Allopurinol
[Effects of Rhizoma Ligustici chuanxiong and allopurinol on ischemia-reperfusion damage of rabbit ear flap]

[Article in Chinese]

Chen JW.

Changhai Hospital, Shanghai.

The effect of Rhizoma Ligustici Chuanxiong and allopurinol on ischemia-reperfusion damage of rabbit ear flap was studied. The results showed that MDA level was higher and SOD activity lower distinctly at 0.5 hour after reperfusion than that at 16 hours of postischemia and preischemia, Rhizoma Ligustici Chuanxiong and allopurinol changed the result markedly with a decrease of necrosis rate. The effect of Rhizoma Ligustici Chuanxiong was more significant than that of allopurinol in promoting microcirculation, preventing clot formation, reducing exudation and hemorrhage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8112166&dopt=Abstract allopurinol Zyloprim



Allopurinol
Hypouricemic effect of allopurinol and the novel xanthine oxidase inhibitor TEI-6720 in chimpanzees.

Komoriya K, Osada Y, Hasegawa M, Horiuchi H, Kondo S, Couch RC, Griffin TB.

Teijin Institute for Bio-medical Research, Tokyo, Japan.

The hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, was investigated and compared with that of allopurinol in male chimpanzees (n = 3). When allopurinol (10 mg/kg) was administered orally once a day for three consecutive days, it cumulatively reduced serum urate levels by 29.7, 50.1 and 60.2%, 24, 48 and 72 h, respectively, after the initial dose. This effect was dose dependent at doses of 3 and 10 mg/kg. At 3 mg/kg, the mean serum urate levels were 3.1, 2.4, 2.5 and 2.3 mg/dl before and 24, 48 and 72 h, respectively, after the initial dose. Animals treated with 10 mg/kg of allopurinol showed serum urate levels of 3.3, 2.3, 1.6 and 1.3 mg/dl, respectively. The urate-lowering effect of TEI-6720 was then compared with that of allopurinol at a daily dose of 5 mg/kg (n = 3). Both compounds caused striking reductions in serum and urinary uric acid levels accompanied by an increase in urinary xanthine levels. These effects of TEI-6720 were more potent than those of allopurinol. TEI-6720 reduced serum urate levels by 55.9, 69.6 and 73.6%, 24, 48 and 72 h, respectively, after the first dose, whereas the corresponding values after allopurinol were 28.1, 41.6 and 45.1%. These results suggest that the hypouricemic effect of TEI-6720 may be more potent than that of allopurinol in the treatment of hyperuricemia and gout, and that TEI-6720 may become an effective alternative drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8112406&dopt=Abstract allopurinol Zyloprim



Allopurinol
In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase.

Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K.

Third Department of Internal Medicine, Hyogo College of Medicine, Japan.

Aldehyde oxidase was purified about 120-fold from rat liver cytosol by sequential column chromatography using diethylaminoethyl (DEAE) cellulose, Benzamidine-Sepharose 6B and gel filtration. The purified enzyme was shown as a single band with M(r) of 2.7 x 10(5) on polyacrylamide gel electrophoresis (PAGE) and M(r) of 1.35 x 10(5) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using this purified enzyme, in vitro conversion of allopurinol, pyrazinamide and pyrazinoic acid was investigated. Allopurinol and pyrazinamide were oxidized to oxypurinol and 5-hydroxy-pyrazinamide, respectively, while pyrazinoic acid, the microsomal deamidation product of pyrazinamide, was not oxidized to 5-hydroxypyrazinoic acid. The apparent Km value of the enzyme for pyrazinamide was 160 microM and that for allopurinol was 1.1 mM. On PAGE, allopurinol- or pyrazinamide-stained band was coincident with Coomassie Brilliant Blue R 250-stained band, respectively. These results suggest that aldehyde oxidase may play a role in the oxidation of allopurinol to oxypurinol and that of pyrazinamide to 5-hydroxypyrazinamide with xanthine dehydrogenase which can oxidize both allopurinol and pyrazinamide in vivo. The aldehyde oxidase may also play a major role in the oxidation of allopurinol and pyrazinamide in the subgroup of xanthinuria patients (xanthine oxidase deficiency) who can oxidize both allopurinol and pyrazinamide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8216357&dopt=Abstract allopurinol Zyloprim



Allopurinol
Reperfusion arrhythmias and purine wash-out in isolated rat and rabbit heart. Effect of allopurinol, dimethylthiourea and calcium reduction.

Kopacz M, Karwatowska-Prokopczuk E, Beresewicz A.

Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.

