Allopurinol
D-Allose has a strong suppressive effect against ischemia/reperfusion injury: a comparative study with allopurinol and superoxide dismutase.

Hossain MA, Izuishi K, Tokuda M, Izumori K, Maeta H.

First Department of Surgery, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, 761-0793, Kagawa, Japan.

BACKGROUND/PURPOSE: D-Allose, a rare sugar, is one of the potent inhibitors of ischemia/reperfusion injury of the rat liver. To investigate the potency of this powerful agent we examined its effect against ischemia/reperfusion injury and compared it to that of allopurinol and superoxide dismutase. METHODS. Male Lewis rats were given water ad libitum preoperatively for 12 h and anesthetized by isoflurane inhalation anesthesia. Drugs were administered through a polyethylene catheter inserted into the portal vein for 2 h (D-allose), 10 min (allopurinol), or 5 min (superoxide dismutase) before ischemia, and the livers were then subjected to 70% ischemia, induced by crossclamping the vessels to the lateral and median lobes of the liver for 90 min. Rats were divided into four groups: group 1, pretreated with vehicle (normal saline); group 2, treated with D-allose; group 3, treated with allopurinol; and group 4, treated with superoxide dismutase. The effects of the drugs were evaluated by liver hemodynamics, neutrophil count, myeloperoxidase, liver enzymes, and histological studies. RESULTS. D-Allose improved liver hemodynamics (P < 0.001) and postischemic animal survival (P < 0.05) significantly compared with the control group and nonsignificantly compared with the allopurinol and superoxide dismutase groups. Myeloperoxidase activity in the postischemic liver tissue was decreased significantly (P < 0.05) by D-allose compared with all other treatment and control groups. Neutrophil count was also significantly (P < 0.05) decreased in the D-allose group compared with than that in the control group, as well as the superoxide dismutase group. Only D-allose produced a statistically significant decrease in the level of liver enzymes, compared with levels in the control group. CONCLUSIONS. The moderately protective effect of D-allose, which caused no clinical side effects, is encouraging. D-Allose had the best protective effect against neutrophil-related postischemic injury of the liver tissue, followed by allopurinol and superoxide dismutase. However, a more extensive study is needed to ensure the effects as well as the mechanisms of the effect of this rare sugar. Copyright 2004 Springer-Verlag

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15235891&dopt=Abstract allopurinol Zyloprim



Allopurinol
Limitation of apoptotic changes in renal tubular cell injury induced by hyperoxaluria.

Sarica K, Erbagci A, Yagci F, Bakir K, Erturhan S, Ucak R.

Department of Urology, Sahinbey Medical Center, University of Gaziantep, Medical School, 27070 Kolejtepe/ Gaziantep, Turkey. kemalsarica superonline.com

