Allopurinol
Allopurinol-enhanced myocardial protection does not involve xanthine oxidase inhibition or purine salvage.

Chambers DJ, Takahashi A, Humphrey SM, Harvey DM, Hearse DJ.

Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London.

Isolated working rat hearts were subjected to aerobic perfusion (25 min), cardioplegic infusion (3 min), global ischemia (30 min at 37 degrees C) and reperfusion (35 min). Measurements of myocardial xanthine oxidase and dehydrogenase activity, together with various adenine nucleotides and metabolites, were made at defined stages of the protocol (n = 6/group). Allopurinol pretreatment (20 mg/kg body wt/day for 3 days) improved the postischemic recovery of cardiac function; thus, aortic flow (a representative index) recovered to 68.8 +/- 4.2% compared with 53.2 +/- 2.3% in untreated controls (p less than 0.05). In fresh tissue, allopurinol pretreatment inhibited xanthine dehydrogenase activity by 73.1% (from 11.9 +/- 0.5 to 3.2 +/- 0.8 mIU/g wet wt: p less than 0.05) and xanthine oxidase activity by 95.2% (from 8.3 +/- 1.2 to 0.4 +/- 0.2 mIU/g wet wt: p less than 0.05); however, this inhibition was not maintained during perfusion. During reperfusion, myocardial xanthine dehydrogenase and oxidase activity was reduced by 40-60% (p less than 0.05) in both allopurinol pretreated and control hearts. Tissue content of creatine phosphate, adenosine triphosphate and catabolites, NAD and inorganic phosphate were not different in allopurinol pretreated or control hearts during either ischemia or reperfusion. This study does not support the concept that allopurinol protects the rat heart during ischemia and reperfusion by inhibition of xanthine oxidase activity or by conservation of purines. It appears that allopurinol achieves its protective effects by some, as yet undefined, mechanism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1520248&dopt=Abstract allopurinol Zyloprim



Allopurinol
Role of oxygen free radicals in the etiology of pouchitis.

Levin KE, Pemberton JH, Phillips SF, Zinsmeister AR, Pezim ME.

Department of Surgery, Mayo Clinic Medical School, Rochester, Minnesota.

Transient mucosal ischemia may cause oxygen-derived free radical production by xanthine oxidase, precipitating pouchitis after ileal pouch-anal anastomosis. Our aim, therefore, was to determine the effect of allopurinol, a xanthine oxidase inhibitor, in patients with acute and chronic pouchitis. Acute pouchitis was characterized clinically by sporadic episodes of increased frequency and decreased viscosity of stools, hematochezia, fever, malaise, and pelvic pain, which resolved promptly with treatment. Chronic pouchitis patients required continuous treatment to remain asymptomatic and invariably developed the signs and symptoms of pouchitis within one week following cessation of therapy. Eight patients with acute pouchitis were treated with allopurinol (300 mg p.o. b.i.d.) during the episode. Fourteen patients with chronic pouchitis had their standard antibiotic therapy discontinued while still asymptomatic; they were then given allopurinol (300 mg p.o. b.i.d.) for 28 days. Acute pouchitis resolved promptly in four of eight patients. Seven of the 14 patients with chronic pouchitis responded completely with no recurrence of symptoms during treatment. Allopurinol either terminated an episode of acute pouchitis or prevented pouchitis from recurring in 50 percent of patients. These data support a role for mucosal ischemia and oxygen free radical production in the etiology of pouchitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1568395&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol-induced nephrotoxicity: protection by the antioxidant, butylated hydroxytoluene.

Ansari NH, Rajaraman S.

Department of Ophthalmology, Univeristy of Texas Medical Branch, Galveston 77550.

The present study was conducted to provide morphological evidence for allopurinol-induced nephrotoxicity in rats and its prevention by the antioxidant butylated hydroxytoluene (BHT). The kidneys of male Sprague Dawley rats fed a diet containing 0.3% allopurinol for 25 days exhibited a marked increase in the weight (2.5 times) as compared to the controls (without allopurinol). Upon microscopic examination, extensive tubulo-interstitial injury leading to structural damage was observed. Feeding BHT (0.4%) along with 0.3% allopurinol brought about a remarkable amelioration of the nephrotoxicity. The results indicate that usage of BHT along with the antiurecemic drug, allopurinol, may be helpful in improving the allopurinol-induced nephrotoxicity observed in some gout patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1570405&dopt=Abstract allopurinol Zyloprim



Allopurinol
Liver cirrhosis induced by carbon tetrachloride and the effect of superoxide dismutase and xanthine oxidase inhibitor treatment.

