Allopurinol
Four consecutive renal transplantations in a patient with adenine phosphoribosyltransferase deficiency.

Eller P, Rosenkranz AR, Mark W, Theurl I, Laufer J, Lhotta K.

Department of Internal Medicine, Clinical Nephrology Division, Innsbruck University Hospital, Innsbruck, Austria.

We report a patient with complete adenine phosphoribosyltransferase deficiency and urolithiasis, in whom 4 consecutive cadaveric renal transplantations were performed; 2,8-dihydroxyadenine crystal nephropathy recurred within weeks in the first and second graft when the patient was not treated with allopurinol immediately after transplantation. In the third graft, recurrence of disease could be prevented by immediate allopurinol treatment. This graft was lost due to chronic allograft nephropathy without significant crystal deposition. After a fourth transplantation, again without initial allopurinol, the disease recurred following an initial vascular rejection. Addition of allopurinol significantly improved renal function of the 2nd and 4th graft. This case indicates that outcome of renal transplantation in patients with adenine phosphoribosyltransferase deficiency critically depends on immediate postoperative pharmacotherapy with allopurinol, which is able to prevent 2,8-dihydroxyadenine nephropathy in the graft. Furthermore, rapid recurrence of disease without allopurinol seems to be triggered by delayed graft function and acute rejection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15077874&dopt=Abstract allopurinol Zyloprim



Allopurinol
Improved survival in a replantation model containing ischemic muscle.

Concannon MJ, Dooley TW, Puckett CL.

Division of Plastic & Reconstructive Surgery, University of Missouri Health Sciences Center, Columbia 65212.

The effectiveness of superoxide dismutase and allopurinol was evaluated in preventing reperfusion injury in Sprague-Dawley rats utilizing a limb replantation model after 6 hours of warm ischemia. Immediately prior to reperfusion of the replanted limb the animals received (intravenously) either a single bolus of superoxide dismutase (16,000 units/kg), a single bolus of allopurinol (45 mg/kg), both agents, or only control solutions. In the rats that received only control solutions, 30% of the limbs survived the ischemic insult. The group that received both superoxide dismutase and allopurinol had a 75% limb survival (P = 0.005). The animals that had only superoxide dismutase or allopurinol had 58% and 60% of the replanted limbs survive, respectively. This study suggests that the administration of superoxide dismutase and allopurinol may be helpful in the prevention of reperfusion injury in skeletal muscle in an acute injury setting (without pretreatment) and may thereby improve limb salvage after a significant ischemic period.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1990244&dopt=Abstract allopurinol Zyloprim



Allopurinol
Renal tubular alteration by crystalluria in stone disease-an experimental study by means of MDCK cells.

Lahme S, Feil G, Strohmaier WL, Bichler KH, Stenzl A.

Department of Urology, University of Tubingen, Tubingen, Germany. sven.lahme med.uni-tuebingen.de

OBJECTIVES: Physicochemical properties of urine do not explain the formation of urinary stones. Clinical findings and results of animal experiments suggest that alteration to the renal tubular cell plays a key role in the initiation of urinary stone formation. It is not clear whether this is a primarily intracellular alteration of metabolic origin which, after lysis of the renal tubular cell in the lumen, presents a nucleus for the formation of concretions, or whether in the lumen it is tubular cell damage induced by crystalluria that triggers the formation of urinary stones. MATERIALS AND METHOD: Using Madin-Darby canine kidney cells, the influence of crystalluria on the renal tubular cell was tested in cell cultures. The influence of parathyroid hormone, vitamin D(3), oxalate and calcium concentrations and the extent to which these processes can be inhibited by allopurinol and selenium were investigated. RESULTS: Calcium oxalate monohydrate crystals produced reproducible damage to the renal tubular cell which was independent of parathyroid hormone and vitamin D(3). The crystalluria-induced effects were unrelated to the oxalate and calcium concentration or the pH. Allopurinol and selenium were able to inhibit the processes. CONCLUSION: The results indicate secondary involvement of the renal tubular cell in lithogenesis as a result of luminal alteration caused by calcium oxalate crystals. Mechanical damage and interaction between crystal and tubular cell lead to the apposition of crystals. The nephroprotective effect of allopurinol and selenium as antioxidants might explain the benefit of allopurinol found clinically in terms of stone metaphylaxis. Copyright 2004 S. Karger AG, Basel

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Allopurinol
Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

Trachtman H, Valderrama E, Futterweit S.