Renal tubular epithelium is the major target for oxalate induced injury, and sustained hyperoxaluria together with CaOx crystal formation/deposition may induce renal tubular cell damage and/or dysfunction. This may express itself in cell apoptosis. To evaluate the possible protective effects of certain agents (vitamin E, potassium citrate, allopurinol, verapamil and MgOH) on the presence and the severity of apoptotic changes caused by hyperoxaluria on renal tubular epithelium, an experimental study in rabbits was performed. Seventy rabbits were divided into seven different groups (each group n = 10): in group I severe hyperoxaluria was induced by continuous ethylene glycol (0.75%) administration started on day 0 and completed on day 14. Histologic alterations including crystal formation together with apoptotic changes (by using the TUNEL method) were evaluated on days 21 and 42, respectively. In the remaining experimental groups (groups II-VI), animals received some agents in addition to the induction of hyperoxaluria in an attempt to limit apoptotic changes. Group VII) animals constituted the controls. Kidneys were examined histopathologically under light microscopy for the presence and degree of crystal deposition in the tubular lumen. The percentage of apoptotic nuclei in the control group was significantly different from the other group animals (2.9-2.4%) in all study phases (P < 0.05). Apart from potassium citrate and allopurinol, the other medications seemed to prevent or limit the formation of apoptotic changes in renal tubular epithelium during the early period (day 21). The percentage of positively stained nuclei in animals undergoing potassium citrate medication ranged from 24.3% to 28.6%, with an average of 27.1%. This was 18.4% in animals receiving allopurinol. On the other hand, animals receiving magnesium hydroxide (MgOH), verapamil and vitamin E demonstrated limited apoptotic changes (11.2, 9.7, 8.7%, respectively) during this phase(P < 0.05). In the long-term (day 42), the animals receiving allopurinol and vitamin E showed a decrease in the percentage of the positively stained nuclei (13.5% and 8.3%, respectively). Animals in the other groups showed an increase in the number and percentage of apoptotic cells. Although, there was a significant decrease in the mean values of apoptosis in animals receiving vitamin E (8.7%-8.3%) and allopurinol (18.4%-13.5%) (P < 0.05), animals on verapamil, MgOH and potassium citrate medication had an increase in these values or the change was not found to be significant. In the light of our findings and results from the literature, it is clear that that both hyperoxaluria and CaOx crystals may be injurious to renal epithelial cells. Apoptotic changes observed in renal tubular epithelial cells induced by massive hyperoxaluria might result in cell degradation and may play a role in the pathologic course of urolithiasis. Again, as demonstrated in our study, the limitation of both crystal deposition and apoptotic changes might be instituted by some antioxidant agents as well as urinary inhibitors. Clinical application of such agents in the prophylaxis of stone disease might limit the formation of urinary calculi, especially in recurrent stone formers. Copyright 2004 Springer-Verlag

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15249986&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading in mice.

Matuszczak Y, Arbogast S, Reid MB.

Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.

INTRODUCTION: Prolonged mechanical unloading induces skeletal muscle weakness, a major problem following extended bed rest or spaceflight. Antioxidants are reported to partially inhibit the weakness caused by limb immobilization. The current study tested allopurinol, a xanthine oxidase inhibitor with antioxidant properties, for its capacity to protect the function of unloaded antigravity muscles. METHODS: Adult mice conditioned by 12 d of hindlimb suspension, with or without allopurinol 50 mg x kg(-1) x d(-1), were compared with freely ambulating controls. Animals were anesthetized and soleus muscles were isolated for ex vivo analyses. RESULTS: Relative to control muscles, unloading decreased soleus weight (-44%; p < 0.05) and cross-sectional area (-38%; p < 0.05), increased cytosolic oxidant activity (-46%; p < 0.01), decreased absolute tetanic force (e.g., -64% at 250 Hz; p < 0.001 ) and force/area (-35%; p < 0.01), and increased passive compliance of the unstimulated muscle (p < 0.05). Allopurinol administration blunted the effects of unloading, partially inhibiting losses of absolute force (p < 0.05) and force/area (p < 0.05) without affecting muscle atrophy. The drug also blunted compliance changes in the passive muscle (p < 0.05). DISCUSSION: Allopurinol does not inhibit atrophy of skeletal muscle caused by prolonged unloading. However, allopurinol does lessen the contractile dysfunction caused by unloading, an action that may have potential benefit for astronauts and bedridden individuals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15267079&dopt=Abstract allopurinol Zyloprim



Allopurinol
Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims.

Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M.

Research and Data Services Group, Ingenix Pharmaceutical Services, Eden Prairie, Minnesota 55344, USA.