Dashti HM, al-Sayer H, Behbehani A, Madda J, Christenson JT.

Department of Surgery, Faculty of Medicine, Kuwait University, Safat.

Repeated administration of carbon tetrachloride (CCl4) induces liver cirrhosis, possibly because it involves the production of free radicals. In order to evaluate the effect of free radical scavengers such as superoxide dismutase (SOD) and allopurinol in the pathogenesis of liver cirrhosis, rats were subjected to repeated CCl4 administration with and without scavengers. Four groups of animals were studied: CCl4 plus SOD (group 1), CCl4 plus allopurinol (group 2), CCl4 alone (group 3) and olive oil (group 4, normal controls). Analysis of plasma and tissue concentrations of trace elements was performed and histopathological patterns were studied in all groups after 7 weeks of repeated intraperitoneal administration of the solutions. Plasma levels of zinc and selenium were significantly lower in all experimental groups, with reciprocal elevation of manganese and copper. Copper and manganese content in the liver tissue was significantly higher in all three experimental groups. The zinc content was elevated in groups receiving CCl4 alone (group 3) or with allopurinol (group 2). The liver selenium, however, was significantly lower in these two groups. The copper:zinc ratio for plasma was 0.78 in the control group, 1.6 in the CCl4 group, 1.3 in the allopurinol group and 1.5 in the SOD group. For liver tissue, the ratio was 0.07 for controls, 0.17 for CCl4, 0.11 for allopurinol and 0.28 for the SOD group. The changes in trace element content correlated with the severity of cellular damage observed microscopically in the liver. The higher the copper:zinc ratio, the more advanced and extensive was the microscopic evidence of liver injury after CCl4 challenge.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1573602&dopt=Abstract allopurinol Zyloprim



Allopurinol
Biological response of German cockroaches fed diets containing allopurinol.

Suiter DR, Koehler PG, Patterson RS.

Department of Entomology and Nematology, University of Florida, Gainesville.

The acceptability of dietary allopurinol to German cockroaches, Blattella germanica (L.), was assessed. In diet choice tests between rat chow with or without 0.1% w/w allopurinol there were no significant differences in nymphal development, feeding duration, visits or consumption. The LT50 of cockroaches fed a choice of diets was 3 weeks greater (7.88) than those fed non-choice a 0.1% allopurinol diet. Female cockroaches provided a choice of diets aborted a significantly greater percentage of their oothecae (98.6%) than those fed the untreated diet (1.7%). Choice arena tests of 2% allopurinol in rat chow significantly reduced cockroach populations compared with untreated controls. After 6 weeks, populations were reduced by approximately 50%, and 97% after 14 weeks. These results indicate that allopurinol is acceptable to B. germanica as a dietary supplement which could be used in baits for cockroach control.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1600230&dopt=Abstract allopurinol Zyloprim



Allopurinol
Dietary effects of allopurinol and sulfinpyrazone on development, survival, and reproduction of German cockroaches (Dictyoptera: Blattellidae).

Suiter DR, Koehler PC, Patterson RS.

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

Diets containing two gout medications, allopurinol and sulfinpyrazone, were fed ad libitum to first- or second-instar German cockroaches for 15 wk or until 100% mortality was reached. Cockroaches fed greater than or equal to 0.10% allopurinol diets weighed significantly less than those fed the control diet. Mortality of cockroaches fed diets containing greater than or equal to 0.05% allopurinol was significantly greater than those fed the control diet. The LT50 (6.1 wk) of cockroaches fed diets containing 0.10% allopurinol was significantly less than those fed any other diet containing allopurinol. LT50s and slopes were proportional and inversely related, respectively, to percentage of allopurinol in the diet. The addition of sulfinpyrazone to allopurinol diets minimally enhanced the blatticidal nature of the diets. Nymphs fed diets containing greater than or equal to 0.05% allopurinol experienced significant delays in adult emergence. Cockroaches fed greater than or equal to 0.01% allopurinol diets aborted a significantly greater percentage of their oothecae than those fed the 0.001% allopurinol or control diets. Hatched oothecae from cockroaches fed the 0.01% allopurinol diet had significantly fewer nymphs than those fed the 0.001% allopurinol or control diets. Percentage of oothecae aborted and number of nymphs per hatched ootheca from cockroaches fed a 2% sulfinpyrazone diet did not differ significantly from the control.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1607472&dopt=Abstract allopurinol Zyloprim