describes a simple, reliable and reproducible liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous determination of allopurinol and its active metab...
The present study describes a simple, reliable and reproducible liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous determination of allopurinol and its active metabolite, oxypurinol in human plasma for a pharmacokinetic/bioequivalence study. After protein precipitation (PPT) of 100 µL plasma sample with 1.0% formic acid in acetonitrile, the recovery of the analytes and allopurinol-d2 as an internal standard ranged from 85.36% to 91.20%. The analytes were separated on Hypersil Gold (150 mm×4.6 mm, 5 µm) column using 0.1% formic acid-acetonitrile (98:2, v/v) as the mobile phase. Quantification was done using electrospray ionization in the positive mode. The calibration concentration range was established from 60.0 to 6000 ng/mL for allopurinol and 80.0-8000 ng/mL for oxypurinol. Matrix effect in human plasma, expressed as IS-normalized matrix factors ranged from 1.003 to 1.030 for both the analytes. The developed method was found suitable for a clinical study with 300 mg allopurinol tablet formulation in healthy subjects.