Department of Pediatrics Division of Nephrology, Schneider Children's Hospital, New Hyde Park, NY 11042.

Hyperuricemia is present in 20-40% of pediatric and adult patients with essential hypertension. This metabolic abnormality may represent an additional risk factor for the development of cardiovascular disease. Therefore, we performed the following studies to determine 1) whether hyperuricemia is more prevalent in the spontaneously hypertensive rat (SHR) and 2) whether allopurinol treatment has a beneficial effect on the development of hypertension in this strain, based on its capacity to lower the serum uric acid concentration and to act as an antioxidant agent. SHR and control Wistar-Kyoto (WKY) rats were assigned to two groups, one given tap water to drink and the other provided water containing allopurinol (400 mg/l) to furnish an approximate daily dose equal to 100 mg/kg body wt. This treatment was maintained for 15 weeks. The serum uric acid levels were similar in untreated SHR and WKY rats (1.85 +/- 0.10 versus 1.66 +/- 0.14 mg/dl; p = 0.28). In the control WKY rat strain, allopurinol therapy did not adversely affect weight gain or hematocrit and did not cause an increase in mortality. It resulted in a moderate decrement in kidney function (creatinine clearance: allopurinol-treated group 0.32 +/- 0.09 versus control group 0.46 +/- 0.04 ml/min/100 g body wt, in conjunction with mild-to-moderate tubulointerstitial inflammation (allopurinol-treated group 0.9 +/- 0.4 versus control group 0).(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1991652&dopt=Abstract allopurinol Zyloprim



Allopurinol
Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia.

Betz AL, Randall J, Martz D.

Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0570.

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1996699&dopt=Abstract allopurinol Zyloprim



Allopurinol
The effects of verapamil vs. allopurinol on intestinal ischemia/reperfusion injury in rats. "An experimental study".

Kulah B, Besler HT, Akdag M, Oruc T, Altinok G, Kulacoglu H, Ozmen MM, Coskun F.

Ankara Numune Teaching and Research Hospital 3rd Surgical Clinic, Turkey.

BACKGROUND/AIMS: Although studies have reported that xanthine oxidase inhibitors or calcium channel blockers attenuate the ischemia-reperfusion injury in several organ systems, no comparative study exists on the significance of each of these pathways. To study this, in anesthetized Wistar Albino rats, a surgical model for intestinal ischemia-reperfusion injury was employed. METHODOLOGY: In experimental animals, after laparotomy, the superior mesenteric artery was occluded for 30 min, followed by a 2-h period of reperfusion; control rats underwent only a sham laparotomy procedure. One group of experimental animals was pretreated intraperitoneally with the calcium channel blocker verapamil (0.3 mg/kg), another group with the xanthine oxidase inhibitor allopurinol (100 mg/kg), the third group received no pretreatment. Plasma lactate, malondialdehyde and glutathione levels as well as intestinal tissue malondialdehyde and glutathione levels were measured to assess for possible protective effects. Histologic evaluation of the extent of injury was also performed. RESULTS: Irreversible tissue damage was depicted in the untreated group, and partially in the allopurinol pretreatment group by histologic examination. Ischemia-reperfusion injury was reversible in the verapamil group. The laboratory results also supported these findings. CONCLUSIONS: Protective effects of verapamil on ischemia-reperfusion injury have been found to be significantly (p<0.0001) more effective compared to allopurinol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15086169&dopt=Abstract allopurinol Zyloprim