The effects of perfusate calcium reduction, allopurinol and dimethylthiourea on reperfusion-induced arrhythmias and purine wash-out in isolated rabbit and rat hearts were compared. The overall incidence of reperfusion-induced ventricular tachycardia (VT) was 88% and 94% and that of ventricular fibrillation (VF) was 44% and 88% in the control rabbit and rat hearts, respectively. VF was reduced to 10% and 0% in rat and rabbit hearts subjected to perfusate calcium reduction (0.4 mM for 1 min before ischemia and for 1 min before and throughout reperfusion), respectively. In allopurinol, 1 mM, perfused rat hearts the overall incidence of VF was not changed and only the incidence of a sustained VF (that lasting for at least 10 min) was reduced. VT and VF were prevented in allopurinol-perfused rabbit hearts. Dimethylthiourea, 10 mM, reduced the incidence of VF in rat hearts to 16% and did not significantly affect VT and VF in rabbit hearts. In untreated rat hearts, the major purine compounds washed out upon reperfusion were inosine, hypoxanthine, xanthine and urate. Allopurinol augmented the wash-out of adenosine and abolished that of xanthine and urate. In untreated rabbit hearts, the major purine washed out were inosine, adenosine and hypoxanthine. Allopurinol did not cause further increase in adenosine wash-out in rabbit hearts. We speculate that: (1) calcium mediated arrhythmogenic mechanism is operating both in reperfused rat and rabbit heart; (2) free radical mediated mechanism is of an importance only in rat heart; (3) neither a decreased free radical production secondary to xanthine oxidase inhibition nor the augmentation of adenosine wash-out is a likely explanation for the antiarrhythmic effect of allopurinol in reperfused hearts; and (4) high level of myocardial adenosine accumulation during ischemia, probably secondary to low xanthine oxidase activity, may play a role of a natural defence mechanism in ischemic/reperfused rabbit heart.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8230246&dopt=Abstract allopurinol Zyloprim



Allopurinol
Age- and sex-related effects in German cockroaches fed an allopurinol diet (Dictyoptera: Blattellidae).

Suiter DR, Koehler PG, Patterson RS.

Department of Entomology and Nematology, University of Florida, Gainesville 32611-0740.

The effects of feeding several ages of adult and nymphal German cockroaches a laboratory rat chow diet containing 0.10% allopurinol were investigated. All cockroaches fed the allopurinol diet suffered increased mortality. The range of LT50 values (the time required to kill 50% of an experimental cohort) for four ages of nymphs (1-8, 16-23, 21-28, and 28-35 d old following hatch) continuously fed the allopurinol diet was 1.36 wk (4.72-6.08 wk). Regardless of sex, young adult (1-7 d old following eclosion) cockroaches fed the allopurinol diet died significantly sooner than older adults (28-35 d old following eclosion); males died significantly sooner than females. All females fed the allopurinol diet as nymphs aborted their oothecae. Although an initial ootheca were hatched from cockroaches fed the allopurinol diet as adults, all subsequent oothecae were aborted. Untreated females mated with allopurinol-fed males experienced successful reproduction, but allopurinol-fed females mated with either allopurinol- or control diet-fed males failed to reproduce. Evidence suggests that cockroaches suffer increased mortality and reproductive failure from increased levels of hypoxanthine and xanthine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8254639&dopt=Abstract allopurinol Zyloprim



Allopurinol
Superoxide dismutase and allopurinol improve survival in an animal model of hemorrhagic shock.

Tan LR, Waxman K, Clark L, Eloi L, Chhieng N, Miller B, Young A.

Department of Surgery, University of California Irvine College of Medicine.

We studied the efficacy of resuscitation with antioxidants in an animal model of hemorrhagic shock. Male Sprague-Dawley rats were anesthetized, and 27 mL/kg of blood was withdrawn from the carotid artery over 2 minutes. The animals remained in hemorrhagic shock for 45 minutes, followed by 1 hour of resuscitation. Experimental groups were as follows: 1) 15,000 u/kg superoxide dismutase (SOD) in 54 mL/kg lactated Ringer (LR); 2) 175,000 u/kg catalase (CAT) in LR; 3) 15,000 u/kg SOD+175,000 u/kg CAT in LR; 4) allopurinol in LR; 5) deferoxamine bound to pentafraction (DFO), 27 mL/kg; 6) pentafraction alone; and 7) LR alone. Compared with resuscitation with LR alone, SOD and allopurinol improved survival over 72 hours, P < 0.05. Survival with SOD+CAT was not different from LR alone. Deferoxamine bound to pentafraction did not increase survival over that with pentafraction alone. CAT had increased mortality compared to LR, P < 0.01. The efficacy of both SOD and allopurinol in decreasing mortality suggests the importance of superoxide radicals after hemorrhagic shock and resuscitation. These and other antioxidants are potential therapeutic agents in the clinical setting of trauma and hemorrhagic shock.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8256931&dopt=Abstract allopurinol Zyloprim