OBJECTIVE: Poor compliance with gout medications has been recognized, but seldom studied. We investigated compliance with allopurinol among managed care enrollees suspected to have gout. METHODS: This was a retrospective, administrative claims-based analysis of patients with gout. Compliance with allopurinol was measured using prescription-fill dates and days-supplied amounts. Compliance was defined for each prescription period as the presumed use of allopurinol on at least 80% of the days of that period. RESULTS: Of 9482 patients identified, 65.9% filled at least one prescription for allopurinol during the 24 month followup period; 10.4% of allopurinol users filled one prescription and then discontinued use. Of the remaining patients, 13.7% never achieved compliance with therapy; 18% were compliant throughout the entire followup period. Patients were compliant with therapy for an average of 56% of their treatment periods and noncompliant for an average of 44%. In multivariate analysis, male sex was associated with decreased compliance (p < 0.01), although the effect was mitigated by increasing age. For subjects of both sexes, increasing age was associated with increased compliance (p < 0.05). CONCLUSION: Compliance with allopurinol in this population was low. Because untreated gouty arthritis can lead to serious adverse outcomes (such as recurrent gouty arthritis, chronic gouty arthropathy, tophi, and urolithiasis) that are usually avoidable with antihyperuricemic therapy, efforts to achieve better compliance are warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15290738&dopt=Abstract allopurinol Zyloprim



Allopurinol
Beneficial effects of melatonin compared with allopurinol in experimental testicular torsion.

Abasiyanik A, Dagdonderen L.

Department of Pediatric Surgery, Selcuk University, Medical Faculty, Konya, Turkey.

BACKGROUND/PURPOSE: Several antioxidant agents such as allopurinol have been used to prevent ischemia-reperfusion (I/R) injury-induced tissue damage after experimental testicular torsion so far. The current study was designed to determine the effect of melatonin, which is a potent antioxidant agent, in preventing testicular damage following torsion. METHODS: Sixty prepubertal male Wistar-Albino rats were divided into 5 groups: control (C), torsion (T), torsion plus detorsion (TD), torsion plus allopurinol (200 mg/kg) plus detorsion (A), and torsion plus melatonin (50 mg/kg) plus detorsion (M). Left testes were rotated 720 degrees for 6 hours. The torsed testes were detorsed. Detorsion time was 6 hours. In all groups, left orchiectomies were performed to determine the tissue levels of malondialdehyde (MDA) and histopathologic changes. Blood samples were taken to measure serum creatine phosphokinase (CPK) levels. The results were analyzed statistically. RESULTS: Serum CPK levels of groups A and M were found to be significantly lower than groups T and TD (P <.05). Tissue MDA levels in group M were statistically different from groups T and TD (P <.05). However, in groups A and T, MDA levels were similar (P >.05). The highest histologic grade was determined in group TD (3.8 +/- 0.5). Histologic grade of group M was significantly lower than group TD (P <.001), but there was no histologic difference between testes of groups A and TD (P >.05). CONCLUSIONS: These results have shown that melatonin treatment prevents I/R injury both biochemically and histopathologically, whereas allopurinol treatment prevents it only biochemically in experimental testicular torsion. Melatonin is a potent antioxidant agent more effective than allopurinol in preventing testicular I/R injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15300535&dopt=Abstract allopurinol Zyloprim



Allopurinol
Elevated serum homocysteine levels for gouty patients.

Cheng TT, Lai HM, Chang HW, Luo SF.

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan, ROC.

Our objective was to analyze serum total homocysteine (tHcy) levels for gouty patients and to study whether there are any level changes following treatment with allopurinol. We enrolled 90 male participants including patients with primary gout ( n=51) and community-based healthy controls ( n=39). Fasting tHcy levels were determined for all subjects and repeat measurements performed for 29 patients following treatment with allopurinol. The results revealed that gouty patients exhibited significantly greater serum tHcy levels (12.10+/-3.19 micromol/l) than healthy controls did (9.96+/-2.16 micromol/l) ( p=0.0003), although there was no obvious difference between the pre-allopurinol treatment group (12.54+/-3.31 micromol/l) and its post-treatment analogue (11.90+/-4.68 micromol/l) ( n=29, p=0.33). Elevated serum levels of tHcy were noted for this cohort of male gouty patients as compared to healthy controls, and these tHcy levels did not appear to change substantially following treatment with allopurinol. Although the pathogenesis of hyperhomocysteinemia for gouty patients still remains somewhat obscure, this study suggests that tHcy levels cannot be effectively modulated by treatment with allopurinol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15378395&dopt=Abstract allopurinol Zyloprim