Allopurinol
The effect of allopurinol pretreatment before detorting testicular torsion.

Akgur FM, Kilinc K, Aktug T, Olguner M.

Department of Pediatric Surgery, Medical Faculty, Dokuz Eylul University, Izmir, Turkey.

The resumption of blood flow to organs following ischemia may cause a further increase in tissue damage through an increase in peroxidation of lipids in cell membranes. An experimental study was conducted to investigate the prevention of reperfusion injury after testicular torsion through changes in the lipid peroxide content of the testis. Adult male albino rats were divided into 11 groups, each containing 10 rats. One group served to determine base values of the lipid peroxide content of the testis and kidney; 3 groups were subjected to unilateral testicular torsion lasting 1, 3 and 5 hours; 3 groups were subjected to detorsion following torsion lasting 1, 3 and 5 hours; 3 groups were treated with allopurinol before detorsion following torsion lasting 1, 3 and 5 hours; and 1 group underwent sham operation as a control. Thiobarbituric acid reactive products of lipid peroxidation (TBAR) were assessed in testicular and renal tissues. Testicular torsion caused a significant increase in TBAR in the testis (p < 0.01), but not in the kidneys. Detorsion caused a further significant increase in testicular TBAR (p < 0.01). Pretreatment with allopurinol prevented this further increase (p < 0.01). It is concluded that, biochemically, reperfusion injury occurs in the testis following detorsion after testicular torsion of 720 degrees lasting as long as 5 hours. Pretreatment with allopurinol before detorsion prevents such reperfusion injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8189603&dopt=Abstract allopurinol Zyloprim



Allopurinol
The effect of allopurinol on experimental island skin flap survival under prolonged periods of arterial ischaemia.

Tamir G, Yaffe B, Pri-Chen S, Hauben DJ, Tsur H.

Department of Plastic Surgery, Beilinson Medical Center, Petah Tiqva, Israel.

The aim of this study was to assess the effect of allopurinol on rat groin flaps rendered ischaemic by selectively occluding the feeding femoral artery and reperfused by means of microsurgical anastomosis. For the establishment of the critical arterial ischaemia time, the femoral artery of 29 rat groin flaps isolated on the inferior epigastric pedicle was occluded for 10, 12 and 14 h. Following 12 h or more of ischaemia, 5.25% of the flaps survived, compared to 40% survival after 10 h (p = 0.04). In the second stage of the study, 34 rat groin flaps were subjected to arterial ischaemia for 12 h. Of these, 12 rats received allopurinol solution I.V. 30 min prior to reperfusion, 10 received the vehicle solution (control) and 12 underwent no treatment (control). After 7 days, survival of the groin flaps was observed in 41.7%, 0 and 8.3% of the groups, respectively (p = 0.0164). This study suggests that systemic administration of allopurinol has a beneficial effect on rat arterial ischaemic groin flaps and may prolong their critical ischaemia time.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8193850&dopt=Abstract allopurinol Zyloprim



Allopurinol
Nephrotoxicity induced by a single dose of adenine: effects of 4-aminopyrazolo[3,4-d]pyrimidine and allopurinol.

Minami T, Nakagawa H, Ichii M, Kadota E, Okazaki Y.

Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.

The effects of allopurinol and 4-aminopyrazolo[3,4-d]pyrimidine (4APP) on adenine-induced renal injury in mice were examined. Plasma urea nitrogen (UN) and creatinine levels increased after the oral administration of adenine to mice. However, plasma UN and creatinine levels decreased inversely with the dose of 4APP when a different dosage of 4APP was administered together with adenine. Yet 4APP did not have any effect on the UN or creatinine levels when 4APP was administered after adenine administration. Plasma UN and creatinine levels increased in the allopurinol-administered group as in the adenine-administered group. Moreover, from light microscopic observation by hematoxylin-eosin staining, microvacuolic changes in the proximal tubuli were detected in the mouse kidney in the adenine-administered group, and epithelial cell loss, degeneration and microvacuolic changes in the proximal tubuli were observed in the mouse kidney in the adenine-and-allopurinol-administered group. However, there were no changes in the proximal tubuli in the mouse kidney in the adenine-and-4APP-administered group. These findings suggested that 4APP inhibits the action of adenine in the mouse kidney.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8205116&dopt=Abstract allopurinol Zyloprim



Allopurinol
The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts.

Yang CS, Tsai PJ, Chou ST, Niu YL, Lai JS, Kuo JS.

Department of Medical Research, Taichung Veterans General Hospital, Taiwan, R.O.C.

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9101252&dopt=Abstract allopurinol Zyloprim